[Progress on clinical trials of common gastrointestinal cancer drugs in China from 2012 to 2021].

Objective: Systematically summarize the research progress of clinical trials of gastric cancer oncology drugs and the overview of marketed drugs in China from 2012 to 2021, providing data and decision-making evidence for relevant departments. Methods: Based on the registration database of the drug clinical trial registration and information disclosure platform of Food and Drug Administration of China and the data query system of domestic and imported drugs, the information on gastric cancer drug clinical trials, investigational drugs and marketed drugs from January 1, 2012 to December 31, 2021 was analyzed, and the differences between Chinese and foreign enterprises in terms of trial scope, trial phase, treatment lines and drug type, effect and mechanism studies were compared. Results: A total of 114 drug clinical trials related to gastric tumor were registered in China from 2012 to 2021, accounting for 3.7% (114/3 041) of all anticancer drug clinical trials in the same period, the registration number showed a significant growth rate after 2016 and reached its peak with 32 trials in 2020. Among them, 85 (74.6%, 85/114) trials were initiated by Chinese pharmaceutical enterprise. Compared with foreign pharmaceutical enterprise, Chinese pharmaceutical enterprise had higher rates of phase I trials (35.3% vs 6.9%, P=0.001), but the rate of international multicenter trials (11.9% vs 67.9%, P<0.001) was relatively low. There were 76 different drugs involved in relevant clinical trials, of which 65 (85.5%) were targeted drugs. For targeted drugs, HER2 is the most common one (14 types), followed by PD-1 and multi-target VEGER. In the past ten years, 3 of 4 marketed drugs for gastric cancer treatment were domestic and included in the national medical insurance directory. Conclusions: From 2012 to 2021, China has made some progress in drug research and development for gastric carcinoma. However, compared with the serious disease burden, it is still insufficient. Targeted strengthening of research and development of investment in many aspects of gastric cancer drugs, such as new target discovery, matured target excavating, combination drug development and early line therapy promotion, is the key work in the future, especially for domestic companies.

[Comparative electron microscopy study of Leishmania major and L. tropica in experimental infestation of the sandfly Phlebotomus papatasi]. / Sravnitel'noe élektronno-mikroskopicheskoe izuchenie Leishmania major i L. tropica pri éksperimental'nom zarazhenii moskita Phlebotomus papatasi.

For the first time comparative study was conducted of the ultrastructure of promastigotes of Leishmania major and L. tropica in the organism of Phlebotomus papatasi which for the first species of Leishmania is and for the second species is not a natural invertebrate host. During the bloodsucking on Mesocricetus auratus experimentally infected with Leishmania sandflies perceive amastigotes of both L. major and L. tropica. In the midgut of the sandfly both species of Leishmania pass into the stage of promastigote (therefore, this phenomenon is not defined by species-specific factors). However, further fate of promastigotes of L. major and L. tropica in Ph. papatasi is different. L. major has its normal cycle of development in the intestine of the sandfly and preserves its all ultrastructural peculiarities. Promastigotes of L. tropica, on the contrary, display in the midgut of Ph. papatasi signs of degeneration which are expressed in break of their normal ultrastructure (changes in the shape of cells, break in cell division, thickening or thinning of intracytoplasmatic formations, especially of mitochondria, intensified vacuolisation of cytoplasm, changes in the structure of nucleus and kinetoplast; and others). All these data indicate in an indirect way that the intestine of Ph. papatasi is a favourable medium for L. major and unfavourable one for L. tropica.

[A comparative study of ultrastructural organization of the nonagglutinating vibrios and the causative agents of cholera]. / Sravnitel'noe izuchenie ul'trastrukturnoi organizatsii neaggliutiniruiushchikhsia vibrinovov i vozbuditelei kholery

A common plan of ultrastructural organization was revealed in a comparative study of the ultrastructure of the nonagglutinating El Tor and cholera vibrios: the presence of a three-layer cell wall and cytoplasmic membrane, the presence of vesicles on the external layer of the cell wall or between the cell wall and the cytoplasmic membrane; identity of the intracytoplasmic membranous structures; the presence of intracytoplasmic inclusions in the form of granules of various size and electron density; cell division by means of a band with the formation of two cells of equal size or of many bands in one cell, and also by the joining of the cytoplasmic membrane with the formation of rings at the sites of cell division. Identify of the ultrastructure of the vibrios under study can serve as confirmation of the views of the investigators who consider that nonagglutinating vibrios should be referred to a single V. cholerae species.

[Ultrastructure of L forms. IV. L forms of nonagglutinating vibrios]. / Ul'trastruktura L-form. Soobshchenie IV. L-formy neaggliutiniruiushchikh vibrionov

A study was made of the ultrastructure of stable L-forms of Nag vibrios aged 24 hours. Cells of all types of the L-forms had cytoplasmic membranes, and a three-layered structure, which was found not everywhere. Externally of the cytoplasmic membrane, in some areas of the individual cells there were revealed a plastic layer of cell wall and a basal membrane. However, in difference to bacterial forms of the vibryos, rigidity of the cell wall was disturbed, and the links between the cell wall and the cytoplasmic membrane were indetectable. There were regularly revealed lamellar of myelin-like membranous structures in the cytoplasm, which did not occur in bacterial forms, and also lamellar mesosomes. The latter were found in the sites of cell division. Viability of small bodies as the minimal reproductive forms of the L-cultures is confirmed by the presence in them of a nucleoid and of the binary division.