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Objective:To investigate the efficacy and adverse reactions of immunotherapy in elderly patients(≥65 years old)with lung squamous cell carcinoma(LUSC)in Chinese population of real world.Methods:A total of 113 elderly LUSC patients(age ≥65 years old)underwent pathological diagnosis were involved from January 2018 to January 2022.To compare the efficacy of mono-immunotherapy or combined with chemotherapy to chemotherapy in first-line and second-line treatment.44 patients received surgical or minimally invasive treatment, and 69 patients received first-line medical treatment, including 27 patients in chemotherapy group, 24 patients in combined chemotherapy group, and 11 patients in single drug immunization group.7 cases in targeted therapy group.Twenty-eight patients received second-line medical treatment, including 8 patients in chemotherapy group, 11 patients in combined immunochemotherapy(combined group), 4 patients in single drug immunotherapy group, and 5 patients in targeted therapy group.The therapeutic effects and adverse reactions were compared between the first-line and second-line treatments.The expression of programmed death-ligand 1(PD-L1)and tumor mutational burden(TMB)were evaluated.Response evaluation criteria in solid tumors(RECIST)version 1.1 was used to evaluate the efficacy, and common terminology criteria for adverse events(CTCAE)version 4.03 was used to evaluate immune-related adverse.Kaplan-meier and log-rank test was performed.Cox regression was used in prognostic analysis.Results:The total effective rate in the first-line combination group was 73.7%(14/19), higher than that in the chemotherapy group(24.0%, 6/25), and the difference was statistically significant( χ2=10.748, P<0.01). Median progression-free survival(mPFS)was longer in the first-line combination group, the immunization group, and the chemotherapy group, and the median overall survival(mOS)was longer in the combination group, but the differences were not statistically significant(all P<0.05); mOS in the second-line combined group were longer than those in the chemotherapy group, both P<0.01). Elderly patients with lung squamous cell carcinoma had high PD-L1 positive rate(≥1%)and high TMB expression rate(≥9 mut/Mb), 81.6%(31/38)and 57.4%(31/54), respectively.mPFS in the PD-L1 positive group(≥1%)was better than that in the PD-L1 negative group(5.10 months vs.0.93 months, P<0.05). Among PD-L1 positive patients, mPFS in the second-line combination group was better than that in the chemotherapy group(7.33 months vs.2.77 months, P<0.05). mPFS and mOS time were not related to TMB expression.The overall incidence of immune-related adverse reactions was 62.0%(31/50), and 26.0%(13/50)with grade 3 or above.The most common grade 3 adverse events were rash, immune-associated pneumonia, and fatigue. Conclusions:Immunology combined with chemotherapy increased objective response rate, mPFS and mOS of elderly patients with LUSC group in first-line therapy compared with chemotherapy.In second-line treatment, the mOS was significantly prolonged in both combination therapy and mono-immunotherapy, and the combination therapy exhibited no benefit in OS compared with monotherapy.The adverse effects of immunology in elderly patients with LUSC were controllable.
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BACKGROUND@#Immune checkpoint inhibitors (ICIs) improved survival of partial patients with lung squamous cell carcinoma (LUSC). However, it was still insufficient of data in older patients. This study aimed to investigate the efficacy and toxicity of immunotherapy in patients with LUSC in Chinese population of real world.@*METHODS@#A total of 185 LUSC patients underwent pathological diagnosis were involved from January 2018 to January 2022. Patients were divided into elderly group (age ≥70 years) and younger group (age <70 years). The efficacy of mono-immunotherapy or combined with chemotherapy to chemotherapy in first-line treatment was compared. The expression of programmed cell death ligand 1 (PD-L1) and tumor mutational burden (TMB) were evaluated. Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 was used to evaluate the efficacy, and Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 was used to evaluate immune-related adverse. Kaplan-Meier and Log-rank test was performed. Cox regression was used in prognostic analysis.@*RESULTS@#Combined therapy acquired significantly higher overall response rate (ORR) compared with chemotherapy alone in elderly group (P<0.05), and also in younger group, despite the difference was not significant (P>0.05). The median progression-free survival (mPFS) and median overall survival (mOS) in elderly group were similar with younger group (P>0.05). Both combined group and immunology alone demonstrated prolonged mPFS in first-line compared with chemotherapy in elderly group. And combined group demonstrated significantly prolonged mPFS compared with chemotherapy in younger group (P<0.01). There was no difference of mOS between different regimes in two groups. Elderly LUSC patients had higher PD-L1 positive rate (≥1%) and similar TMB compared with younger group. There was no relationship between mPFS and mOS with the expression of PD-L1 and TMB. Immunology combined with chemotherapy demonstrated better mPFS compared to chemotherapy in first-line therapy with TMB-High (P<0.05), and inferior mPFS with TMB-Low despite the difference was not significant (P>0.05). Cox regression model demonstrated that clinical stage was an independent predictor and prognostic factor. The incidence of immune-related adverse was 58.0% (51/88) and grade 3 or above 25.0% (22/88). The most common grade 3 adverse events were rash, immune-associated pneumonia, and fatigue.@*CONCLUSIONS@#Immunology combined with chemotherapy increased ORR, mPFS and mOS of Chinese patients with LUSC in first-line therapy compared with chemotherapy. There was no difference of efficacy and adverse effects rate between elderly group and younger group. The adverse effects of immunology in elderly patients with LUSC were controllable.
Subject(s)
Aged , Humans , B7-H1 Antigen/analysis , Biomarkers, Tumor , Carcinoma, Non-Small-Cell Lung/pathology , Carcinoma, Squamous Cell/drug therapy , China , Lung/pathology , Lung Neoplasms/pathologyABSTRACT
Objective:Immunologic characteristics of differed between younger and older patients.This study aimed to screen potentially key genes related to tumor-infiltrated immune cells(TIICs)in senile patients with lung adenocarcinoma(LUAD).Methods:In this retrospective study, the gene expression data for the training set were extracted from the Cancer Genome Atlas(TCGA)database, and the GSE72094 data set from Gene Expression Database was selected as the validation set.The 91 LUAD patients aged ≥75 years and 14 matched normal samples were screened for analysis.The components of tumor infiltrated immune cells(TIICs)were estimated by the deconvolution algorithm.Then a weighted gene co-expression network analysis was conducted in the training set so as to identify key genes correlating to TIICs.The GSE72094 dataset was used for validation.Results:In elderly patients with LUAD, the high expressions of IKZF1 and PRKCB were related to autoimmune diseases and T cell receptor signaling pathway.And their gene encoding proteins could interact with various immunomodulatory factors, such as IL2RB, LCK, and CD5.In the high expression group of IKZF1 and PRKCB, the expression levels of immunological checkpoint genes such as PD-L1, PD-1 and CTLA-4 were significantly higher than those of the low expression group(all P<0.01). The results of the validation set showed that CD8 + T cells were significantly correlated with the expression of IKZF1( r=0.75, P<0.01)and PRKCB( r=0.65, P<0.01). Conclusions:The expressions of IKZF1 and PRKCB in the tumor tissues are related to tumor infiltrating CD8 T cells and expression of immune checkpoint genes in elderly patients with LUAD.
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OBJECTIVE： To investigate the status of sulfur fumigation of TCM and its decoction pieces， and to put forward the suggestions on limit standard of sulfur dioxide residue. METHODS： The information of 374 varieties of TCM and sulfur dioxide residue were collected from the provincial and municipal drug inspection institutions of 27 provinces，municipalities and autonomous regions in China during 2013-2017， and then summarized and analyzed. The average value，median value，maximum value，qualification rate and detection rate of sulfur dioxide residue of 121 varieties with the sample number ≥10 batches were classified and statistically analyzed. RESULTS： This investigation involved 374 varieties of TCM and its decoction pieces， and a total of 13 776 batches of samples. The average content of sulfur dioxide was 242 mg/kg，the median value was 27 mg/kg，and the maximum value was 8 782 mg/kg. The overall qualified rate was 79.7％. According to the results of classified statistics， among the 10 varieties whose limit shall not exceed 400 mg/kg，5 varieties，including Codonopsis pilosula， Radix Trichosanthis， Asparagus cochinchinensis， Pueraria lobata， Achyranthes bidentata， were seriously affected by sulfur fumigation，and the qualified rate was less than 80％. Among the varieties with the sample number≥30 batches， there was no or very little abuse of sulfur fumigation in 16 varieties， such as Carthamus tinctorius； 19 varieties， such as Eupolyphaga Steleophaga， had excessive sulfur fumigation， but it was not serious； 25 varieties，such as Lonicera japonica，had severe excessive sulfur fumigation. Among the varieties with the sample number of 10-29 batches，33 varieties including Ziziphus jujube seed had no or very little abuse of sulfur fumigation； 8 varieties including Cuscuta chinensis had excessive sulfur fumigation but were not serious； 10 varieties including Pericarpium Trichosanthis had serious excessive sulfur fumigation. CONCLUSIONS： For the varieties with no or very little excessive sulfur fumigation，it is recommended that batch testing should not be carried out and a single list should be made； for the varieties with sulfur fumigation or severe sulfur fumigation， it is suggested to increase the sulfur dioxide residue limit under all varieties in the 2020 edition of Chinese Pharmacopoeia， and set the limit for the varieties with severe sulfur fumigation to be no more than 400 mg/kg，while the limit for the 2025 edition of Chinese Pharmacopoeia can be reduced to no more than 150 mg/kg. Other varieties should retain the provisions of “sulfur dioxide residue of sulfur dioxide medicinal materials and decoction pieces （except for minerals） shall not exceed 150 mg/kg” in the general rules 0212 “for the identification of medicinal materials and decoction pieces” in the 2015 edition of Chinese Pharmacopoeia （part Ⅳ）.
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<p><b>OBJECTIVE</b>To provide a reference for the standardization of Tibetan medicine.</p><p><b>METHOD</b>Investigating the hospital preparations , Tibetan formulated products, and the literature recorded preparations in the Tibetan, Qinghai, Gansu, Sichuan and Yunnan Provinces. Moreover, the varieties, original bases and standard conditions of these preparations were analyzed. According to Chinese Pharmacopoeia, Tibetan medicine part of ministerial standard, Tibetan medicine standards and related monographs and literatures of Tibetan medicine.</p><p><b>RESULT</b>About 502 various of herbs were used in 711 hospital preparations from 40 medical institutions, Tibetan formulated products from Tibetan pharmaceutical factories, and 439 literature recorded preparations. About 154 herbs were used in more than 10 preparations, while most of them were Tibetan endemic species. About 416 medicinal varieties have the original documented basis, including 287 botanicals, 78 animal medicines, 51 mineral medicines, involving a total of 94 families, 261 genus and 643 species of botanical origin (including species of the next grade), 35 families, 52 genera and 61 species of the animal origin (including species of the next grade). About 122 varieties of herbs were cross-used in the traditional Chinese medicine and Tibetan medicine, about 80% of Tibetan medicinal varieties are produced in the Tibetan Areas of Tibet Plateau. About 293 medicinal varieties were contained in the above standards. Most of the herb's standards only contains character, indentification, and examination, except for 8 varieties which were recorded in the Chinese Pharmacopoeia (2010) as Tibetan medicine.</p><p><b>CONCLUSION</b>This study of quality standard of Tibetan medicine should have an emphasis on the general varieties, especially the study on the arrangement research and the efficacious material basis of the varieties and the original, as well as term standardization of the National Medicine.</p>
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Animals , Humans , Drugs, Chinese Herbal , Reference Standards , Medicine, Tibetan Traditional , Reference Standards , Plants, Medicinal , ChemistryABSTRACT
The application of the compound preparation of traditional Chinese medicine (TCM) and chemical drug in clinical has a long history. Drug regulatory requirements of the compound preparation of TCM and chemical drug in various periods were compared and analyzed, and the history and status of the way of scientific supervision of this preparation were summarized. This paper discussed the problems and deficiencies of the compound preparation of TCM and chemical drug, and put forward countermeasures and suggestions about to strengthen the scientific supervision of the compound preparation of TCM and chemical drug.
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Humans , Drugs, Chinese Herbal , Medicine, Chinese Traditional , Reference Standards , Pharmaceutical Preparations , Reference StandardsABSTRACT
The prepared slices of Chinese crude drugs are growing important in recent years, and faced with new developments and opportunities. The author analyzed the importance of formulate national processing procedures of prepared slices of Chinese crude drugs combined actual work, proposed the overall objectives and tasks for the formulation, and emphasized to need to correctly deal with several important factors during the process of formulate "National processing procedures of prepared slices of Chinese crude drugs", unified the national standards of prepared slices, solved the real problems that the prepared slices of Chinese crude drugs industry faced.