Tigecycline(TGC)is a recently developed broad-spectrum and highly effective glycylcy-cline antibiotic that overcomes traditional tetracycline resistance mechanisms.It is widely used in the treatment of complex skin and intra-abdominal infections.However,the emergence of TGC re-sistance in recent years poses a significant challenge,and its underlying resistance mechanisms re-main incompletely understood,warranting further investigation.This study induced TGC resistance in Klebsiella aerogenes(ATCC-43864)under in vitro conditions and evaluated phenotypic chan-ges,including growth curves,motility,multidrug susceptibility,and ultrastructural alterations,be-fore and after induction.Whole-genome sequencing(WGS)and transcriptome sequencing(RNA-seq)were employed to analyze resistance-related genetic changes,which were further validated.Ef-flux pump inhibition assays and Red homologous recombination were used to investigate the roles of efflux pumps,lon deletion,and rpsM mutation in TGC resistance.A stable resistant strain,CF-T-32,was obtained,with a 32-fold increase in TGC minimum inhibitory concentration(MIC).CF-T-32 exhibited an enlarged periplasmic space between the cell wall and membrane,reduced growth and motility,and no significant changes in susceptibility to 28 antimicrobial agents,including doxy-cycline,gentamicin,and ciprofloxacin.Genomic analysis revealed no significant differences in ge-nome composition or interference from exogenous plasmids between the parental and induced strains.However,two missense mutations were identified in rpsM and lon.Transcriptomic analysis and qPCR validation showed significant upregulation of efflux pump genes(acrA and acrB)in the AcrAB-TolC system and downregulation of ribosomal protein genes(rpsM,rpsJ,and rpsC).Ef-flux pump inhibition and Red homologous recombination experiments demonstrated that the rpsM C287T missense mutation,leading to a Pro96Leu substitution and reduced expression,is likely the primary factor contributing to TGC resistance in the induced strain.

Objective To study the technological innovation efficiency of the pharmaceutical manufacturing industry and its relationship with industrial development.Methods The data from the China Statistical Yearbook,China High Tech Statistical Yearbook,the statistical yearbook data of regional statistical bureaus was collected to evaluate the technological innovation efficiency of the pharmaceutical manufacturing industry in 29 provinces and cities in China based on the super-efficiency three-stage SBM model.And then,the spatial econometric model and panel quantile regression model were used to conduct empirical research.Results The average technological innovation efficiency of the pharmaceutical manufacturing industry in 29 provinces was 0.49,with the east greater than the central region,and the central region greater than the west.The technological innovation efficiency of pharmaceutical manufacturing industry has a significant positive correlation with its industrial development,and the marginal effect of this effect shows a law of diminishing in regions with low to high development level,and there is a significant positive spatial spillover effect of pharmaceutical manufacturing industry development between regions.Conclusions The central and western provinces,which have relatively weak pharmaceutical manufacturing industries,should improve the innovation environment and talent supply to enhance the efficiency of technological innovation.Concerted efforts should be made to vigorously promote exchanges,connections,and cooperation between regions with strong technological innovation efficiency and their surrounding areas.And it is imperative to encourage top domestic pharmaceutical companies to significantly increase their investment in the research and development of innovative drugs and to actively engage in international competition.

Tigecycline(TGC)is a recently developed broad-spectrum and highly effective glycylcy-cline antibiotic that overcomes traditional tetracycline resistance mechanisms.It is widely used in the treatment of complex skin and intra-abdominal infections.However,the emergence of TGC re-sistance in recent years poses a significant challenge,and its underlying resistance mechanisms re-main incompletely understood,warranting further investigation.This study induced TGC resistance in Klebsiella aerogenes(ATCC-43864)under in vitro conditions and evaluated phenotypic chan-ges,including growth curves,motility,multidrug susceptibility,and ultrastructural alterations,be-fore and after induction.Whole-genome sequencing(WGS)and transcriptome sequencing(RNA-seq)were employed to analyze resistance-related genetic changes,which were further validated.Ef-flux pump inhibition assays and Red homologous recombination were used to investigate the roles of efflux pumps,lon deletion,and rpsM mutation in TGC resistance.A stable resistant strain,CF-T-32,was obtained,with a 32-fold increase in TGC minimum inhibitory concentration(MIC).CF-T-32 exhibited an enlarged periplasmic space between the cell wall and membrane,reduced growth and motility,and no significant changes in susceptibility to 28 antimicrobial agents,including doxy-cycline,gentamicin,and ciprofloxacin.Genomic analysis revealed no significant differences in ge-nome composition or interference from exogenous plasmids between the parental and induced strains.However,two missense mutations were identified in rpsM and lon.Transcriptomic analysis and qPCR validation showed significant upregulation of efflux pump genes(acrA and acrB)in the AcrAB-TolC system and downregulation of ribosomal protein genes(rpsM,rpsJ,and rpsC).Ef-flux pump inhibition and Red homologous recombination experiments demonstrated that the rpsM C287T missense mutation,leading to a Pro96Leu substitution and reduced expression,is likely the primary factor contributing to TGC resistance in the induced strain.

Objective To study the technological innovation efficiency of the pharmaceutical manufacturing industry and its relationship with industrial development.Methods The data from the China Statistical Yearbook,China High Tech Statistical Yearbook,the statistical yearbook data of regional statistical bureaus was collected to evaluate the technological innovation efficiency of the pharmaceutical manufacturing industry in 29 provinces and cities in China based on the super-efficiency three-stage SBM model.And then,the spatial econometric model and panel quantile regression model were used to conduct empirical research.Results The average technological innovation efficiency of the pharmaceutical manufacturing industry in 29 provinces was 0.49,with the east greater than the central region,and the central region greater than the west.The technological innovation efficiency of pharmaceutical manufacturing industry has a significant positive correlation with its industrial development,and the marginal effect of this effect shows a law of diminishing in regions with low to high development level,and there is a significant positive spatial spillover effect of pharmaceutical manufacturing industry development between regions.Conclusions The central and western provinces,which have relatively weak pharmaceutical manufacturing industries,should improve the innovation environment and talent supply to enhance the efficiency of technological innovation.Concerted efforts should be made to vigorously promote exchanges,connections,and cooperation between regions with strong technological innovation efficiency and their surrounding areas.And it is imperative to encourage top domestic pharmaceutical companies to significantly increase their investment in the research and development of innovative drugs and to actively engage in international competition.

Objective To study the efficiency and influencing factors of medical resource allocation in 30 provinces and cities of China.Methods Evaluating the efficiency of medical resource allocation in three regions in Chinese mainland,including 30 provincial administrative regions from 2009 to 2021 using the three-stage DEA-Tobit model.Results After excluding environmental factors,the mean value of the technical efficiency of medical resource allocation in China showed a slight downward trend.Per capita GDP and population density had a generally positive effect on the adjusted efficiency of medical resource allocation.In the eastern and central regions,the per capita GDP had consistent coefficients of 0.09 for the efficiency of medical resource allocation.Conclusion In regions of China where medical resources are relatively abundant,the allocation efficiency is relatively low,such as in Beijing and Tianjin.Conversely,the allocation efficiency is relatively higher in areas where medical resources are less abundant.

Objective To study the relationship between health investment and economic growth in China.Methods An empirical study was conducted using threshold effect models and instrumental variable methods.Results Human capital investment in health sector can promote economic growth more than physical capital investment.Conclusion More human capital investment,such as the number of health personnel,should be added in the future health investment,and physical capital investment,such as the number of beds,should be controlled.The eastern region should increase health investment related to the elderly,which is more conducive to regional economic growth,while the central region should also increase health investment in physical capital such as the number of beds,while the western region should increase health investment in both aspects,which is more conducive to economic growth,because the economic development is relatively slow.

Objective To study the topoanatomy of anterior perineal plane and adjoining tissue structure in the preparation of ultra-low anterior resection of the rectum. Methods Dissection was performed on 16 male cadavers of semi-pelvis sectioned in the saggital plane. Eight indexes were measured and recorded. Results Anterior perineal plane was clearly found in all 16 cadavers. The median distance of rectum-urethra (R-U) was 14 mm (ranging 10 -17 mm). The contour of perineal body was trapezoid,which was narrow cranially and broad caudally. The median width of cranial perineal body was 8 mm (ranging 6 -9 mm), while the median width of caudal perineal body was 21 mm (ranging 18 -23 mm).The median numerus of thickness of perineal body (TPB), thickness of puborectalis (TPR), arrterior wall of rectum (aPR) -D, pPR-D and width of pelvic diaphragm (WPD) were 20. 5 mm ( ranging 17 - 23 mm),12 mm(ranging 10 -16 mm), 25 mm(ranging 21 -27 mm), 20 mm(ranging 16 -23 mm) and 8 mm (ranging 6 - 10 mm) respectively. Conclusions Anterior perineal plane clearly exists, through which about 20 mm more length of the distal rectum is available which could increase the sphincter-saving rate in cases of low rectal carcinoma.

OBJECTIVE:To discuss the reasons of false drug advertisement,and to suggest the countermeasures against it.METHODS:The reasons of false drug advertisement were analyzed by using the knowledge of law,governmental admin?istration and economy.RESULTS&CONCLUSION:The countermeasures against false drug advertisement were suggested.Firstly,the regulations on defining false drug advertisement should be improved.The legal responsibilities should be specified and the punishment on the violators should be more severe.Secondly,the government should strengthen the law enforcement,and establish the credibility system and regulation for claim.Thirdly,the pharmaceutical enterprises should be self-disci?plined,and improve their professional credibility.Fourthly,the governmental departments of business administration should take a strict control on awarding advertisement license to the media.Last but not the least,the consumers should improve their common medical knowledge.

OBJECTIVE:To probe into the economic reasons accountable for government's failure in compulsive drug pricing and put forward the countermeasure on how to strengthen the effect of compulsive pricing of the government.METHODS:Economic model was applied in the deduction and demonstration.RESULTS & CONCLUSIONS:Government's failure in setting compulsive drug prices is rooted from the imperfect pricing system.To strengthen the effect of governmental drug pricing,it is necessary to establish some supporting measures such as to tighten control on drug recommenders,shift from governmental compulsive pricing to governmental authorization to avoid excessive competition,and give reasonable compensations for special drug manufacturers etc.