Objective:To analyze the antifungal effects of Chinese herb monomers,i.e.berberine,baicalin,eugenol and curcumin,on Candida albicans.Methods:After Candida albicans strain Y01-09 was incubated for 48 h in YEPD broth wh...Objective:To analyze the antifungal effects of Chinese herb monomers,i.e.berberine,baicalin,eugenol and curcumin,on Candida albicans.Methods:After Candida albicans strain Y01-09 was incubated for 48 h in YEPD broth which contained different concentrations of Chinese herb components,the cell cycle,fluorescent intensity and the size of cell volume were detected by flow cytometry.Results:The 4 Chinese herb monomers could affect the cell cycle of Candida albicans in different ranges.The ratio of cells in S-G2-M period decreased as the agents concentration increased,indicating that the cell division was inhibited.The fluorescent intensity of Candida albicans cells became weaker after being incubated,which reflected the loss of DNA fragments.The higher the concentration was,the weaker the fluorescent intensity became.The cell size,cell diopter and particle size changed much as the agents concentration increased.Conclusion:Chinese herb monomers play the antifungal role in inhibiting cell division.FCM could be used to determine the susceptibility of antifungal agents.展开更多
Objective: To investigate the effects of baicalin on expression of inducible nitric oxide syn-thase (iNOS) in fibroblasts and its mechanisms in treating psoriasis. Methods: Fibroblasts cultured in vitro were stimulate...Objective: To investigate the effects of baicalin on expression of inducible nitric oxide syn-thase (iNOS) in fibroblasts and its mechanisms in treating psoriasis. Methods: Fibroblasts cultured in vitro were stimulated with tumor necrosis factor-α (TNF-α), interferon-γ(IFN-γ), interleukin-8 (IL-8) in different groups. iNOS was detected by western blot and immunocytochemistry assay, and in addition, the effects of baicalin on its expression were investigated. Results: Fibroblasts did not express iNOS without cytokine stimulation. When treated for 24 h with 1.0×106 U/LTNF-α, 0.2×106U/L IFN-γ, 0.2×106 pg/L IL-8 alone or in combinations indicated, fibroblasts produced iNOS when stimulated by TNF-α alone while neither IFN-γ nor IL-8 could induce the production of iNOS. The combination of TNF-α and IL-8 induced a strong expression of iNOS, the combined exposure of three kinds of cytokines showed an even stronger effects. The strongly stained area was in the cytoplasm near the nuclei. Expression of iNOS induced by TNF-α and IL-8 was inhibited by 50μg/ ml of baicalin. Conclusion: Fibroblasts might express iNOS when stimulated by certain cytokines. Baicalin decreased production of nitric oxide through inhibiting the expression of iNOS, furthermore it reduced inflammation, which might be part of its mechanisms in treating psoriasis.展开更多
THE FIRST CASE of AIDS in the USA was recognized two decades ago,with the early cases representing homosexuals with pneumocystic carinii pneumonia or Kaposi’s sarcoma.Since then the disease has spread world wide with...THE FIRST CASE of AIDS in the USA was recognized two decades ago,with the early cases representing homosexuals with pneumocystic carinii pneumonia or Kaposi’s sarcoma.Since then the disease has spread world wide without sparing any continent.HIV has caused deaths and severe socio-economic impact in developed and under developing countries.展开更多
Objective: To explore the regulatory mechanism of Xiaoyin Recipe (消银方) on the T helper 1/ T helper 2 (Th1/Th2) immune balance. Methods: Thirty-six experimental animals were divided into three groups, 12 rats ...Objective: To explore the regulatory mechanism of Xiaoyin Recipe (消银方) on the T helper 1/ T helper 2 (Th1/Th2) immune balance. Methods: Thirty-six experimental animals were divided into three groups, 12 rats in each group: blank control group (B group), negative control group (N group), and Xiaoyin Recipe treatment group (T group). The latter two groups received immunization of experimental autoimmune thyroiditis (EAT), and T group were treated with Xiaoyin Recipe for a month. Then, the expression of Th1-Th2-related genes in peripheral blood mononuclear cells (PBMCs) were screened with Oligo GEArray Rat Thl-Th2-Th3 Microarray. The expressions of tumor necrosis factor- α (TNF- α), interleukin-10 (IL-10), T-box expressed in T-cells (T-bet), and GATA-binding protein-3 (GATA-3) were detected by real-time polymerase chain reaction (RT-PCR). Results: Gene array screening showed that compared to N group, in T group after Xiaoyin Recipe treatment, 3 genes were upregulated in EAT rats, including interleukin-27 receptor alpha (IL-27roL), glomulin (GImn), and GATA-3, while 38 genes were downregulated, such as CD28, IL-18, signal transducer, and activator of transcription 1 (STAT1), T-bet, TNF receptor superfamily member 4 (TNFRSF4), TNF ligand superfamily member 5 (TNFSF5), and TNF receptor superfamily member 5 (TNFRSF5). While RT-PCR showed that there was an increased level of TNF-α mRNA (P〈0.01), an elevated ratio of T-bet/GATA-3, and a decreased level of IL-10 mRNA in PBMC of N and T group compared to B group (P〈0.01); and after treatment with Xiaoyin Recipe, IL-10 mRNA level increased (P〈0.01), while TNF-α mRNA level and T-bet/GATA-3 ratio decreased in T group compared to N group (P〈0.01). Conclusion: Xiaoyin Recipe for psoriasis could induce a Thl/Th2 balance drift toward Th2 in PBMC of EAT rats and thus improve the conditions.展开更多
Psoriasis is a common, chronic, recurrent inflammatory skin disorder whose etiology is still unknown. It is believed that a multiple-gene inheritance is involved and it also involves various factors such as immunity, ...Psoriasis is a common, chronic, recurrent inflammatory skin disorder whose etiology is still unknown. It is believed that a multiple-gene inheritance is involved and it also involves various factors such as immunity, inflammation, cell proliferation, apoptosis, neural media, etc. Since cytokines are key mediators in inflammation, a number of Chinese medicines (CMs) have been reported to have certain antagonist effects on pro-inflammatory cytokines such as tumor necrosis factor-α (TNF-α), platelet active factor (PAF) and interleukin-8 (IL-8). Some researches on CMs have made significant breakthroughs in psoriasis by intervening with cytokines. Abnormalities with keratinocyte proliferation and apoptosis are considered to be present in patients with psoriasis and a number of studies show that the mechanism of CMs on psoriasis may be through the inhibition of the keratinocyte proliferation and induction of apoptosis. Other studies also show that the inhibition of fibroblast-secreted cytokines could regulate keratinocyte proliferation and differentiation and reduce the level of Calcitonin gene-related peptide (CGRP) in plasma and in lesions so as to slow down the process of inflammation and proliferation in psoriasis. The most commonly used models for psoriasis are the scaled tails or the vaginal epithelium of mice in China. They were used to observe the histopathological changes after the model mice were treated with CMs with the inhibition on the mitosis of vaginal epithelium or promotion of granular layer in rat tail taken as the indices of clinical efficacy. A variety of signs occur in psoriasis patients with TCM blood-stasis syndrome type and the effect of CMs in activating blood circulation to remove blood stasis on psoriasis suggested that the mechanism of CMs may be partially correlated to hemorrheology and microcirculation. Along with the continuous development of the biosciences, some TCM theories for psoriasis have been confirmed by laboratory studies. However, the exploration into traditional Chinese medicines' biomechanics in psoriasis and the therapeutic mechanism of CMs by integrative medicine still requires further studies.展开更多
Background:Reports on the prevalence of psoriatic arthritis(PsA)among Chinese patients with psoriasis are very limited.This study,conducted by rheumatologists,estimated the prevalence of PsA in a large number of Chine...Background:Reports on the prevalence of psoriatic arthritis(PsA)among Chinese patients with psoriasis are very limited.This study,conducted by rheumatologists,estimated the prevalence of PsA in a large number of Chinese patients with psoriasis.Methods:Consecutive patients with a confirmed diagnosis of psoriasis attending nine dermatology clinics in five hospitals were recruited.All psoriasis patients were asked to complete a questionnaire comprising 16 questions to identify possible cases of PsA.All patients with one or more positive answers to the questionnaire were evaluated by two experienced rheumatologists.Results:A total of 2434 psoriasis patients,including 1561 males and 873 females,were enrolled.Both the questionnaire and rheumatologists’examinations were completed in the dermatology clinics.The results identified 252 patients with PsA,comprising 168 males and 84 females.The overall prevalence of PsA among psoriasis patients was 10.4%(95%confidence interval[95%CI],9.1%-11.7%).By sex,the prevalence was 10.8%(95%CI,9.2%-12.5%)for males and 9.6%(95%CI,7.7%-11.9%)for females and there was no significant sex difference in the prevalence of PsA(P=0.38).Of the 252 PsA patients,125(49.6%,95%CI,41.3%-59.1%)were newly diagnosed by rheumatologists.Consequently,the prevalence of undiagnosed PsA among psoriasis patients was 5.2%(95%CI,4.4%-6.2%).Conclusion:The prevalence of PsA in the Chinese population with psoriasis is about 10.4%,which is almost double that of previous reports in the Chinese population,but lower than that in Caucasians.展开更多
Background:Psoriasis is a chronic inflammatory skin disease,affecting about 0.6%of the Chinese population.Many patients are not well controlled by conventional treatments,thus there is need for new treatment regimens....Background:Psoriasis is a chronic inflammatory skin disease,affecting about 0.6%of the Chinese population.Many patients are not well controlled by conventional treatments,thus there is need for new treatment regimens.In this study,we assessed the efficacy and safety of secukinumab in Chinese patients with moderate to severe plaque psoriasis.Methods:This study was a 52-week,multicentre,randomized,double-blind,placebo-controlled,parallel-group,Phase 3 trial.A sub-population of study participants(≥18 years)of Chinese ethnicity were randomized to receive subcutaneous injections of 300 or 150 mg secukinumab,or placebo.The co-primary endpoints were psoriasis area severity index(PASI)75 and Investigator’s Global Assessment(IGA)0/1 at Week 12.Results:A total of 441 Chinese patients were enrolled in this study.Co-primary outcomes were achieved;300 and 150 mg secukinumab were superior to placebo as shown in the proportion of patients that achieved PASI 75(97.7%and 87.2%vs.3.7%,respectively;P<0.001),and IGA 0/1(82.3%and 69.7%vs.2.7%;P<0.001)at Week 12.Treatment efficacy was maintained until Week 52.There was no increase in overall adverse events with secukinumab relative to placebo throughout the 52-week period.Conclusion:Secukinumab is highly effective and well tolerated in Chinese patients with moderate to severe plaque psoriasis.展开更多
Objective:To study the effects of low concentration of ar senic (As 2O 3) on DNA synthesis and related transcription factor gene E2F1 express ion in keratinocyte. Methods:Human epidermal keratinocyte (cell line HaCa...Objective:To study the effects of low concentration of ar senic (As 2O 3) on DNA synthesis and related transcription factor gene E2F1 express ion in keratinocyte. Methods:Human epidermal keratinocyte (cell line HaCaT) cultured in vitro was used. After treatment with various concentrations of arsenic, DNA s ynthesis and E2F1 expression in HaCaT cells were detected by using 3H-TdR method and RT-PCR.Results:Arsenic caused a modest increase of keratinocyte DNA synth esis when the concentration reached the range within 0.5-16 nmol/L, but the amo unt of incorporated 3H-TdR decreased and returned to baseline level when th e concentration of arsenic increased to over 16 nmol/L. RT-PCR analysis showe d the level of E2F1 mRNA was elevated in HaCaT cells with the increase of DNA sy nthesis. Conclusion:Arsenic of a certain concentration could increase DNA s ynthesis and enhance E2F1 expression in HaCaT cell line, which might be one of t he pathological mechanisms of skin disease related to arsenic.展开更多
We reported an unusual case of disseminated cryptococcal lymphadenitis in an immunocompetent host who presented with fever and lymphadenopathy, which were the only two symptoms and signs. Latex agglutination test of s...We reported an unusual case of disseminated cryptococcal lymphadenitis in an immunocompetent host who presented with fever and lymphadenopathy, which were the only two symptoms and signs. Latex agglutination test of serum and cerebrospinal fluid (CSF) were negative, while lymph node biopsy showed Cryptococcus neoformans. A diagnosis of disseminated cryptococcal lymphadenitis was made. Then the patient was treated with amphotericin B for 15 days as initial therapy and itraconazole for 6 months as maintenance therapy respectively. The patient received re-examination per 6 months and was followed up for 2 years. Swollen lymph nodes diminished gradually, and no fever or other symptoms were found. Latex agglutination test of serum and CSF were negative throughout the follow-up period, and anti-HIV, syphilis and tuberculosis antibody were all negative.展开更多
Biologic drugs have been increasingly used in the treatment of psoriasis and are especially favorable for severe,recalcitrant,and special-type cases.Therefore,appropriate,effective,and safe use of biologic drugs has d...Biologic drugs have been increasingly used in the treatment of psoriasis and are especially favorable for severe,recalcitrant,and special-type cases.Therefore,appropriate,effective,and safe use of biologic drugs has drawn attention from dermatologists.For this purpose,Chinese experts majoring in psoriasis analyzed domestic and international research data,summarized current clinical experiences,investigated features of Chinese patients with psoriasis,and finally formulated the present consensus,which provides detailed guidances to clinicians in terms of the principles and methods of the application of biologics,the efficacy and safety profile,patient screening and monitoring,main adverse events and corresponding solutions,and precautions for special patient populations.展开更多
文摘Objective:To analyze the antifungal effects of Chinese herb monomers,i.e.berberine,baicalin,eugenol and curcumin,on Candida albicans.Methods:After Candida albicans strain Y01-09 was incubated for 48 h in YEPD broth which contained different concentrations of Chinese herb components,the cell cycle,fluorescent intensity and the size of cell volume were detected by flow cytometry.Results:The 4 Chinese herb monomers could affect the cell cycle of Candida albicans in different ranges.The ratio of cells in S-G2-M period decreased as the agents concentration increased,indicating that the cell division was inhibited.The fluorescent intensity of Candida albicans cells became weaker after being incubated,which reflected the loss of DNA fragments.The higher the concentration was,the weaker the fluorescent intensity became.The cell size,cell diopter and particle size changed much as the agents concentration increased.Conclusion:Chinese herb monomers play the antifungal role in inhibiting cell division.FCM could be used to determine the susceptibility of antifungal agents.
基金This Project is supported by State Natural Science Foun-dation(No.30271197)
文摘Objective: To investigate the effects of baicalin on expression of inducible nitric oxide syn-thase (iNOS) in fibroblasts and its mechanisms in treating psoriasis. Methods: Fibroblasts cultured in vitro were stimulated with tumor necrosis factor-α (TNF-α), interferon-γ(IFN-γ), interleukin-8 (IL-8) in different groups. iNOS was detected by western blot and immunocytochemistry assay, and in addition, the effects of baicalin on its expression were investigated. Results: Fibroblasts did not express iNOS without cytokine stimulation. When treated for 24 h with 1.0×106 U/LTNF-α, 0.2×106U/L IFN-γ, 0.2×106 pg/L IL-8 alone or in combinations indicated, fibroblasts produced iNOS when stimulated by TNF-α alone while neither IFN-γ nor IL-8 could induce the production of iNOS. The combination of TNF-α and IL-8 induced a strong expression of iNOS, the combined exposure of three kinds of cytokines showed an even stronger effects. The strongly stained area was in the cytoplasm near the nuclei. Expression of iNOS induced by TNF-α and IL-8 was inhibited by 50μg/ ml of baicalin. Conclusion: Fibroblasts might express iNOS when stimulated by certain cytokines. Baicalin decreased production of nitric oxide through inhibiting the expression of iNOS, furthermore it reduced inflammation, which might be part of its mechanisms in treating psoriasis.
文摘THE FIRST CASE of AIDS in the USA was recognized two decades ago,with the early cases representing homosexuals with pneumocystic carinii pneumonia or Kaposi’s sarcoma.Since then the disease has spread world wide without sparing any continent.HIV has caused deaths and severe socio-economic impact in developed and under developing countries.
文摘Objective: To explore the regulatory mechanism of Xiaoyin Recipe (消银方) on the T helper 1/ T helper 2 (Th1/Th2) immune balance. Methods: Thirty-six experimental animals were divided into three groups, 12 rats in each group: blank control group (B group), negative control group (N group), and Xiaoyin Recipe treatment group (T group). The latter two groups received immunization of experimental autoimmune thyroiditis (EAT), and T group were treated with Xiaoyin Recipe for a month. Then, the expression of Th1-Th2-related genes in peripheral blood mononuclear cells (PBMCs) were screened with Oligo GEArray Rat Thl-Th2-Th3 Microarray. The expressions of tumor necrosis factor- α (TNF- α), interleukin-10 (IL-10), T-box expressed in T-cells (T-bet), and GATA-binding protein-3 (GATA-3) were detected by real-time polymerase chain reaction (RT-PCR). Results: Gene array screening showed that compared to N group, in T group after Xiaoyin Recipe treatment, 3 genes were upregulated in EAT rats, including interleukin-27 receptor alpha (IL-27roL), glomulin (GImn), and GATA-3, while 38 genes were downregulated, such as CD28, IL-18, signal transducer, and activator of transcription 1 (STAT1), T-bet, TNF receptor superfamily member 4 (TNFRSF4), TNF ligand superfamily member 5 (TNFSF5), and TNF receptor superfamily member 5 (TNFRSF5). While RT-PCR showed that there was an increased level of TNF-α mRNA (P〈0.01), an elevated ratio of T-bet/GATA-3, and a decreased level of IL-10 mRNA in PBMC of N and T group compared to B group (P〈0.01); and after treatment with Xiaoyin Recipe, IL-10 mRNA level increased (P〈0.01), while TNF-α mRNA level and T-bet/GATA-3 ratio decreased in T group compared to N group (P〈0.01). Conclusion: Xiaoyin Recipe for psoriasis could induce a Thl/Th2 balance drift toward Th2 in PBMC of EAT rats and thus improve the conditions.
文摘Psoriasis is a common, chronic, recurrent inflammatory skin disorder whose etiology is still unknown. It is believed that a multiple-gene inheritance is involved and it also involves various factors such as immunity, inflammation, cell proliferation, apoptosis, neural media, etc. Since cytokines are key mediators in inflammation, a number of Chinese medicines (CMs) have been reported to have certain antagonist effects on pro-inflammatory cytokines such as tumor necrosis factor-α (TNF-α), platelet active factor (PAF) and interleukin-8 (IL-8). Some researches on CMs have made significant breakthroughs in psoriasis by intervening with cytokines. Abnormalities with keratinocyte proliferation and apoptosis are considered to be present in patients with psoriasis and a number of studies show that the mechanism of CMs on psoriasis may be through the inhibition of the keratinocyte proliferation and induction of apoptosis. Other studies also show that the inhibition of fibroblast-secreted cytokines could regulate keratinocyte proliferation and differentiation and reduce the level of Calcitonin gene-related peptide (CGRP) in plasma and in lesions so as to slow down the process of inflammation and proliferation in psoriasis. The most commonly used models for psoriasis are the scaled tails or the vaginal epithelium of mice in China. They were used to observe the histopathological changes after the model mice were treated with CMs with the inhibition on the mitosis of vaginal epithelium or promotion of granular layer in rat tail taken as the indices of clinical efficacy. A variety of signs occur in psoriasis patients with TCM blood-stasis syndrome type and the effect of CMs in activating blood circulation to remove blood stasis on psoriasis suggested that the mechanism of CMs may be partially correlated to hemorrheology and microcirculation. Along with the continuous development of the biosciences, some TCM theories for psoriasis have been confirmed by laboratory studies. However, the exploration into traditional Chinese medicines' biomechanics in psoriasis and the therapeutic mechanism of CMs by integrative medicine still requires further studies.
基金National Natural Science Foundation of China(No.82271837)
文摘Background:Reports on the prevalence of psoriatic arthritis(PsA)among Chinese patients with psoriasis are very limited.This study,conducted by rheumatologists,estimated the prevalence of PsA in a large number of Chinese patients with psoriasis.Methods:Consecutive patients with a confirmed diagnosis of psoriasis attending nine dermatology clinics in five hospitals were recruited.All psoriasis patients were asked to complete a questionnaire comprising 16 questions to identify possible cases of PsA.All patients with one or more positive answers to the questionnaire were evaluated by two experienced rheumatologists.Results:A total of 2434 psoriasis patients,including 1561 males and 873 females,were enrolled.Both the questionnaire and rheumatologists’examinations were completed in the dermatology clinics.The results identified 252 patients with PsA,comprising 168 males and 84 females.The overall prevalence of PsA among psoriasis patients was 10.4%(95%confidence interval[95%CI],9.1%-11.7%).By sex,the prevalence was 10.8%(95%CI,9.2%-12.5%)for males and 9.6%(95%CI,7.7%-11.9%)for females and there was no significant sex difference in the prevalence of PsA(P=0.38).Of the 252 PsA patients,125(49.6%,95%CI,41.3%-59.1%)were newly diagnosed by rheumatologists.Consequently,the prevalence of undiagnosed PsA among psoriasis patients was 5.2%(95%CI,4.4%-6.2%).Conclusion:The prevalence of PsA in the Chinese population with psoriasis is about 10.4%,which is almost double that of previous reports in the Chinese population,but lower than that in Caucasians.
基金This study was sponsored by Novartis Pharma AG,Basel,Switzerland。
文摘Background:Psoriasis is a chronic inflammatory skin disease,affecting about 0.6%of the Chinese population.Many patients are not well controlled by conventional treatments,thus there is need for new treatment regimens.In this study,we assessed the efficacy and safety of secukinumab in Chinese patients with moderate to severe plaque psoriasis.Methods:This study was a 52-week,multicentre,randomized,double-blind,placebo-controlled,parallel-group,Phase 3 trial.A sub-population of study participants(≥18 years)of Chinese ethnicity were randomized to receive subcutaneous injections of 300 or 150 mg secukinumab,or placebo.The co-primary endpoints were psoriasis area severity index(PASI)75 and Investigator’s Global Assessment(IGA)0/1 at Week 12.Results:A total of 441 Chinese patients were enrolled in this study.Co-primary outcomes were achieved;300 and 150 mg secukinumab were superior to placebo as shown in the proportion of patients that achieved PASI 75(97.7%and 87.2%vs.3.7%,respectively;P<0.001),and IGA 0/1(82.3%and 69.7%vs.2.7%;P<0.001)at Week 12.Treatment efficacy was maintained until Week 52.There was no increase in overall adverse events with secukinumab relative to placebo throughout the 52-week period.Conclusion:Secukinumab is highly effective and well tolerated in Chinese patients with moderate to severe plaque psoriasis.
文摘Objective:To study the effects of low concentration of ar senic (As 2O 3) on DNA synthesis and related transcription factor gene E2F1 express ion in keratinocyte. Methods:Human epidermal keratinocyte (cell line HaCaT) cultured in vitro was used. After treatment with various concentrations of arsenic, DNA s ynthesis and E2F1 expression in HaCaT cells were detected by using 3H-TdR method and RT-PCR.Results:Arsenic caused a modest increase of keratinocyte DNA synth esis when the concentration reached the range within 0.5-16 nmol/L, but the amo unt of incorporated 3H-TdR decreased and returned to baseline level when th e concentration of arsenic increased to over 16 nmol/L. RT-PCR analysis showe d the level of E2F1 mRNA was elevated in HaCaT cells with the increase of DNA sy nthesis. Conclusion:Arsenic of a certain concentration could increase DNA s ynthesis and enhance E2F1 expression in HaCaT cell line, which might be one of t he pathological mechanisms of skin disease related to arsenic.
文摘We reported an unusual case of disseminated cryptococcal lymphadenitis in an immunocompetent host who presented with fever and lymphadenopathy, which were the only two symptoms and signs. Latex agglutination test of serum and cerebrospinal fluid (CSF) were negative, while lymph node biopsy showed Cryptococcus neoformans. A diagnosis of disseminated cryptococcal lymphadenitis was made. Then the patient was treated with amphotericin B for 15 days as initial therapy and itraconazole for 6 months as maintenance therapy respectively. The patient received re-examination per 6 months and was followed up for 2 years. Swollen lymph nodes diminished gradually, and no fever or other symptoms were found. Latex agglutination test of serum and CSF were negative throughout the follow-up period, and anti-HIV, syphilis and tuberculosis antibody were all negative.
文摘Biologic drugs have been increasingly used in the treatment of psoriasis and are especially favorable for severe,recalcitrant,and special-type cases.Therefore,appropriate,effective,and safe use of biologic drugs has drawn attention from dermatologists.For this purpose,Chinese experts majoring in psoriasis analyzed domestic and international research data,summarized current clinical experiences,investigated features of Chinese patients with psoriasis,and finally formulated the present consensus,which provides detailed guidances to clinicians in terms of the principles and methods of the application of biologics,the efficacy and safety profile,patient screening and monitoring,main adverse events and corresponding solutions,and precautions for special patient populations.