The literature on the characteristics, commodity grade specifications and chemical composition of Angelicae Sinensis Radix was reviewed. It was found that the main factors affecting the changes of traits and chemical composition of Angelicae Sinensis Radix included origin, altitude, climate, soil, cultivation methods, processing and processing methods and storage methods. Among them, the volatile oil types and ferulic acid content of Angelicae Sinensis Radix produced in Minxian County of Gansu Province were better than those in some non-authentic producing areas, but some component differences remained to be verified; direct seeding and film mulching cultivation could improve the yield, volatile oil and polysaccharide content of Angelicae Sinensis Radix; continuous cropping may lead to rhizosphere soil problems of Angelicae Sinensis Radix, and rotation or intercropping could be considered; drying in the shade and smoking drying could retain the oil and aroma of Angelicae Sinensis Radix; wine stir-frying method could increase the content of Z-ligustilide, but stir-frying carbon may reduce the content of ferulic acid; high temperature and high humidity storage may affect the content of ligustilide. In the future, the quality evaluation system of Angelicae Sinensis Radix should be strengthened and improved, genuine research should be strengthened, and scientific field management methods and appropriate harvesting and processing methods should be established, so as to ensure the good clinical efficacy and stable and controllable quality of Angelicae Sinensis Radix.

Objective Through reviewing the herbs,medical books and classic prescriptions of the past dynasties,the herbal examination of Gypsum fibrosum and its analogs was carried out to clarify the relationship between them.The qualitative analysis was carried out by single-point Raman,infrared,near infrared and XRD techniques,the quantitative analysis of the main components was carried out by EDTA titration and Raman surface scanning technique,the elemental analysis was carried out by ICP-OES,and the differences between gypsum and argillite were observed by scanning electron microscope.Results Gypsum fibrosum is mixed with marble,feldspar,north cold-water stone,south cold-water stone and xuanjing stone and so on.Before the Ming Dynasty,there was no differentiation between soft and anhydrite,and after the Ming Dynasty,it was clear that gypsum was soft gypsum and feldspar was anhydrite;in modern times,marble is also made to be gypsum for medicinal use;Feldspar is anhydrite and is no longer made to be used for medicinal use,north cold-water stone is red gypsum,and south cold-water stone is calcite.Gypsum,south coldwater stone is calcite.The peaks of argillite appeared to be buried in the Raman spectrum compared with Gypsum fibrosum,and the original profiles of both infrared and near-infrared were basically the same,and the near-infrared model established by the preprocessing method of the first-order derivatives plus vector normalization(5-point smoothing)could effectively differentiate between Gypsum fibrosum and its analogues,but it could not differentiate between argillite and Gypsum fibrosum with high content.XRD showed that there are differences in the relative intensities of the peaks of argillite and Gypsum fibrosum,and some XRD shows that there are differences in the relative intensities of the peaks of basalt and Gypsum fibrosum,and some of the peaks of basalt are characterized by impurities such as quartz,and the contents of trace elements such as Fe,Mn,Cr,Pb,Hg and As are higher in basalt.The peak shapes of XRD,Raman spectra,infrared spectra and near-infrared spectra of Gypsum fibrosum and calcined gypsum are closer but can still be distinguished,and the Ca content of calcined gypsum is higher than that of gypsum.Commercially available south chrysocolla and stalactite source are carbonate minerals calcite calcite.Spectral detection can not be distinguished,the trace element content is basically the same,but the traits are different.North chrysocolla(red gypsum)is higher than the Fe content of commercially available white gypsum.Raman surface scanning not only can be a qualitative and quantitative determination of minerals such as gypsum and other minerals,and the results of the content of the titration is basically similar,but also to determine the state of Gypsum fibrosum and calcined gypsum calcined water loss status and the degree of calcined gypsum.The results of Raman surface scanning are similar to the titration results.Conclusion This study can provide a scientific basis for the traceability of Gypsum fibrosum,and can better guide the clinical use of medicine and the rational use of resources.

Objective Through reviewing the herbs,medical books and classic prescriptions of the past dynasties,the herbal examination of Gypsum fibrosum and its analogs was carried out to clarify the relationship between them.The qualitative analysis was carried out by single-point Raman,infrared,near infrared and XRD techniques,the quantitative analysis of the main components was carried out by EDTA titration and Raman surface scanning technique,the elemental analysis was carried out by ICP-OES,and the differences between gypsum and argillite were observed by scanning electron microscope.Results Gypsum fibrosum is mixed with marble,feldspar,north cold-water stone,south cold-water stone and xuanjing stone and so on.Before the Ming Dynasty,there was no differentiation between soft and anhydrite,and after the Ming Dynasty,it was clear that gypsum was soft gypsum and feldspar was anhydrite;in modern times,marble is also made to be gypsum for medicinal use;Feldspar is anhydrite and is no longer made to be used for medicinal use,north cold-water stone is red gypsum,and south cold-water stone is calcite.Gypsum,south coldwater stone is calcite.The peaks of argillite appeared to be buried in the Raman spectrum compared with Gypsum fibrosum,and the original profiles of both infrared and near-infrared were basically the same,and the near-infrared model established by the preprocessing method of the first-order derivatives plus vector normalization(5-point smoothing)could effectively differentiate between Gypsum fibrosum and its analogues,but it could not differentiate between argillite and Gypsum fibrosum with high content.XRD showed that there are differences in the relative intensities of the peaks of argillite and Gypsum fibrosum,and some XRD shows that there are differences in the relative intensities of the peaks of basalt and Gypsum fibrosum,and some of the peaks of basalt are characterized by impurities such as quartz,and the contents of trace elements such as Fe,Mn,Cr,Pb,Hg and As are higher in basalt.The peak shapes of XRD,Raman spectra,infrared spectra and near-infrared spectra of Gypsum fibrosum and calcined gypsum are closer but can still be distinguished,and the Ca content of calcined gypsum is higher than that of gypsum.Commercially available south chrysocolla and stalactite source are carbonate minerals calcite calcite.Spectral detection can not be distinguished,the trace element content is basically the same,but the traits are different.North chrysocolla(red gypsum)is higher than the Fe content of commercially available white gypsum.Raman surface scanning not only can be a qualitative and quantitative determination of minerals such as gypsum and other minerals,and the results of the content of the titration is basically similar,but also to determine the state of Gypsum fibrosum and calcined gypsum calcined water loss status and the degree of calcined gypsum.The results of Raman surface scanning are similar to the titration results.Conclusion This study can provide a scientific basis for the traceability of Gypsum fibrosum,and can better guide the clinical use of medicine and the rational use of resources.

Rare diseases are a collective term for diseases with extremely low prevalence and incidence rates.Up to now,China has released two lists identifying a total of 207 rare diseases.Given that most rare diseases do not have drugs with corresponding indications,physicians frequently resort to using off-label drugs when treating patients with rare diseases.However,there is currently no systematic guideline or expert consensus for the use of off-label medications in China.To comprehensively collect existing evidence of off-label drug use for rare diseases,fully analyze and evaluate the rationality of off-label drug use for rare diseases,and standardize the management of off-label drug use for rare diseases,the Rare Disease Branch of Beijing Medical Association,Chinese Pharmaceutical Association,Beijing Pharmaceutical Association,and the School of Public Health,Peking University have jointly initiated the drafting of the Expert Consensus on Off-label Use of Drugs for Rare Diseases.This consensus refer to the WHO Handbook for Guideline Development,the Guidelines for Developing/Revising Clinical Diagnostic and Treatment Guidelines in China(2022 Edition),the AGREE Ⅱ and the STAR tools.This protocol outlines the background and purpose of consensus,as well as the comprehensive framework for consensus development,encompassing panel formation,clinical issue identification,evidence retrieval,data extraction,and evidence-based recommendation formulation.

Rare diseases are a collective term for diseases with extremely low prevalence and incidence rates.Up to now,China has released two lists identifying a total of 207 rare diseases.Given that most rare diseases do not have drugs with corresponding indications,physicians frequently resort to using off-label drugs when treating patients with rare diseases.However,there is currently no systematic guideline or expert consensus for the use of off-label medications in China.To comprehensively collect existing evidence of off-label drug use for rare diseases,fully analyze and evaluate the rationality of off-label drug use for rare diseases,and standardize the management of off-label drug use for rare diseases,the Rare Disease Branch of Beijing Medical Association,Chinese Pharmaceutical Association,Beijing Pharmaceutical Association,and the School of Public Health,Peking University have jointly initiated the drafting of the Expert Consensus on Off-label Use of Drugs for Rare Diseases.This consensus refer to the WHO Handbook for Guideline Development,the Guidelines for Developing/Revising Clinical Diagnostic and Treatment Guidelines in China(2022 Edition),the AGREE Ⅱ and the STAR tools.This protocol outlines the background and purpose of consensus,as well as the comprehensive framework for consensus development,encompassing panel formation,clinical issue identification,evidence retrieval,data extraction,and evidence-based recommendation formulation.

By reviewing the historical materia medica， medical books and modern literature， this paper has systematically sorted out and verified the name， origin， quality and other aspects of Ophicalcitum. After herbal textual research， it is shown that before the Qing dynasty， the mineral medicine was mostly recorded in the name of Huarushi， but now it is called Huaruishi， and there is another mixed name Baiyunshi. The light white spots described in the historical materia medica are consistent with the characteristics of marble with sparkling star-like luster， combined with the color like sulfur， color are green， black spots and other serpentine features， it is deduced that it is serpentine marble， consistent with the present-day Ophicalcitum， and Ophicalcitum in the Song dynasty has a high content of serpentine. The main producing areas are Henan， Shaanxi， Shanxi and Sichuan， Jiangsu， Zhejiang， Hebei and other places are also available. Successive generations of materia medica on the quality evaluation of Ophicalcitum is less， the modern to neat and firm in the texture， sandwiched with yellow-green mottled for the best. Ophicalcitum is acidic， astringent and neutral in nature， belonging to the liver meridian， with the efficacy of treatment of gold sores and blood flow， internal leakage of cataracts， dropping afterbirth， now describing its efficacy as removing blood stasis and stopping bleeding. In ancient times， the earliest processing method was burning， followed by calcination by sulphur， calcination， quenching with vinegar and other methods. In modern times， it has been simplified to open calcination， processing with vinegar and the addition of water quenching. The gravimetric method and ethylenediaminetetraacetic acid titration were used to detect the contents of CO₃^2- and CaCO₃ in Ophicalcitum， respectively， and it was found that the gap in CaCO₃ content among commercially available products was wide， and the content of CaCO₃ in sample S13 and sample S18 was the same， but their compositions were different， and according to the contents of CO₃^2- and CaCO₃， the dolomite and calcite contents could be calculated， of which the higher the calcite content the more obvious the sparkling star-like luster. Raman spectroscopy and X-ray diffraction（XRD） were used to detect the physical phase composition of the powder of the samples， and Raman spectroscopy was used for the rapid non-destructive testing of the striped part， which showed that Ophicalcitum was mainly composed of dolomite， calcite， serpentine， olivine and pyroxene， with serpentine dominanting the striped part. In summary， the 2020 edition of Chinese Pharmacopoeia stipulates that the content of CaCO₃ in Ophicalcitum is not less than 40%， which is difficult to control its quality， and it is suggested to increase the detection of CO₃^2- content. This study can provide a scientific basis for the traceability of Ophicalcitum and better guide the clinical medication and rational utilization of resources.

Background and purpose:For patients with human epidermal growth factor receptor 2(HER2)-positive metastatic breast cancer,trastuzumab treatment can prolong the overall survival and significantly improve the prognosis of patients.However,the reference original research trastuzumab(Herceptin?)is more expensive.Biosimilars have comparable efficacy and safety profiles while increasing patient access to treatment.This clinical trial aimed to evaluate the efficacy,pharmacokinetics,safety and immunogenicity of the trastuzumab biosimilar AK-HER2 compared to trastuzumab(Herceptin?)in patients with HER2-positive metastatic breast cancer.Methods:This multi-center,randomised,double-blind phase Ⅲ clinical trial was conducted in 43 subcenters in China.This study complied with the research protocol,the ethical principles stated in the Declaration of Helsinki and the quality management standards for drug clinical trials.It was approved by the hospital's medical ethics committee.The clinical trial registration agency is the State Food and Drug Administration(clinical trial approval number:2015L04224;clinical trial registration number:CTR20170516).Written informed consent was obtained from subjects before enrollment.Enrolled patients were randomly assigned to the AK-HER2 group and the control group,respectively receiving AK-HER2 or trastuzumab(initial loading dose 8 mg/kg,maintenance dose 6 mg/kg,every 3 weeks as a treatment cycle,total treatment time is 16 cycles)in combination with docetaxel(75 mg/m2,treatment duration is at least 9 cycles).The primary endpoint of this clinical trial was the objective response rate(ORR9)between the AK-HER2 group and the control group in the 9th cycle.Secondary efficacy endpoints included ORR16,disease control rate(DCR),clinical benefit rate(CBR),progression-free survival(PFS)and 1-year survival rate.In this study,100 subjects(AK-HER2 group to control group=1:1)were randomly selected for blood sample collection after the 6th cycle of medication,The collection time points were 45 minutes after infusion(the end of administration),4,8,24,72,120,168,336,and 504 hours after the end of administration.After collection,blood samples were analyzed by PK parameter set(PKPS).Other evaluation parameters included safety and immunogenicity assessment.Results:A total of 550 patients with HER2-positive metastatic breast cancer were enrolled in this clinical trial between Sep.2017 and Mar.2021.In the AK-HER2 group(n=237),129 subjects in the experimental group achieved complete response(CR)or partial response(PR),and the ORR9 was 54.4%.There were 134 subjects in the control group(n=241)who achieved CR or PR,and the ORR9 was 55.6%.The ORR9 ratio between the AK-HER2 group and the control group was 97.9%[90%confidence interval(CI):85.4%-112.2%,P=0.784],which was not statistically significant.In all secondary efficacy endpoints,no statistically significant differences were observed between the two groups.We conducted a mean ratio analysis of pharmacokinetics(PK)parameters between the AK-HER2 group and the control group,and the results suggested that the pharmacokinetic characteristics of the two drugs are similar.The incidence of treatment emergent adverse event(TEAE)leading to drug reduction or suspension during trastuzumab treatment was 3.6%(10 cases)in the AK-HER2 group and 8.1%(22 cases)in the control group.There was statistically significant difference between the two groups(P=0.027).The incidence rate was significantly lower in the AK-HER2 group than in the control group,and there was no statistically significant difference among the other groups.The differences in the positive rates of anti-drug antibodies(ADA)and neutralizing antibodies(NAB)between groups were of no statistical significance(P=0.385 and P=0.752).Conclusion:In patients with HER2-positive metastatic breast cancer,AK-HER2 was comparable to the trastuzumab(Herceptin?)in terms of drug efficacy,pharmacokinetics,safety and immunogenicity.

Humans ; Aged ; Lung Diseases ; Pneumonia/drug therapy* ; Adrenal Cortex Hormones/therapeutic use* ; Pulmonary Disease, Chronic Obstructive/drug therapy* ; Administration, Inhalation ; Community-Acquired Infections/drug therapy*

Objective:To investigate the early clinical characteristics of elderly patients with severe burns and the risk factors on prognosis.Methods:This study was a retrospective case series study. Clinical data of 124 elderly patients with severe burns who met the inclusion criteria and were admitted to the 12 hospitals from January 2015 to December 2020 were collected, including 4 patients from the Fourth People's Hospital of Dalian, 5 patients from Fujian Medical University Union Hospital, 22 patients from Guangzhou Red Cross Hospital of Jinan University, 5 patients from Heilongjiang Provincial Hospital, 27 patients from the First Affiliated Hospital of Naval Medical University, 9 patients from the First Affiliated Hospital of Nanchang University, 10 patients from Affiliated Hospital of Nantong University, 9 patients from Tongren Hospital of Wuhan University & Wuhan Third Hospital, 12 patients from the 924 th Hospital of PLA, 6 patients from Zhangjiagang First People's Hospital, 4 patients from Taizhou Hospital of Zhejiang Province, and 11 patients from Zhengzhou First People's Hospital. The patients' overall clinical characteristics, such as gender, age, body mass index, total burn area, full-thickness burn area, inhalation injury, causative factors, whether combined with underlying medical diseases, and admission time after injury were recorded. According to the survival outcome within 28 days after injury, the patients were divided into survival group (89 cases) and death group (35 cases). The following data of patients were compared between the two groups, including the basic data and injuries (the same as the overall clinical characteristics ahead); the coagulation indexes within the first 24 hours of injury such as prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time, D-dimer, fibrinogen degradation product (FDP), international normalized ratio (INR), and fibrinogen; the blood routine indexes within the first 24 hours of injury such as white blood cell count, platelet count, neutrophil-to-lymphocyte ratio, monocyte count, red blood cell count, hemoglobin, and hematocrit; the organ function indexes within the first 24 hours of injury such as direct bilirubin, total bilirubin, urea, serum creatinine, aspartate aminotransferase, alanine aminotransferase, total protein, albumin, globulin, blood glucose, triglyceride, total cholesterol, alkaline phosphatase, creatine kinase, electrolyte indexes (potassium, sodium, chlorine, calcium, magnesium, and phosphorus in blood), uric acid, myoglobin, and brain natriuretic peptide; the infection and blood gas indexes within the first 24 hours of injury such as procalcitonin, C-reactive protein, pH value, oxygenation index, base excess, and lactate; treatment such as whether conducted with mechanical ventilation, whether conducted with continuous renal replacement therapy, whether conducted with anticoagulation therapy, whether applied with vasoactive drugs, and fluid resuscitation. The analysis was conducted to screen the independent risk factors for the mortality within 28 days after injury in elderly patients with severe burns. Results:Among 124 patients, there were 82 males and 42 females, aged 60-97 years, with body mass index of 23.44 (21.09, 25.95) kg/m 2, total burn area of 54.00% (42.00%, 75.00%) total body surface area (TBSA), and full-thickness burn area of 25.00% (10.00%, 40.00%) TBSA. The patients were mainly combined with moderate to severe inhalation injury and caused by flame burns. There were 43 cases with underlying medical diseases. The majority of patients were admitted to the hospital within 8 hours after injury. There were statistically significant differences between patients in the 2 groups in terms of age, total burn area, full-thickness burn area, and inhalation injury, and PT, APTT, D-dimer, FDP, INR, white blood cell count, platelet count, urea, serum creatinine, blood glucose, blood sodium, uric acid, myoglobin, and urine volume within the first 24 hours of injury (with Z values of 2.37, 5.49, 5.26, 5.97, 2.18, 1.95, 2.68, 2.68, 2.51, 2.82, 2.14, 3.40, 5.31, 3.41, 2.35, 3.81, 2.16, and -3.82, respectively, P<0.05); there were statistically significant differences between two groups of patients in whether conducted with mechanical ventilation and whether applied with vasoactive drugs (with χ2 values of 9.44 and 28.50, respectively, P<0.05). Age, total burn area, full-thickness burn area, serum creatinine within the first 24 hours of injury, and APTT within the first 24 hours of injury were the independent risk factors for the mortality within 28 days after injury in elderly patients with severe burns (with odds ratios of 1.17, 1.10, 1.10, 1.09, and 1.27, 95% confidence intervals of 1.03-1.40, 1.04-1.21, 1.05-1.19, 1.05-1.17, and 1.07-1.69, respectively, P<0.05). Conclusions:The elderly patients with severe burns had the injuries mainly from flame burns, often accompanied by moderate to severe inhalation injury and enhanced inflammatory response, elevated blood glucose levels, activated fibrinolysis, and impaired organ function in the early stage, which are associated with their prognosis. Age, total burn area, full-thickness burn area, and serum creatinine and APTT within the first 24 hours of injury are the independent risk factors for death within 28 days after injury in this population.

The robustness of sliding mode control is utilized to improve the adaptability of the control system to changes in vascular mechanical properties of different patients.Adaptive sliding mode control is designed to adapt the controller to the needs of different virtual environment simulations through an adaptive mechanism,thereby weakening the chattering of sliding mode control.The extrapolation prediction algorithm is invoked under the adaptive sliding mode control to reduce the effects of delay on the control and improve force feedback transparency.The experimental results demonstrate that adaptive sliding mode predictive control can enhance system stability,force feedback control accuracy,and fidelity of force feedback control system for flexible surgical instruments.The study has important theoretical significance and practical value for the design of systems with flexible control objects and the improvement of force feedback fidelity.