Objective To establish the HPLC analysis method for ketoconazole related substances,and to provide technical support for the improvement of the quality standard and the purity of ketoconazole.Methods Gradient elution conditions were optimized based on the chromatographic parameters outlined in the 2024"British Pharmacopoeia"for ketoconazole cream.A C18 column(4.6 mm×150 mm,3 μm)was used to facilitate the elution process using a gradient of acetonitrile and acetate buffer,and detection performed at a wavelength of 230 nm.Results The known impurities and potentially genotoxic impurities in the material drugs of ketoconazole can be more effectively separated using the established methods,which are both robust and highly sensitive.The content of the two potentially geno toxic impurities,six known impurities and unknown impurities in the 21 batches of ketoconazole sourced from five raw material pharmaceutical companies is below the specified limit requirements.Conclusion This method contributes to improving the quality of ketoconazole ingredients,ensuring the safety of ketoconazole preparations,and better supporting the regulatory supervision.

OBJECTIVE To investigate the quality and management of cleaning and disinfection of soft endoscopes in Wuxi hospitals,to analyze the existing problems and put forward suggestions for improvement,and to provide references for endoscope-related infection in hospitals.METHODS From Sep.to Nov.2024,the cleaning and disin-fection status and managements of soft endoscopes were investigated.Endoscopes were sampling for adenosine triphosphate(ATP)biofluorescence and bacteriological testing;final rinsing water,hands of disinfection person-nels,disinfectants and environmental surfaces were collected for bacteriological testing.RESULTS Totally 68.18％of hospitals performed daily leaks test before cleaning,and 81.82％used o-Phthalaldehyde;81.25％of hospitals used peracetic acid in endoscopy sterilization,with only 1 hospital using glutaraldehyde.Totally 86.36％of hospi-tals monitored the concentration of disinfectants before daily works.There were statistically significant differ-ences in full-time,education levels,age and working experience of personnels among different levels of hospitals(P＜0.05).The pass rate of the 60 endoscope ATP specimens was 88.33％,and there were statistically signifi-cant differences in the pass rate of gastroscopic ATP testing among different levels of hospitals(P=0.032).The qualification status differed significantly in the types of endoscopes and the time length of enzyme washing(P＜0.05).All 60 endoscopic bacteriological samples were qualified,while 141 environmental bacteriological samples were with a pass rate of 94.33％.Unqualified samples were mainly for disinfection personnel's hands,rinse tank faucets,final rinse water.Rolestonella piercei and Staphylococcus wolffii were detected in one failed final rinse wa-ter by mass spectrometry.CONCLUSIONS The overall equipment and staffing of the surveyed endoscope centers(rooms)basically meet operational needs and generally follow endoscope cleaning and disinfection guidelines.However,there are still deficiencies in cleaning and disinfection management,equipment maintenance,disinfect-ant concentration monitoring and personnel training.Further efforts are needed to strengthen the disinfection quali-ty monitoring of endoscope and related factors.

Aim To evaluate the ameliorative effects of different ratios of Renshen-Huangjing(RH) on SPS-induced PTSD-like behaviors in mice,and to investi-gate the action mechanism using bioinformatics analysis and experimental studies.Methods The aqueous ex-tract was extracted in four ratios of RH in a total weight of 60 g,i.e.1∶0(RH1),2∶1(RH2),1∶2(RH3),and 0∶1(RH4).The extraction rates of Rg1,Rb1,and polysaccharides from different ratios of RH were then detected using UPLC-UV method.The SPS model was established,and RH1,RH2,RH3 and RH4(400 mg·kg-1)were administered by intragas-tric gavage for 14 day,followed by behavioral tests to e-valuate the PTSD-like behaviors.The serum CORT,IL-1β and IL-10 were determined by ELISA.The possible targets of action were analyzed using bioinformatics.The expression levels of Calpain-1,PSD95,BDNF and GluN2B in the hippocampus were detected by Western blot.Results The SPS model induced PTSD-like be-haviors in mice.Serum levels of CORT and IL-1β in-creased and level of IL-10 decreased in SPS model.After treatment with different ratios of RHs,RH2 showed the best therapeutic effect,which was manifes-ted in the suppression of PTSD-like behaviors,the re-duction of CORT and IL-1β levels,and the promotion of IL-10 levels;160 overlapping targets might explain the therapeutic effects of RH on PTSD,and these tar-gets were enriched in inhibiting synaptic damage,exer-ting antioxidant properties and suppressing neuroin-flammation,respectively.RH2 prevented the SPS-in-duced decrease in the expression of Calpain-1,PSD95,BDNF and the elevation of GluN2B.Molecular docking showed strong binding of Rg1 and Rb1 to Calpain-1,PSD95,and BDNF,respectively.Conclusions The a-queous extract of RH in a 2∶1 ratio can more effec-tively prevent SPS-induced PTSD-like behaviors,and its effect may be related to targets such as Calpain-1,PSD95,BDNF and GluN2B.

Aim To systematically investigate the ac-tive components,targets,and regulatory pathways of Po-lygonum capitatum in intervening atherosclerosis(AS)through network pharmacology,molecular docking and animal experiments.Methods Active components of Polygonum capitatum and AS-related targets were screened and identified through database searches.Protein-protein interaction(PPI)network analysis was performed using the STRING database,followed by GO and KEGG enrichment analyses via the David plat-form.Molecular docking validation was conducted with AutoDock.An AS model was established in Syrian golden hamsters fed a high-fat diet.Predicted pathways and targets were validated using qPCR,ELISA,and histopathological assessment of aortic and hepatic tis-sues via HE staining.Results Network pharmacology identified 27 potential active components of Polygonum capitatum(primarily flavonoids such as quercetin and luteolin)and 110 drug-disease intersection targets,in-cluding core targets MMP-9,ALB,and AKT1.GO and KEGG analyses enriched 593 and 125 pathways,re-spectively,with the NF-κB inflammatory pathway,TNF signaling pathway and lipid metabolism/atherosclerosis pathways highlighted as key mechanisms.Animal ex-periments demonstrated that Polygonum capitatum im-proved serum lipid profiles(reduced TC,TG,LDL-C)in AS hamsters,suppressed the MMP-9/NF-κB signa-ling pathway(downregulated MMP-9,p65 phosphoryla-tion,TNF-α,and IL-6),and inhibited VSMC synthetic phenotypic transformation(upregulated α-SMA and myocardin)by downregulating MCPIP1.Additionally,Polygonum capitatum ameliorated aortic lesions and he-patic lipid deposition in AS hamsters.Conclusions Polygonum capitatum alleviates AS by synergistically regulating the MMP-9/NF-κB/MCPIP1 axis through flavonoid components,suppressing vascular inflammato-ry cascades and maintaining VSMC contractile pheno-types.This reflects Polygonum capitatum's multi-com-ponent,multi-pathway,and multi-target characteristics in combating AS.

Objective To understand the impact of bed-making manipulation on the air surrounding bed units in hemodialysis room,evaluate the effectiveness of routine terminal disinfection,and provide scientific basis for optimi-zing infection control measures.Methods Air specimens(pre-bed-making group)and environmental object surface specimens(pre-terminal disinfection group)around bed units were collected when hemodialysis was about to be fi-nished.Air specimens after bed-making(bed-making group)and environmental object surface specimens after ter-minal disinfection(terminal disinfection group)were also collected.Bacterial colonies were counted and identified.Results A total of 714 air specimens were collected from 238 bed units of 45 hemodialysis units before and during bed-making.The average bacterial colony count during bed-making was higher than that before bed-making([2.72±3.43]CFU/plate vs[0.69±1.50]CFU/plate,P＜0.05).The qualified rate of microbial colony count before bed-making was higher than that during bed-making(96.64％vs 64.71％,P＜0.05).A total of 450 environmental ob-ject surface specimens from 90 bed units of 45 hemodialysis units were collected before and after terminal disinfec-tion.The average bacterial colony count before terminal disinfection was higher than that after terminal disinfection([8.18±20.6]CFU/cm2 vs[1.49±3.44]CFU/cm2.P＜0.05).The qualified rate of microbial colony count after terminal disinfection was higher than that before terminal disinfection(98.22％vs 92.44％,P＜0.05).The micro-organisms in the air and environment were mainly coagulase negative Staphylococcus.Conclusion Bed-making has a certain impact on the air microorganisms around the bed units,and terminal disinfection can reduce the bacterial co-lony count of the environment.It is necessary to pay attention to the cleaning and disinfection of the environment for medical treatment,and carry out bed-making manipulation under clear condition to minimize the risk of infection.

Objective To establish the HPLC analysis method for ketoconazole related substances,and to provide technical support for the improvement of the quality standard and the purity of ketoconazole.Methods Gradient elution conditions were optimized based on the chromatographic parameters outlined in the 2024"British Pharmacopoeia"for ketoconazole cream.A C18 column(4.6 mm×150 mm,3 μm)was used to facilitate the elution process using a gradient of acetonitrile and acetate buffer,and detection performed at a wavelength of 230 nm.Results The known impurities and potentially genotoxic impurities in the material drugs of ketoconazole can be more effectively separated using the established methods,which are both robust and highly sensitive.The content of the two potentially geno toxic impurities,six known impurities and unknown impurities in the 21 batches of ketoconazole sourced from five raw material pharmaceutical companies is below the specified limit requirements.Conclusion This method contributes to improving the quality of ketoconazole ingredients,ensuring the safety of ketoconazole preparations,and better supporting the regulatory supervision.

Objective To understand the impact of bed-making manipulation on the air surrounding bed units in hemodialysis room,evaluate the effectiveness of routine terminal disinfection,and provide scientific basis for optimi-zing infection control measures.Methods Air specimens(pre-bed-making group)and environmental object surface specimens(pre-terminal disinfection group)around bed units were collected when hemodialysis was about to be fi-nished.Air specimens after bed-making(bed-making group)and environmental object surface specimens after ter-minal disinfection(terminal disinfection group)were also collected.Bacterial colonies were counted and identified.Results A total of 714 air specimens were collected from 238 bed units of 45 hemodialysis units before and during bed-making.The average bacterial colony count during bed-making was higher than that before bed-making([2.72±3.43]CFU/plate vs[0.69±1.50]CFU/plate,P＜0.05).The qualified rate of microbial colony count before bed-making was higher than that during bed-making(96.64％vs 64.71％,P＜0.05).A total of 450 environmental ob-ject surface specimens from 90 bed units of 45 hemodialysis units were collected before and after terminal disinfec-tion.The average bacterial colony count before terminal disinfection was higher than that after terminal disinfection([8.18±20.6]CFU/cm2 vs[1.49±3.44]CFU/cm2.P＜0.05).The qualified rate of microbial colony count after terminal disinfection was higher than that before terminal disinfection(98.22％vs 92.44％,P＜0.05).The micro-organisms in the air and environment were mainly coagulase negative Staphylococcus.Conclusion Bed-making has a certain impact on the air microorganisms around the bed units,and terminal disinfection can reduce the bacterial co-lony count of the environment.It is necessary to pay attention to the cleaning and disinfection of the environment for medical treatment,and carry out bed-making manipulation under clear condition to minimize the risk of infection.

Objective:To comprehensively evaluate the medical service capacity of 50 first batch county medical sub-centers in Guizhou Province,it provides the basis and references for further research on the construction of county medical sub-centers in Guizhou province and improvement of the medical service capacity of township health centers(community health service centers)in Guizhou Province.Methods:Through TOPSIS method,RSR method and the fuzzy combination method,the medical service capacity of the primary medical institutions in the county medical sub-center was evaluated.Results:Among the first batch of 50 county-level secondary medical centers,the top three in terms of medical service capabilities were G18,G6,and G36,while the last three were G27,G15,and G22.Conclusion:There were significant differences in the medical and health service capacity among the 50 sub-centers.It is suggested to continue to increase the support for sub-centers,formulate relevant policies according to local conditions and time conditions,and improve the medical service capacity of sub-centers.

Objective To explore the relationship between the head injury criterion(HIC)values in anterior-posterior(AP)collisions and lateral-medial(LM)collisions.Methods A total of 102 male SD rats were randomly divided into a control group of 0 m(6 rats),4 AP groups(12 rats/group)and 4 LM groups(12 rats/group).After adaptive training,the classical Marmarou model was used to execute the brain AP and LM collisions under a series of different height impacts,and the HIC values were calculated.The experimental group data of the walk-pole test and grip strength test were collected at 24 hours before and after injury,and the data of the proportion of hemorrhage in the corpus callosum and pyramidal tracts were collected at 24 hours after injury.Results As the collision heights increased in both AP and LM groups,there were positive correlations with changes in WP test time and peak GS,and corresponding increases in the proportion of hemorrhage in the cc and py.According to the mathematical relationships between the comprehensive injury degrees and HIC values,it was found that at the same injury degree,LM-HIC value was less than AP-HIC value.A mathematical relationship between AP-HIC and LM-HIC was fitted based on the comprehensive injury degrees.At the same HIC,LM group experienced more severe injuries,and AP group was more tolerant to head collision.Conclusion The injury severity in LM group is greater than that of AP group at the same HIC.Preliminary results show there is a linear mathematical relationship between AP-HIC and LM-HIC.These results can be expected to expand the application scope of HIC and achieve an accurate assessment of the LM collision severity.

AIM:To explore the potential mecha-nism of arecoline in promoting oral submucous fi-brosis based on key factors of phosphatidylinositol 3-kinase(PI3K)/protein kinase B(Akt)/mammalian target of rapamycin(mTOR)pathway.METHODS:SD rats were randomly divided into arecoline low-dose group,arecoline medium-dose group,and are-coline high-dose group(5,10,and 15 mg/mL).The oral buccal mucosa was injected with the corre-sponding concentration of arecoline(ANE)solution to induce the establishment of oral submucous fi-brosis(OSF)models,with 8 rats in each group.An-other 8 unmodeled rats were selected as the blank group,and the changes in mouth opening of the rats were detected after 8 weeks of grouping and intervention.HE and Masson staining were used to observe the pathological changes of oral buccal mucosa,measure the length of epithelial staple process and calculate collagen volume fraction.Western blot and qRT-PCR were used to detect the expression of collagen-Ⅰ(COL-Ⅰ),E-cadherin,fibro-nectin(FN)and PI3K/Akt/mTOR signaling pathway-related proteins and mRNA in rat oral buccal muco-sa.The levels of tumor necrosis factor(TNF)-α,in-terleukin(IL)-1β and transforming growth factor(TGF)-β1 in rat serum were detected by ELISA.Hu-man immortalized keratinocytes(HaCaT cell line)were cultured in vitro,and the effects of different concentrations of arecoline,PI3K activator,and PI3K inhibitor on the survival rate of HaCaT cells were investigated by CCK-8 method.According to the results of CCK-8,the concentration of arecoline 75 μg/mL,the concentration of PI3K activator 10μmol/L,and the concentration of PI3K inhibitor 2μmol/L were selected as the subsequent experi-mental concentrations.The cells were set as blank group,arecoline group,PI3K activator group,PI3K inhibitor group,and arecoline+PI3K inhibitor group.The mRNA expression levels of COL-Ⅰ,E-cad-herin,FN,PI3K,Akt,and mTOR in each group of cells were detected by qRT-PCR.The levels of TNF-α,IL-1β and TGF-β1 in each group of cells were de-tected by ELISA.RESULTS:Compared with the blank group,the arecoline low-dose group,the are-coline medium-dose group,and the arecoline high-dose group significantly reduced the mouth open-ing,significantly shortened the length of the epi-thelial staple process,significantly increased the collagen volume fraction,inflammatory cell infiltra-tion,and severe pathological damage.The protein expression levels of COL-Ⅰ,FN,p-PI3K,p-Akt,and p-mTOR were up-regulated,and the protein expres-sion levels of E-cadherin were down-regulated.The mRNA expressions of COL-Ⅰ,FN,PI3K,Akt,and mTOR were significantly increased.The mRNA ex-pression of E-cadherin was significantly reduced,and the levels of TNF-α,IL-1β,and TGF-β1 were sig-nificantly increased(all P＜0.05 or P＜0.01).Com-pared with the blank group,the mRNA expression levels of COL-Ⅰ,FN,PI3K,Akt,and mTOR in the cells of the arecoline group and the PI3K activator group were up-regulated,and the mRNA expression lev-els of E-cadherin were down-regulated.Compared with the blank group,the mRNA expression levels of COL-Ⅰ,FN,PI3K,Akt,and mTOR in the cells of the PI3K inhibitor group were down-regulated,and the mRNA expression levels of E-cadherin were up-regulated.Compared with the PI3K inhibitor group,the mRNA expression levels of COL-Ⅰ,FN,PI3K,Akt,and mTOR in the cells of the arecoline+PI3K inhibi-tor group were up-regulated,the mRNA expression levels of E-cadherin were down-regulated,and the levels of TNF-α,IL-1β,and TGF-β1 were significant-ly increased(all P＜0.05 or P＜0.01).CONCLUSION:Arecoline can significantly promote oral submucous fibrosis,which may play a pro-fibrotic role by up-regulating the PI3K/Akt/mTOR signaling pathway.