The ethnic medicine for external use is an important dosage form in the external treatment methods of ethnic medicine.China has made significant progress in related research and applications.However,the regulations and guidelines for clinical research on external medicine are limited,and the related technologies and quality standards are not yet well-established in China.This article summarized the specific issues during the implementation of clinical research on ethnic medicine of external use:the research design failing to reflect the value and unique characteristics of these medicine;the big difficulty in the recruitment of participants,leading to delays in progress;inconsistent implementation of interventions;and the quality of research data needing to be improved,etc.Combining the authors'experience in project implementation management,this article proposed solutions to improve research quality and progress,including incorporating experts from various fields including ethnic medicine and research centers;refining participant recruitment strategies;analyzing factors affecting progress and optimizing the implementation process;and strengthening overall management and establishing a competitive enrollment mechanism.The article also shared a case study of the Tibetan medicine Qingpeng Ointment for the treatment of acute gouty arthritis,aiming to provide a reference for the clinical research on ethnic medicine of external use.

Chinese patent medicines for external use represent a distinct category of clinical drugs with unique therapeutic characteristics.At present,the research foundation of some topical Chinese patent medicines for external use is weak,and the accuracy and standardization of clinical application need to be improved.The research on clinical positioning of Chinese patent medicines for external use is of great significance for standardizing clinical medication,exploring the differentiated value of drugs and similar products,enhancing the safety of drug use,improving the efficiency of medical resource use,and promoting the secondary development and cultivation of drugs after listing.On the basis of summarizing the research status of clinical positioning of Chinese patent medicines for external use,this article put forward the significance,necessity and challenges of carrying out this research.Combined with the authors'practical experience,the authors put forward five experiences to carry out the post marketing clinical positioning research of Chinese patent medicines for external use,including distinguishing the theory of external treatment of Chinese materia medica,paying attention to the unmet needs in the modern medical system,not separating from the actual efficacy and dosage form characteristics of Chinese patent medicines for external use,clarifying the mechanism of"same treatment for different diseases",and verifying the clinical positioning hypothesis,which can provide references for relevant research.

To review the clinical characteristics, short-term outcomes, and risk factors of patients with infective endocarditis(IE) who underwent surgical treatment at a single center, and to summarize treatment experience.

The ethnic medicine for external use is an important dosage form in the external treatment methods of ethnic medicine.China has made significant progress in related research and applications.However,the regulations and guidelines for clinical research on external medicine are limited,and the related technologies and quality standards are not yet well-established in China.This article summarized the specific issues during the implementation of clinical research on ethnic medicine of external use:the research design failing to reflect the value and unique characteristics of these medicine;the big difficulty in the recruitment of participants,leading to delays in progress;inconsistent implementation of interventions;and the quality of research data needing to be improved,etc.Combining the authors'experience in project implementation management,this article proposed solutions to improve research quality and progress,including incorporating experts from various fields including ethnic medicine and research centers;refining participant recruitment strategies;analyzing factors affecting progress and optimizing the implementation process;and strengthening overall management and establishing a competitive enrollment mechanism.The article also shared a case study of the Tibetan medicine Qingpeng Ointment for the treatment of acute gouty arthritis,aiming to provide a reference for the clinical research on ethnic medicine of external use.

Chinese patent medicines for external use represent a distinct category of clinical drugs with unique therapeutic characteristics.At present,the research foundation of some topical Chinese patent medicines for external use is weak,and the accuracy and standardization of clinical application need to be improved.The research on clinical positioning of Chinese patent medicines for external use is of great significance for standardizing clinical medication,exploring the differentiated value of drugs and similar products,enhancing the safety of drug use,improving the efficiency of medical resource use,and promoting the secondary development and cultivation of drugs after listing.On the basis of summarizing the research status of clinical positioning of Chinese patent medicines for external use,this article put forward the significance,necessity and challenges of carrying out this research.Combined with the authors'practical experience,the authors put forward five experiences to carry out the post marketing clinical positioning research of Chinese patent medicines for external use,including distinguishing the theory of external treatment of Chinese materia medica,paying attention to the unmet needs in the modern medical system,not separating from the actual efficacy and dosage form characteristics of Chinese patent medicines for external use,clarifying the mechanism of"same treatment for different diseases",and verifying the clinical positioning hypothesis,which can provide references for relevant research.

Objective:Given the rising popularity of antibody-drug conjugate(ADC),this study was performed to assess the expression of hu-man epidermal growth factor receptor 2(HER-2)in metastatic colorectal cancer(mCRC)based on the Hofmann and HERACLES standards and to investigate its clinical significance.Methods:We evaluated 105 metastatic lesions and corresponding primary tumor tissues from 70 patients diagnosed with mCRC at Tianjin Medical University Cancer Institute&Hospital from January 2011 to December 2013.We assigned each patient to one of the three HER-2 expression classifications(HER-2 absent,HER-2 low,and HER-2 positive)separately using Hofmann and HERACLES criteria.We compared the consistency of the two evaluation criteria and the results between matched metastatic lesions and primary tumors.We also analyzed the correlation between HER-2 expression and clinicopathological factors in the patients.Results:HER-2 positivity rates based on Hofmann and HERACLES criteria were 3.8%(4/105)for metastatic lesions of mCRC and 7.1%(5/70)and 5.7%(4/70)for primary tumors,respectively.The detection rates of low HER-2 expression in both primary and metastatic lesions were higher with the Hofmann criteria(28.6%vs.25.7%)than with the HERACLES criteria(20.0%vs.11.4%).The consistency of HER-2 expression assess-ment between the two criteria was good(kappa coefficient:0.828).An inconsistency was observed in HER-2 expression between primary tu-mors and metastatic lesions(inconsistency rate,28.6%).Conclusions:The incidences of HER-2 positivity and low HER-2 expression were in-consistent between metastatic and primary lesions in mCRC,suggesting that clinical testing for both should be conducted simultaneously to improve the detection rates.The Hofmann criteria showed a higher detection rate for low HER-2 expression than that by the HERACLES cri-teria.Given the lack of a unified interpretation standard for HER-2 expression in CRC,the relationship between the clinical efficacy of ADC and HER-2 expression under different interpretation standards needs to be further evaluated in large-sample,multicenter studies.

The aim of this study was to prepare a high drug-carrying capacity micellar drug delivery system(CTD@Sol)of the polymer zebra tetracycline and to preliminarily investigate the feasibility of this drug delivery system for the treatment of breast cancer.Firstly,CTD@Sol was prepared using sol as the carrier material and CTD as the model drug,and its pharmacological properties such as appearance and morphology,particle size,potential and in vitro release were evaluated.The growth inhibitory and apoptotic effects of CTD@Sol on breast cancer(4T1)cells were investigated by MTT assay and Annexin V-FITC/PI double staining assay;the uptake efficiency of 4T1 to this delivery system was investigated by flow cytometry;and the in vivo tissue distribution of the delivery system and the targeting of tumour tissues were investigated by small animal in vivo imaging technique.The results showed that CTD@Sol appeared as a light pale blue creamy white colour,with an average particle size of(159.73±1.96)nm,a PDI of 0.198±0.006,Zeta potential of-(47.60±1.77)mV,an encapsulation rate of(90.29±1.69)%and a drug loading capacity of(45.00±0.84)%;the in vitro release and haemolysis experiments showed that the drug release rate of CTD@Sol in acidic environment(pH 5.5)was significantly faster than that in neutral environment(pH 7.4),suggesting that the system is acid-sensitive and has good biosafety under endocytosed pH conditions.Cellular uptake,cytotoxicity and apoptosis experiments showed that CTD@Sol was more lethal to 4T1 cells,and the sol-gel polymer micelles as a drug delivery vehicle could significantly improve the cellular uptake efficiency of the drug;in vivo experiments showed that the delivery system had a significant targeting effect on tumour tissues.In conclusion,this study has successfully produced a CTD@Sol drug delivery system with high drug loading capacity(>45%),good pharmacological performance,strong targeting and biosafety,which has the potential to be used in the treatment of breast cancer.

A 67-year-old male patient with primary liver cancer was given combination treatment with regorafenib and sintilimab because of disease progression after multiple interventional therapy. After one cycle of medication, the patient developed weakness in the left facial expression muscle and left upper eyelid, and generalized muscle pain with dyspnea. Laboratory tests showed myoglobin 8 614 μg/L, creatine kinase (CK) 17 480 U/L, CK-MB mass 528 μg/L, troponin I 0.465 μg/L, aspartate aminotransferase (AST) 1 069 U/L, alanine aminotransferase (ALT) 493 U/L, and lactate dehydrogenase (LDH) 2 469 U/L. The electrocardiogram showed the new onset of left bundle branch block. It was considered to be immune-related myositis, immune-related myalgia, and immune-related hepatitis caused by sintilimab, not excluding immune-related cardiac toxicity. Regorafenib and sintilimab were discontinued immediately while methylprednisolone pulse therapy was initiated at a dose of 500 mg (gradually reduced after 5 days), monoammonium glycyrrhizinate and cysteine and sodium chloride injection and bicyclol were administered for liver protection and reducing liver enzyme levels. After 7 days of treatments, weakness in the left facial expression muscle and eyelid were improved significantly along with relief from chest tightness and alleviation of generalized muscle pain throughout the body. After 15 days of treatments, laboratory tests showed myoglobin 494 μg/L, CK 537 U/L, CK-MB mass 115 μg/L, AST 52 U/L, ALT 77 U/L, and LDH 519 U/L. After half a year of treatments, glucocorticoids therapy was discontinued, and all indicators returned basically to normal. The patient did not receive immunotherapy again.

Objective:Given the rising popularity of antibody-drug conjugate(ADC),this study was performed to assess the expression of hu-man epidermal growth factor receptor 2(HER-2)in metastatic colorectal cancer(mCRC)based on the Hofmann and HERACLES standards and to investigate its clinical significance.Methods:We evaluated 105 metastatic lesions and corresponding primary tumor tissues from 70 patients diagnosed with mCRC at Tianjin Medical University Cancer Institute&Hospital from January 2011 to December 2013.We assigned each patient to one of the three HER-2 expression classifications(HER-2 absent,HER-2 low,and HER-2 positive)separately using Hofmann and HERACLES criteria.We compared the consistency of the two evaluation criteria and the results between matched metastatic lesions and primary tumors.We also analyzed the correlation between HER-2 expression and clinicopathological factors in the patients.Results:HER-2 positivity rates based on Hofmann and HERACLES criteria were 3.8%(4/105)for metastatic lesions of mCRC and 7.1%(5/70)and 5.7%(4/70)for primary tumors,respectively.The detection rates of low HER-2 expression in both primary and metastatic lesions were higher with the Hofmann criteria(28.6%vs.25.7%)than with the HERACLES criteria(20.0%vs.11.4%).The consistency of HER-2 expression assess-ment between the two criteria was good(kappa coefficient:0.828).An inconsistency was observed in HER-2 expression between primary tu-mors and metastatic lesions(inconsistency rate,28.6%).Conclusions:The incidences of HER-2 positivity and low HER-2 expression were in-consistent between metastatic and primary lesions in mCRC,suggesting that clinical testing for both should be conducted simultaneously to improve the detection rates.The Hofmann criteria showed a higher detection rate for low HER-2 expression than that by the HERACLES cri-teria.Given the lack of a unified interpretation standard for HER-2 expression in CRC,the relationship between the clinical efficacy of ADC and HER-2 expression under different interpretation standards needs to be further evaluated in large-sample,multicenter studies.

A 67-year-old male patient with primary liver cancer was given combination treatment with regorafenib and sintilimab because of disease progression after multiple interventional therapy. After one cycle of medication, the patient developed weakness in the left facial expression muscle and left upper eyelid, and generalized muscle pain with dyspnea. Laboratory tests showed myoglobin 8 614 μg/L, creatine kinase (CK) 17 480 U/L, CK-MB mass 528 μg/L, troponin I 0.465 μg/L, aspartate aminotransferase (AST) 1 069 U/L, alanine aminotransferase (ALT) 493 U/L, and lactate dehydrogenase (LDH) 2 469 U/L. The electrocardiogram showed the new onset of left bundle branch block. It was considered to be immune-related myositis, immune-related myalgia, and immune-related hepatitis caused by sintilimab, not excluding immune-related cardiac toxicity. Regorafenib and sintilimab were discontinued immediately while methylprednisolone pulse therapy was initiated at a dose of 500 mg (gradually reduced after 5 days), monoammonium glycyrrhizinate and cysteine and sodium chloride injection and bicyclol were administered for liver protection and reducing liver enzyme levels. After 7 days of treatments, weakness in the left facial expression muscle and eyelid were improved significantly along with relief from chest tightness and alleviation of generalized muscle pain throughout the body. After 15 days of treatments, laboratory tests showed myoglobin 494 μg/L, CK 537 U/L, CK-MB mass 115 μg/L, AST 52 U/L, ALT 77 U/L, and LDH 519 U/L. After half a year of treatments, glucocorticoids therapy was discontinued, and all indicators returned basically to normal. The patient did not receive immunotherapy again.