1.Newly formulated Tadalafil tablets alleviates liver fibrosis in mice by inhibiting activation of hepatic stellate cells
Wen-bin FENG ; Jian-qin YANG ; Li-mei LI ; Jia-xiu LEI ; Fan LIU ; Zi-jian ZHAO ; Yun-ping MU ; Fang-hong LI
Chinese Pharmacological Bulletin 2025;41(2):290-297
Aim To investigate the therapeutic effect of newly formulated Tadalafil tablets on liver fibrosis in mice induced by carbon tetrachloride(CCl4)and its impact on the activation of hepatic stellate cells(HSCs).Methods Liver fibrosis model was estab-lished by intraperitoneally injecting 20%CCl4 corn oil solution twice a week for eight weeks.After four weeks of modeling,the treatment group was administered ei-ther the newly formulated Tadalafil tablets(1.0 mg·kg-1)or the Cialis(2.5 mg·kg-1)via gavage for the remaining four weeks.We assessed the effects of Tadalafil on collagen deposition,tissue structural dam-age,and HSCs activation markers in the fibrotic liver of mice using serum biochemical analysis,histopathologi-cal staining,and Western blotting following the treat-ment period.LX-2 cells were cultured and treated with tadalafil after TGF β1 stimulation,and the effects of tadalafil on LX-2 cell activation were assessed via Western blot.Results Compared to the normal mice,the model group mice exhibited a significantly higher liver-specific index,increased liver function indicators,and notable hepatocyte necrosis.Additionally,liver lobules were damaged,accompanied by severe infiltra-tion of inflammatory cells.Both smooth muscle actin(α-SMA)and fibronectin(Fn)were elevated,serving as markers of HSCs activation.As a result of treatment with the newly formulated Tadalafil tablets,liver tissue damage was significantly reduced,transaminase levels decreased,necrosis and inflammatory cell infiltration were reduced,and collagen fiber deposition was allevia-ted,and α-SMA and Fn expression was reduced.It was worth noting that low-dose newly formulated Tadalafil tablets were found to be as effective as high-dose Cia-lis.In a cellular model,Tadalafil significantly inhibited the activation of LX-2 cells and reduced the expression of proteins related to cell activation.Conclusions The newly formulated Tadalafil tablets can significantly inhibit HSCs activation,reduce extracellular matrix(ECM)deposition,improve liver fibrosis and liver function damage caused by CCl4.This new formulation offers a significant advantage over Cialis in terms of ef-fectiveness,with a lower effective dose.
2.Comparative Experimental Study of Nd∶YAG Laser Ablation of Fresh Isolated Pig Liver
Ruo-yu LIU ; Mu YUAN ; Hao LI ; Zi-yi ZHU ; Yu-lin TAN
Progress in Modern Biomedicine 2025;25(10):1613-1619,1657
Objective:To compare the characteristics and temperature changes of single and double fiber Nd∶YAG laser in fresh isolated pig liver,and to provide reference for clinical ablation treatment.Methods:Single-needle single-point and double-needle double-point ablations were perf ormed on fresh isolated pig livers using a 5 W power laser,and the morphology,range,and surrounding temperature changes of the ablation lesions caused by the two in vitro liver tissues were observed.Results:The ablation lesions were divided into carbonized area,necrotic area and deformed area from inside to outside.The carbonized area in the center of the ablation lesion in the double-fiber group was larger and the cell necrosis was more thorough.The aspect ratio(LD/TD)of the laser ablation lesion in the single-fiber group was larger than that in the double fiber group(P<0.001).The transverse diameter(TD)and volume(V)of the ablation lesion in the double-fiber group were larger than those in the single-fiber group(P<0.001).There was no significant difference in the longitudinal diameter(LD)of the ablation lesion between the double-fiber group and the single-fiber group(P>0.05).There was no significant difference in the temperature of 20 s,40 s and 60 s at 5 mm and 10 mm beside the ablation center between the two groups(all P>0.05).Conclusion:Under the condition of 5 W,the temperature changes around the single and double fiber ablation are similar.The single fiber is suitable for small tumor ablation,and the double fiber ablation range is larger,which can be used for one-time full coverage ablation of larger cancer nodules.
3.The therapeutic effects of newly formulated Tadalafil tablets on rats with pulmonary fibrosis through promoting histone acetylation
Xiao-qing LIU ; Jie GAO ; Yu-heng LIAO ; Jia-xiu LEI ; Zheng-gang ZHAO ; Fang-hong LI ; Yun-ping MU ; Zi-jian ZHAO
Chinese Pharmacological Bulletin 2025;41(11):2143-2150
Aim To investigate the therapeutic effects of a newly developed Tadalafil tablet on pulmonary fi-brosis induced by paraquat(PQ)in rats,as well as its impact on histone acetylation levels in epithelial cells.Methods SD rats were randomly divided into four groups:the control group(control),the model group(PQ),the Tadalafil new tablet treatment group(N-Tad,1 mg·kg-1),and the positive control drug treatment group(Cialis,5 mg·kg-1).The model group and treatment group rats were intraperitoneally injected with PQ(30 mg·kg-1).Two hours after the initial treatment,the rats in the treatment group re-ceived N-Tad or Cialis via gavage,while the control and model groups were administered an equal volume of physiological saline by gavage once daily for 28 days.The weight gain rate and lung tissue index for each group of rats were calculated.Additionally,the effects of N-Tad treatment on lung tissue structural damage and collagen deposition in rats with PQ-in-duced pulmonary fibrosis were observed using HE stai-ning,Masson trichrome staining,and immunohisto-chemical techniques.By employing the Western blot technique,the effects of Tadalafil intervention on the expression of the epithelial marker E-cadherin(E-Cad),the stromal marker fibronectin(Fn),and the histone acetylation marker acetylated histones(Ac-his-tones)in A549 cells were observed.Results Com-pared to the control group,rats with PQ-induced pul-monary fibrosis exhibited a significant decrease in the rate of body weight growth,an increase in lung tissue index(P<0.05),and a notable increase in the expression and distribution of the fibrosis marker alpha-smooth muscle actin(α-SMA)in lung tissue.The structure of the lung tissue was disrupted,accompanied by the deposition of interstitial collagen fibers.Both N-Tad and Cialis treatments could significantly enhance the rate of weight gain,decrease the lung tissue index,inhibit the expression of α-SMA,and reduce the depo-sition of interstitial collagen in the lung tissue of rats with pulmonary fibrosis.Notably,low-dose N-Tad treatment was comparable to high-dose Cialis treat-ment.At the cellular level,Tadalafil significantly in-hibited the high expression of Fn induced by transfor-ming growth factor beta 1(TGF-β1)in A549 cells.It also upregulated the expression of E-cadherin and sig-nificantly increased the levels of acetylated histones(P<0.05).Conclusions N-Tad promotes histone acetylation in alveolar epithelial cells,significantly in-hibits epithelial-mesenchymal transition,increases E-cadherin expression,and improves lung tissue structur-al damage and collagen deposition caused by PQ.Ad-ditionally,it offers the advantage of a lower effective dose compared to Cialis,providing a new option for the treatment of pulmonary fibrosis.
4.The therapeutic effects of newly formulated Tadalafil tablets on rats with pulmonary fibrosis through promoting histone acetylation
Xiao-qing LIU ; Jie GAO ; Yu-heng LIAO ; Jia-xiu LEI ; Zheng-gang ZHAO ; Fang-hong LI ; Yun-ping MU ; Zi-jian ZHAO
Chinese Pharmacological Bulletin 2025;41(11):2143-2150
Aim To investigate the therapeutic effects of a newly developed Tadalafil tablet on pulmonary fi-brosis induced by paraquat(PQ)in rats,as well as its impact on histone acetylation levels in epithelial cells.Methods SD rats were randomly divided into four groups:the control group(control),the model group(PQ),the Tadalafil new tablet treatment group(N-Tad,1 mg·kg-1),and the positive control drug treatment group(Cialis,5 mg·kg-1).The model group and treatment group rats were intraperitoneally injected with PQ(30 mg·kg-1).Two hours after the initial treatment,the rats in the treatment group re-ceived N-Tad or Cialis via gavage,while the control and model groups were administered an equal volume of physiological saline by gavage once daily for 28 days.The weight gain rate and lung tissue index for each group of rats were calculated.Additionally,the effects of N-Tad treatment on lung tissue structural damage and collagen deposition in rats with PQ-in-duced pulmonary fibrosis were observed using HE stai-ning,Masson trichrome staining,and immunohisto-chemical techniques.By employing the Western blot technique,the effects of Tadalafil intervention on the expression of the epithelial marker E-cadherin(E-Cad),the stromal marker fibronectin(Fn),and the histone acetylation marker acetylated histones(Ac-his-tones)in A549 cells were observed.Results Com-pared to the control group,rats with PQ-induced pul-monary fibrosis exhibited a significant decrease in the rate of body weight growth,an increase in lung tissue index(P<0.05),and a notable increase in the expression and distribution of the fibrosis marker alpha-smooth muscle actin(α-SMA)in lung tissue.The structure of the lung tissue was disrupted,accompanied by the deposition of interstitial collagen fibers.Both N-Tad and Cialis treatments could significantly enhance the rate of weight gain,decrease the lung tissue index,inhibit the expression of α-SMA,and reduce the depo-sition of interstitial collagen in the lung tissue of rats with pulmonary fibrosis.Notably,low-dose N-Tad treatment was comparable to high-dose Cialis treat-ment.At the cellular level,Tadalafil significantly in-hibited the high expression of Fn induced by transfor-ming growth factor beta 1(TGF-β1)in A549 cells.It also upregulated the expression of E-cadherin and sig-nificantly increased the levels of acetylated histones(P<0.05).Conclusions N-Tad promotes histone acetylation in alveolar epithelial cells,significantly in-hibits epithelial-mesenchymal transition,increases E-cadherin expression,and improves lung tissue structur-al damage and collagen deposition caused by PQ.Ad-ditionally,it offers the advantage of a lower effective dose compared to Cialis,providing a new option for the treatment of pulmonary fibrosis.
5.Comparative Experimental Study of Nd∶YAG Laser Ablation of Fresh Isolated Pig Liver
Ruo-yu LIU ; Mu YUAN ; Hao LI ; Zi-yi ZHU ; Yu-lin TAN
Progress in Modern Biomedicine 2025;25(10):1613-1619,1657
Objective:To compare the characteristics and temperature changes of single and double fiber Nd∶YAG laser in fresh isolated pig liver,and to provide reference for clinical ablation treatment.Methods:Single-needle single-point and double-needle double-point ablations were perf ormed on fresh isolated pig livers using a 5 W power laser,and the morphology,range,and surrounding temperature changes of the ablation lesions caused by the two in vitro liver tissues were observed.Results:The ablation lesions were divided into carbonized area,necrotic area and deformed area from inside to outside.The carbonized area in the center of the ablation lesion in the double-fiber group was larger and the cell necrosis was more thorough.The aspect ratio(LD/TD)of the laser ablation lesion in the single-fiber group was larger than that in the double fiber group(P<0.001).The transverse diameter(TD)and volume(V)of the ablation lesion in the double-fiber group were larger than those in the single-fiber group(P<0.001).There was no significant difference in the longitudinal diameter(LD)of the ablation lesion between the double-fiber group and the single-fiber group(P>0.05).There was no significant difference in the temperature of 20 s,40 s and 60 s at 5 mm and 10 mm beside the ablation center between the two groups(all P>0.05).Conclusion:Under the condition of 5 W,the temperature changes around the single and double fiber ablation are similar.The single fiber is suitable for small tumor ablation,and the double fiber ablation range is larger,which can be used for one-time full coverage ablation of larger cancer nodules.
6.Newly formulated Tadalafil tablets alleviates liver fibrosis in mice by inhibiting activation of hepatic stellate cells
Wen-bin FENG ; Jian-qin YANG ; Li-mei LI ; Jia-xiu LEI ; Fan LIU ; Zi-jian ZHAO ; Yun-ping MU ; Fang-hong LI
Chinese Pharmacological Bulletin 2025;41(2):290-297
Aim To investigate the therapeutic effect of newly formulated Tadalafil tablets on liver fibrosis in mice induced by carbon tetrachloride(CCl4)and its impact on the activation of hepatic stellate cells(HSCs).Methods Liver fibrosis model was estab-lished by intraperitoneally injecting 20%CCl4 corn oil solution twice a week for eight weeks.After four weeks of modeling,the treatment group was administered ei-ther the newly formulated Tadalafil tablets(1.0 mg·kg-1)or the Cialis(2.5 mg·kg-1)via gavage for the remaining four weeks.We assessed the effects of Tadalafil on collagen deposition,tissue structural dam-age,and HSCs activation markers in the fibrotic liver of mice using serum biochemical analysis,histopathologi-cal staining,and Western blotting following the treat-ment period.LX-2 cells were cultured and treated with tadalafil after TGF β1 stimulation,and the effects of tadalafil on LX-2 cell activation were assessed via Western blot.Results Compared to the normal mice,the model group mice exhibited a significantly higher liver-specific index,increased liver function indicators,and notable hepatocyte necrosis.Additionally,liver lobules were damaged,accompanied by severe infiltra-tion of inflammatory cells.Both smooth muscle actin(α-SMA)and fibronectin(Fn)were elevated,serving as markers of HSCs activation.As a result of treatment with the newly formulated Tadalafil tablets,liver tissue damage was significantly reduced,transaminase levels decreased,necrosis and inflammatory cell infiltration were reduced,and collagen fiber deposition was allevia-ted,and α-SMA and Fn expression was reduced.It was worth noting that low-dose newly formulated Tadalafil tablets were found to be as effective as high-dose Cia-lis.In a cellular model,Tadalafil significantly inhibited the activation of LX-2 cells and reduced the expression of proteins related to cell activation.Conclusions The newly formulated Tadalafil tablets can significantly inhibit HSCs activation,reduce extracellular matrix(ECM)deposition,improve liver fibrosis and liver function damage caused by CCl4.This new formulation offers a significant advantage over Cialis in terms of ef-fectiveness,with a lower effective dose.
7.Application of intra-articular graft length measurement in total anterior cruciate ligament reconstruction
Shi-Guo GONG ; Rong-Hui XIE ; Jian-Yang WANG ; Mu-Zi LIU
China Journal of Orthopaedics and Traumatology 2024;37(7):655-663
Objective To investigate the clinical efficacy of arthroscopic measurement of intra-articular graft length in the application of total internal reconstruction of the anterior cruciate ligament(ACL).Methods The 60 patients with ACL injury treated between January 2020 and January 2022 were retrospectively analyzed.There were 37 males and 23 females,aged from 22 to 44 years.According to the different surgical methods,they were divided into two groups:conventional surgery group(conventional group)and pull-line measurement group(measurement group),with 30 cases in each group.In the conventional group,there were 20 males and 10 females,with an average age of(30.00±3.95)years old;the body mass index(BMI)was(22.58±1.41)kg·m-2;there were 9 cases on the left side and 21 cases on the right side;the time from injury to operation was(3.00±1.35)days.In the measurement group,there were 17 males and 13 females,with an average of(32.00±4.29)years;BMI was(23.29±1.39)kg·m-2;there were 12 cases on the left side and 18 cases on the right side;the time from injury to oper-ation was(3.00±1.27)days.The clinical data of the patients before surgery,6 months after surgery and 12 months after surgery were collected and recorded.The clinical efficacy of the two methods was compared in terms of postoperative VAS,KOOS,Lysholm score,IKDC score,knee stability(Lachman test,anterior drawer test and axial shift test),the degree of widening of bone tunnel diameter measured by CT at different stages of the postoperative period and MRI scoring system.Results At 12 months after surgery,the VAS of the measurement group was lower than that of the conventional group(P<0.001).At 12 months after surgery,KOOS scores in the measurement group were higher than those in the conventional group,and there were statistical-ly significant differences in all scores except symptom scores(P<0.05).Six months after operation,Lysholm total score and IKDC total score in the measurement group were higher than those in the conventional group,and the difference was statistically signifi-cant(P<0.05).At 12 months after surgery,knee stability tests were performed,and the differences between the Lachman test,anterior drawer test and axial shift test measurement group and the conventional group were not statistically significant(P>0.05).However,overall knee instability analysis showed that the knee stability of the measurement group was better than that of the con-trol group,and the difference between the groups was statistically significant(P=0.038).The imaging assessment of patients in both groups at 6 months after surgery showed that the widening of tendon tunnel diameter in both femur and tibia was reduced in the measurement group compared with the conventional group after surgery,and the difference was statistically significant(P<0.05);MRI scores were higher in all patients in the measurement group those in the conventional group,at 6 months and 12 months agter surgery(P<0.05).Conclusion Arthroscopic measurement of intra-articular cavity graft length in total internal technique for ACL reconstruction,high tendon utilization,good stability,the knee joint function has recovered satisfactorily within one year,and the therapeutic effect is affirmed.
8.Application characteristics and modern research progress of "bone-approaching" acupuncture.
De-Hui ZOU ; Kai-Xin FENG ; Hong-Wen LIANG ; Xu-Hao TANG ; Shan ZHAO ; Zi-Jian QIU ; Peng-Yong BAI ; Jia-Mu LIU ; Tong LIU
Chinese Acupuncture & Moxibustion 2023;43(9):1094-1098
The paper explores the evolution of "bone-approaching" acupuncture, its effect target and mechanism. The concrete operation procedure of "bone-approaching" method is recorded originally in Huangdi Neijing (Inner Canon of Yellow Emperor) as short needling and Shu needling (referring to the category of the five needling technique). The periosteum is the most effective stimulation target of "bone-approaching" acupuncture for analgesia, regaining consciousness and regulating spirit. The "bone-approaching" acupuncture is not only prominently effective on bone bi syndrome, but also has the unique effect on painful, encephalogenic and emotional diseases. The paper summarizes and improves "bone-approaching" acupuncture, i.e. "touching bone surface" with needle tip by slow insertion, "touching bone surface" without pain by swift insertion and "touching bone" with needle body by oblique insertion. It contributes to the inheritance, development and supplementation to the bone needling techniques in Huangdi Neijing and is significant for broadening the clinical application range of acupuncture.
Humans
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Acupuncture Therapy
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Periosteum
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Analgesia
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Pain Management
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Consciousness
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Pain
10. Effect of menthol, a transient receptor potential melastatin-8 channel activator, on pulmonary arterial hypertensive rats
Hao-Heng GTU ; Zhuang LI ; Jian-Qin YANG ; Wen-Bin FENG ; Xiao-Qing LIU ; Zi-Jian ZHAO ; Yun-Ping MU ; Fang-Hong LI ; Bin LI
Chinese Pharmacological Bulletin 2023;39(4):700-706
Aim To investigate the effects of menthol, a transient receptor potential melastatin-8 channel activator, on treating pulmonary arterial hypertension (PAH) in PAH model rats caused by monocrotaline (MCT). Methods Male Sprague-Dawley rats were divided into six groups randomly (control group, MCT group, MCT + menthol 1 mg • kg

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