OBJECTIVE:To provide reference for improving the drug price regulation policy in China. METHODS:Literature research,system comparison and other methods were used to summarize the commonalities and characteristics of drug price regula-tion policy in Germany,Japan and Taiwan area of China,and the successful experience was learned. RESULTS & CONCLU-SIONS:Drug price management in Germany,Japan and Taiwan area of China has their own characteristics. Germany conducted reference price system and new drug pricing mechanism,which was the first country to introduce the reference price system. Japan granted price premiums to innovative drugs,decreased pricing for generic drugs and adjusted drug price again. And Taiwan area of China classified and grouped differential pricing to encourage competition negotiation and regularly investigated drug prices and pric-ing. Germany,Japan and Taiwan area regard medicare pay price as core of drug price management,adopt comprehensive means to regulate the drug price,and pay attention to the monitoring and regular adjustment of market price as well. Price negotiation,phar-macoeconomics and multiple pricing methods are broadly used. Value-based drug pricing system is new trend of price policy re-form. It can be used for reference to improve the drug price regulation system in China.

Objective To explore the pathogen spectrum, drug resistance rate and clinical characteristics of pneumonia caused by non-tuberculous mycobacteria (NTM) in acquined immuno-deficiency syndrome (AIDS) patients.Methods The clinical data of 31 hospitalized AIDS patients with bronchoalceolar lavage flind (BALF) culture confirmed NTM pulmonary disease in Guangzhou No.8 People′s Hospital from January,2008 to February,2015 were retrospectively analyzed, including pathogen spectrum, drug resistance rate and clinical characteristics.The clinical characteristics and drug resistance were compared between Mycobacterium avmm-intracellulare complex (MAC) pneumonia and the non-MAC pneumonia, and t test and chi-square test were used.Results Of the 31 AIDS patients,28 were male and 3 were female, with the mean age of 40.9 years old.The 31 NTM strains were consisted of 14 MAC strains and 17 non-MAC strains (including 4 M.kansasii strains,3 M.lentiflavumstrains, 2 M.szulgai strains, 2 M.yongonense strains etc).There was no significant difference between two groups in sex ratio, mean age, clinical manifestations, laboratory tests and treatment outcome (all P>0.05).The major clinical manifestations included fever, productive cough, weight loss, anemia and low CD4+ count (<50/μL).Most patients showed thoracic lymphadenectasis and patchy shadows in lungs, and few patients had millet shadows and pericardial effusion.Compared with non-MAC strains, MAC strains had higher drug resistant rate of moxifloxacin (10/14 vs 4/17), levofloxacin (14/14 vs 8/17), and clarithromycin (11/14 vs 7/17).More extensively drug resistance strains were seen in non-MAC strains compared with MAC strains (11/14 vs 7/17).Conclusions MAC is the most common pathogen of NTM pulmonary disease in AIDS patients.The clinical features of pneumonia caused by MAC and non-MAC are similar, but drug resistance of MAC strains are more severe.

OBJECTIVE:To provide reference for dynamic adjustment of low-cost medicine lists and better guarantee of low-cost supply in those provinces,autonomous regions and municipalities[referred to provinces(autonomous regions or municipali-ties)]. METHODS:The varieties and frequency of medicines in the national and 31 province(autonomous regions or municipali-ties) lists were counted,and the influential factors were analyzed. RESULTS:The National Low-cost Medicine List included 533 varieties of medicines,including 283 western medicines,250 Chinese patent medicines and 60 exclusive varieties. There were total-ly 973 varieties of medicines in the 31 province(autonomous regions or municipalities),including 332 western medicines,630 Chi-nese patent medicines,11 ethnic medicines and 71 protected Chinese medicines. There was no big difference in the varieties be-tween the eastern and western areas,and less in the central areas. Guangxi province had the largest number of selected medicines (345 varieties) and Jiangxi province had the smallest (10 varieties). In all the varieties,Chinese medicines had a larger number than western medicines,and also better concentration. Ketotifen was the most frequent western medicine and Tongbianling capsule was the most frequent Chinese patent medicine,which appeared 30 and 29 times separately. The Provincial Low-cost Medicine Lists and the Essential Medicine Supplement Lists had a poor coincidence rate,and there was a moderate correlation between the varieties and the number of pharmaceutical manufacturers in the province(autonomous regions or municipalities). CONCLUSIONS:The adjustment of low-cost medicine lists should be combined with these in province(autonomous regions or municipalities) near-by,and notice the linkage with national essential medicine system to fundamentally ensure the clinical medication requirements of patients.

Objective:To analyze the clinical features of acquired immunodeficiency syndrome (AIDS) patients complicated with peripulmonary occupational lesions.Methods:Fifty-five AIDS patients with peripulmonary occupational lesions treated in Guangzhou Eighth People′s Hospital from January 2012 to January 2019 were included, and the clinical data of patients were retrospectively analyzed. According to the results of lung biopsy, the patients were divided into Mycobacterium infection group, fungal infection group and tumor group. The clinical characteristics, the proportion of different CD4 + T lymphocyte counts and chest computed tomography (CT) features of the three groups were compared. Chi square test was used for comparison among the three groups, and Bonferroni method was used to correct the test level for pairwise comparison. The significance level was 0.016 7 because of three pairwise comparisons. Results:Among 55 AIDS patients complicated with peripulmonary occupational lesions, pulmonary biopsy showed 14 cases with Mycobacterium infection, 12 cases with fungal infection and 15 cases with tumor lesions. Mixed diseases were found in 11 patients, including seven cases with Mycobacterium and fungus coinfection, four with tumor complicated with fungus and (or) Mycobacterium. Three with chronic interstitial pneumonia. The main clinical manifestations of 55 patients were fever, expectoration, fatigue, weight loss and superficial lymph node enlargement. There were no significant differences in symptoms/signs, white blood cell counts, hemoglobin levels, alanine transaminase and creatinine among Mycobacterium infection group, fungal infection group and tumor group (all P>0.05). There was significant difference in anti-retroviral therapy (ART) acceptance among the three groups ( χ2=15.165, P<0.01). However, the results of pairwise comparison between groups showed that there was significant difference between fungal infection group and tumor group ( χ2=7.514, P<0.016 7), while there was no significant difference between Mycobacterium infection group and tumor group, Mycobacterium infection group and fungal infection group ( χ2=0.255 and 5.306, respectively, both P>0.016 7). There were significant differences in clinical outcomes among the three groups ( χ2=15.119, P<0.01), and the pairwise comparison between the Mycobacterium infection group and the tumor group, and the fungal infection group and the tumor group showed significant differences ( χ2 =10.311 and 9.095, respectively, both P<0.016 7). The cases with CD4 + T lymphocyte count ≤50/μL, 51-<200/μL and ≥200/μL in Mycobacterium infection group were three cases, one case and 10 cases, respectively; those in fungal infection group were 10 cases, two cases and 0 case, respectively, and those in tumor group were one case, two cases and 12 cases, respectively. The difference was statistically significant ( χ2=21.284, P<0.01). Chest CT showed that there was significant difference in the types of space occupying lesions among the three groups ( χ2=13.308, P=0.003), and pairwise comparison between the two groups showed that there was significant difference between the Mycobacterium infection group and the tumor group ( χ2=11.312, P<0.016 7), while there were no significant differences between the Mycobacterium infection group and fungal infection group ( χ2=0.931, P>0.016 7), and the fungal infection group and the tumor group ( χ2=7.053, P>0.016 7). There was significant difference among the three groups in calcification focus ( χ2=8.524, P=0.004), while there was no difference between the Mycobacterium infection group and fungal infection+ tumor group ( χ2=10.982, P<0.016 7). Conclusions:Mycobacterium infection, fungal infection and tumor are the main types of peripulmonary occupational lesions in AIDS patients. The differential diagnosis could be made by combining with chest CT features, ART acceptance and CD4 + T lymphocyte level.

Objective To investigate the characteristics of mycobacteria species distribution in human immunodeficiency virus (HIV)-positive patients co-infected with mycobacteria in Guangzhou. Methods A total of 133 mycobacteria strains isolated from HIV-positive patients and 150 strains isolated from HIV-negative patients were included in this study. After DNA extraction of mycobacteria, mycobacteria species identification was performed by sequencing of multiple genes.Differences in the identified species were compared between patients with and without HIV infection and the correlation between CD4 + T cells level and the mycobacterial species distribution was analyzed.Chi-square test was used for statistical analysis.Results Of the 133 mycobacteria strains isolated from HIV-positive patients, 82 were identified as Mycobacterium tuberculosis complex (MTC ). Fifty-one were identified as nontuberculous mycobacteria (NTM),of which the main species was Mycobacterium avium complex (MAC,31/51).Of the 150 mycobacteria strains isolated from HIV-negative patients,126 were identified as MTC and 24 as NTM,of which the main species was Mycobacterium abscessus (9/24).In patients with CD4 + T cell counts ≤100/μL,the positive rate of mycobacteria was 75 .94%(101/133),93.55 %(29/31) of MAC and 85 .00%(17/20)of other NTM.When the CD4 + T cell counts >100/μL,the positive rate for mycobacteria were all obviously decreased.Conclusions The proportion of NTM infection is higher in HIV-positive patients than HIV-negative patients in Guangzhou. Among HIV-positive patients > the most prevalent NTM species is MAC, while Mycobacterium abscessus is the most common species in HIVnegative patients. Mycobacterial infection in acquired immunodeficiency syndrome patients is closely associated with low CD4+ cells level.

Objective:To analyze the evolution path and diffusion mechanism of the unified drug management system of countywide medical communities in China, and provide references for the deepening implementation of the system.Methods:The policy documents of the central and provincial governments were retrieved with the keywords of " medical community" " drug management" " county-township-village integration" and " central pharmacy". By means of the policy diffusion theory, the evolution path of the diffusion of the unified drug management system for the countywide medical communities was identified from such dimensions as time, space and hierarchy. On the other hand, the action mechanism of the diffusion of the system was summarized from such aspects as competition, administrative instruction, learning and imitation.Results:A total of 36 effective policy documents were collected. The time diffusion of the drug unified management system of countywide medical communities was characterized by an " S" curve. By the end of 2022, there were 30 provinces implementing the countywide medical community drug unified management system, and the policy diffusion has entered a saturation and stagnation stage; spatial diffusion showed " proximity effect" ; hierarchy diffusion embodied the " leader follower" mode. In the process of policy diffusion, competition mechanism, administrative instruction mechanism, learning mechanism, and imitation mechanism coexisted, but there were difference in the dominant mechanism at different stages of policy diffusion.Conclusions:The unified drug management system of the countywide medical communities has been widely disseminated. It is recommended to promote the introduction of supporting policies, optimize the system evaluation system, and comprehensively use various diffusion mechanisms to promote the optimization of the system, so as to promote the deepening and sustainable operation of the system.

Mechanistic target of rapamycin (mTOR) complex 1 (mTORC1) integrates signals from growth factors, cellular energy levels, stress and amino acids to control cell growth and proliferation through regulating translation, autophagy and metabolism. Here we determined the cryo-electron microscopy structure of human mTORC1 at 4.4 Å resolution. The mTORC1 comprises a dimer of heterotrimer (mTOR-Raptor-mLST8) mediated by the mTOR protein. The complex adopts a hollow rhomboid shape with 2-fold symmetry. Notably, mTORC1 shows intrinsic conformational dynamics. Within the complex, the conserved N-terminal caspase-like domain of Raptor faces toward the catalytic cavity of the kinase domain of mTOR. Raptor shows no caspase activity and therefore may bind to TOS motif for substrate recognition. Structural analysis indicates that FKBP12-Rapamycin may generate steric hindrance for substrate entry to the catalytic cavity of mTORC1. The structure provides a basis to understand the assembly of mTORC1 and a framework to characterize the regulatory mechanism of mTORC1 pathway.
Cell Line ; Cryoelectron Microscopy ; methods ; Humans ; Mechanistic Target of Rapamycin Complex 1 ; Multiprotein Complexes ; chemistry ; ultrastructure ; Protein Structure, Quaternary ; TOR Serine-Threonine Kinases ; chemistry ; ultrastructure

Transcription, Genetic