OBJECTIVE: To explore the functional roles and underlying mechanisms of neferine in the context of angiotensin II (Ang II)-induced hypertension and vascular dysfunction. METHODS: Male mice were infused with Ang II to induce hypertension and randomly divided into treatment groups receiving neferine or a control vehicle based on baseline blood pressure using a random number table method. The hypertensive mouse model was constructed by infusing Ang II via a micro-osmotic pump (500 ng/kg per minute), and neferine (0.1, 1, or 10 mg/kg), valsartan (10 mg/kg), or double distilled water was administered intragastrically once daily for 6 weeks. A non-invasive blood pressure system, ultrasound, and hematoxylin and eosin staining were performed to assess blood pressure and vascular changes. RNA sequencing and network pharmacology were employed to identify differentially expressed transcripts (DETs) and pathways. Vascular ring tension assay was used to test vascular function. A7R5 cells were incubated with neferine for 24 h and then treated with Ang II to record the real-time Ca²⁺ concentration by confocal microscope. Immunohistochemistry (IHC) and Western blot were used to evaluate vasorelaxation, calcium, and the extracellular signal-regulated kinase (ERK)1/2 pathway. RESULTS: Neferine treatment effectively mitigated the elevation in blood pressure, pulse wave velocity, aortic thickening in the abdominal aorta of Ang II-infused mice (P<0.05). RNA sequencing and network pharmacology analysis identified 355 DETs that were significantly reversed by neferine treatment, along with 25 potential target genes, which were further enriched in multiple pathways and biological processes, such as ERK1 and ERK2 cascade regulation, calcium pathway, and vascular smooth muscle contraction. Further investigation revealed that neferine treatment enhanced vasorelaxation and reduced Ca²⁺-dependent contraction of abdominal aortic rings, independent of endothelium function (P<0.05). The underlying mechanisms were mediated, at least in part, via suppression of receptor-operated channels, store-operated channels, or voltage-operated calcium channels. Neferine pre-treatment demonstrated a reduction in intracellular Ca²⁺ release in Ang II stimulated A7R5 cells. IHC staining and Western blot confirmed that neferine treatment effectively attenuated the upregulation of p-ERK1/2 both in vivo and in vitro, which was similar with treatment of ERK1/2 inhibitor PD98059 (P<0.05). CONCLUSIONS Neferine remarkably alleviates Ang II-induced elevation of blood pressure, vascular dysfunction, and pathological changes in the abdominal aorta. This beneficial effect is mediated by the modulation of multiple pathways, including calcium and ERK1/2 pathways.
Animals ; Angiotensin II ; Male ; Benzylisoquinolines/therapeutic use* ; Network Pharmacology ; Blood Pressure/drug effects* ; Sequence Analysis, RNA ; Mice ; Hypertension/chemically induced* ; Mice, Inbred C57BL ; Calcium/metabolism*

Objective:To report the nationwide surveillance results of pathogenic profiles and antimicrobial resistance patterns of Gram-positive bloodstream infections in China in 2023.Methods:The clinical isolates of Gram-posttive bacteria from blood cultures were collected in member hospitals of National Bloodstream Infection Bacterial Resistant Investigation Collaborative System（BRICS）during January to December 2023. Antimicrobial susceptibility testing was performed using the dilution method recommended by the Clinical and Laboratory Standards Institute（CLSI）. Statistical analyses were conducted using WHONET 5.6 and SPSS 25.0 software.Results:A total of 4 385 Gram-positive bacterial isolates were obtained from 60 participating center. The top five pathogens were Staphylococcus aureus（ n=1 544，35.2%），coagulase-negative Staphylococci（ n=1 441，32.9%）， Enterococcus faecium（ n=574，13.1%）， Enterococcus faecalis（ n=385，8.8%），and α-hemolytic Streptococci（ n=187，4.3%）. The prevalence of methicillin-resistant Staphylococcus aureus（MRSA）and methicillin-resistant coagulase-negative Staphylococci（MRCNS）was 26.2%（405/1 544）and 69.8%（1 006/1 441），respectively. Notably，all Staphylococci remained susceptible to glycopeptide or daptomycin. Staphylococcus aureus demonstrated excellent susceptibility（>97.0%）to cephalobiol，rifampicin，trimethoprim-sulfamethoxazole，linezolid，minocycline，tigecycline，and eravacycline. No Enterococcus exhibiting resistance to linezolid were detected. Glycopeptide resistance was uncommon but more frequent in Enterococcus faecium（resistance to vancomycin and teicoplanin：both 1.7%）compared to Enterococcus faecalis（both 0.3%）. The detection rates of MRSA and MRCNS exhibited significant regional variations across the country（ χ2=17.674 and 148.650，respectively，both P<0.001）. No vancomycin-resistant Enterococci were detected in central China. Institutional comparison demonstrated higher prevalence of MRSA（ χ2=14.111， P<0.001）and MRCNS（ χ2=4.828， P=0.028）in provincial hospitals than that in municipal hospitals. Socioeconomic analysis identified elevated detection rates of both MRSA（ χ2=18.986， P<0.001）and MRCNS（ χ2=4.477， P=0.034）in less developed regions（per capita GDP

Objective:To report the results of bacterial resistant investigation collaborative system（BRICS）on the distribution and antimicrobial resistance profile of clinical Gram-negative bacteria isolates from bloodstream infections in China in 2023，and provide reference for clinical tretment of bloodstream infections and prevention and control of bacterial resistance.Methods:The clinical isolates of Gram-negative bacteria from blood cultures in member hospitals of BRICS were collected during January 2023 to December 2023. Antibiotic susceptibility tests were conducted by agar dilution or broth dilution methods recommended by Clinical and Laboratory Standards Institute（CLSI）. WHONET 5.6 and SPSS 25.0 were used to analyze the data.Results:During the study period，11 492 strains of Gram-negative bacteria were collected from 60 hospitals，of which 10 098（87.9%）were Enterobacterales and 1 394（12.1%）were non-fermentative bacteria. The top 5 bacterial species were Escherichia coli（50.0%）， Klebsiella pneumoniae（26.1%）， Pseudomonas aeruginosa（5.1%）， Acinetobacter baumannii complex（5.0%）and Enterobacter cloacae complex（4.1%）. The ESBL-producing rates in Escherichia coli， Klebsiella pneumoniae and Proteus mirablilis were 46.8%（2 685/5 741），18.3%（549/2 999）and 44.0%（77/175），respectively. The prevalence of carbapenem-resistant Escherichia coli（CREC）and carbapenem-resistant Klebsiella pneumoniae（CRKP）were 1.3%（76/5 741）and 15.0%（450/2 999）；32.9%（25/76）and 78.0%（351/450）of CREC and CRKP were sensitive to ceftazidime/avibactam combination，respectively. 94.7%（72/76）and 90.2%（406/450）of CREC and CRKP were sensitive to aztreonam/avibactam combination. Furthermore，57.9%（44/76）and 79.1%（356/450）were sensitive to imipenem/relebactam combination. The prevalence of carbapenem-resistant Acinetobacter baumannii（CRAB）complex was 64.6%（370/573），while more than 80.0% of CRAB complex was sensitive to tigecycline，eravacycline and polymyxin B. The prevalence of carbapenem-resistant Pseudomonas aeruginosa（CRPA）was 17.0%（99/581）. There were differences in the composition ratio of Gram-negative bacteria in bloodstream infections and the prevalence of important Gram-negative bacteria resistance among different regions in China，with statistically significant differences in the prevalence of CREC，CRKP，CRPA and CRAB complex（ χ2=10.6，28.6，10.8 and 19.3， P<0.05）. The prevalence of ESBL-producing Escherichia coli， CREC，CRAB complex and CRKP were higher in provincial hospitals than those in municipal hospitals（ χ2=12.5，9.8，12.7 and 57.8，all P<0.01）. Conclusions:Gram-negative bacteria are the main pathogens causing bloodstream infections in China，and Escherichia coli is ranked in the top，while the trend of Klebsiella pneumoniae increases continuously with time. CRKP infection shows a slow upward trend，CREC infecton maintains a low prevalence level，and CRAB complex infection continues to exhibit a high prevalence rate. The composition and resistance patterns of pathogens causing bloodstream infections vary to some extent across different regions and levels of hospitals in China.

BACKGROUND:Neuroinflammation is a major cause of exacerbation after spinal cord injury.In recent years,pyroptosis has received much attention due to its remarkable pro-inflammatory features.Some of these natural products can significantly inhibit the inflammatory response and improve the damaged nerve function by regulating the level of pyroptosis after spinal cord injury,which provides a new therapeutic idea for spinal cord injury.OBJECTIVE:To summarize the mechanism of action of natural products in regulating pyroptosis for the treatment of spinal cord injury,with a view to providing lessons and references for future research on the treatment of spinal cord injury.METHODS:The search terms"spinal cord injury,pyroptosis,inflammasome,natural products,natural compounds,traditional Chinese medicine"in Chinese and English were used to search for relevant literature since the establishment of the database up to September 2024 in the databases of PubMed,Web of Science,WanFang,and CNKI.According to the inclusion and exclusion criteria,75 relevant articles were finally obtained.RESULTS AND CONCLUSION:(1)Pyroptosis is an important pro-inflammatory pathway in spinal cord injury,and controlling pyroptosis is an effective way to improve damaged nerve function.(2)Some natural products can regulate pyroptosis via the NLRP3/Caspase-1 classical pyroptosis pathway,the NF-κB-related pathway,other upstream pathways such as Nrf2/HO-1,and autophagy,thereby affecting the level of tissue inflammation and accelerating neurological recovery after spinal cord injury.(3)The anti-pyroptosis effects of these natural products are mostly dependent on the NLRP3 classical pyroptosis pathway,and there is a lack of studies on other pyroptosis pathways.(4)There are still many problems in this field,such as the fact that these natural products are not currently supported by evidence from appropriate clinical studies.(5)The natural product has great potential in regulating pyroptosis and is expected to be a powerful weapon in the treatment of spinal cord injury.

Objective To compare the effect of moderate-intensity continuous training(MICT)and high-intensity interval training(HIIT)on gait and balance for stroke patients.Methods From December,2023 to December,2024,96 patients with post-stroke gait and balance dysfunction were se-lected from the First Affiliated Hospital of Bengbu Medical University,and randomly divided into control group(n=32),MICT group(n=32)and HIIT group(n=32).The control group received routine comprehensive reha-bilitation therapy,while MICT and HIIT groups received additional respective training,for four weeks.They were measured with symmetry indexes(SI)of mean pressure and footprint area during eyes-open and eyes-closed condition,as well as anterior-posterior and medial-lateral displacement of the center of mass,before and after treatment;while they were assessed with Berg Balance Scale(BBS),distance of 6-minute walk test(6MWT),time of Timed Up&Go test(TUGT)and 10-meter walk test(10MWT),and Fugl-Meyer Assessment-Lower Extremities(FMA-LE).Results The main effects of time(F>351.683,P<0.001)and groups(F>4.945,P<0.05),and the interaction effects(F>16.919,P<0.001)were significant for BBS scores,distance of 6MWT,time of TUGT and 10MWT,and FMA-LE scores;and all the indicators were better in MICT group and HIIT group than in the control group(P<0.05)after treatment,and they were better in HIIT group than in MICT group(P<0.05)except BBS score.Un-der eyes-open condition,the main effects of time(F>64.684,P<0.001)and groups(F>9.472,P<0.001),and the interaction effects(F>10.562,P<0.001)were significant for SI of mean pressure and footprint area,and an-terior-posterior and medial-lateral displacement of the center of mass;and all the indicators were better in MICT group and HIIT group than in the control group(P<0.001)after treatment,and they were better in HIIT group than in MICT group(P<0.05).Under eyes-closed condition,the main effects of time(F>107.730,P<0.001)and groups(F>4.275,P<0.05),and the interaction effects(F>7.985,P<0.05)were significant for SI of mean pressure and footprint area,and anterior-posterior and medial-lateral displacement of the center of mass;and SI of mean pressure was better in HIIT group than in MICT group(P<0.05),the other indicators were better in MICT group and HIIT group than in the control group(P<0.001)after treatment.Conclusion Both HIIT and MICT can improve gait and balance for stroke patients,and HIIT is more effective on gait and static balance with eyes open,but similar on static balance with eyes closed.

Objective To analyze the effect of diltiazem on blood concentration of tacrolimus(TAC)retrospectively,and to provide reference for individual administration of tacrolimus in patients with nephrotic syndrome(NS).Methods The patients with NS who were treated in the outpatient/inpatient department of our hospital from January 2018 to December 2022 were collected,and the general information,combined drug use,blood drug concentration and other information of the patients were recorded.The patients were divided into two groups according to whether diltiazem was used or not:TAC group alone and TAC group combined with diltiazem.The effect of diltiazem on tacrolimus concentration was analyzed.Results A total of 45 patients with NS were included in this study,and 21 patients in the TAC group were treated with TAC alone.The mean blood concentration of TAC after medication was(5.77±2.87)ng·mL-1,which reached the effective therapeutic concentration range.The average blood concentration of TAC+Diltiazem group in the 24 patients was(2.90±1.29)ng·mL-1 before combined treatment,and increased to(5.74±2.46)ng·mL-1 after combined with diltiazem,with a growth rate of(127.34±119.57)％.The increase range was from 10％to 288％,and there was significant difference(P＜0.05).According to the observation within 6 months after the combination of the two drugs,the average blood concentration of TAC continued to increase,especially in the 5th month after the administration of TAC,and the concentration tended to be stable after 5 months.By compare with the effect of diltiazem dosage on the blood concentration of TAC,90 mg·d-1 and 180 mg·d-1 had little difference in improving the blood concentration of TAC.At the same time,the combination of the two drugs did not cause adverse reactions.Conclusion A daily dose of 90 mg of Diltiazem can significantly increase the TAC blood concentration in patients with NS who cannot reach the effective therapeutic concentration with conventional doses.It can reach the effective clinical therapeutic concentration without increasing the dose of tacrolimus.The combination of the two drugs were generally safe and effective.

Objective:Interpret the key differences between the China Health-care Security Diagnosis Related Groups(CHS-DRG)2.0 and CHS-DRG 1.1,and provide reference for optimizing management strategies in medical institutions.Methods:Text analysis was used to import the CHS-DRG 2.0 and 1.1 grouping scheme dictionary data into the SQL database in a structured table format using SQL Server 2014.The key differences between the two schemes in grouping structure,grouping rules,grouping results,and other aspects were identified.Results:CHS-DRG 2.0 version added 26 groups,deleted 3 groups,and refined 10 groups into 20 groups for 14 clinical specialties at the ADRG level compared to CHS-DRG 1.1.Some group codes,names,and grouping rules were adjusted;Adjusted some grouping conditions and grouping results at the DRG level.Conclusion:CHS-DRG 2.0 version has improved grouping efficiency compared to CHS-DRG 1.1,solved some clinical bottleneck problems,and standardized the role of clinical diagnosis in grouping from the perspective of resource consumption.However,it has not completely solved the grouping problems of multi disease co treatment,multi disease treatment,and combined surgery.The adjustment of DRG weights and rates,the follow-up of related supporting policy reforms,and the negative effects of DRG will still pose challenges for medical institutions.

Objective:Interpret the key differences between the China Health-care Security Diagnosis Related Groups(CHS-DRG)2.0 and CHS-DRG 1.1,and provide reference for optimizing management strategies in medical institutions.Methods:Text analysis was used to import the CHS-DRG 2.0 and 1.1 grouping scheme dictionary data into the SQL database in a structured table format using SQL Server 2014.The key differences between the two schemes in grouping structure,grouping rules,grouping results,and other aspects were identified.Results:CHS-DRG 2.0 version added 26 groups,deleted 3 groups,and refined 10 groups into 20 groups for 14 clinical specialties at the ADRG level compared to CHS-DRG 1.1.Some group codes,names,and grouping rules were adjusted;Adjusted some grouping conditions and grouping results at the DRG level.Conclusion:CHS-DRG 2.0 version has improved grouping efficiency compared to CHS-DRG 1.1,solved some clinical bottleneck problems,and standardized the role of clinical diagnosis in grouping from the perspective of resource consumption.However,it has not completely solved the grouping problems of multi disease co treatment,multi disease treatment,and combined surgery.The adjustment of DRG weights and rates,the follow-up of related supporting policy reforms,and the negative effects of DRG will still pose challenges for medical institutions.

BACKGROUND:Neuroinflammation is a major cause of exacerbation after spinal cord injury.In recent years,pyroptosis has received much attention due to its remarkable pro-inflammatory features.Some of these natural products can significantly inhibit the inflammatory response and improve the damaged nerve function by regulating the level of pyroptosis after spinal cord injury,which provides a new therapeutic idea for spinal cord injury.OBJECTIVE:To summarize the mechanism of action of natural products in regulating pyroptosis for the treatment of spinal cord injury,with a view to providing lessons and references for future research on the treatment of spinal cord injury.METHODS:The search terms"spinal cord injury,pyroptosis,inflammasome,natural products,natural compounds,traditional Chinese medicine"in Chinese and English were used to search for relevant literature since the establishment of the database up to September 2024 in the databases of PubMed,Web of Science,WanFang,and CNKI.According to the inclusion and exclusion criteria,75 relevant articles were finally obtained.RESULTS AND CONCLUSION:(1)Pyroptosis is an important pro-inflammatory pathway in spinal cord injury,and controlling pyroptosis is an effective way to improve damaged nerve function.(2)Some natural products can regulate pyroptosis via the NLRP3/Caspase-1 classical pyroptosis pathway,the NF-κB-related pathway,other upstream pathways such as Nrf2/HO-1,and autophagy,thereby affecting the level of tissue inflammation and accelerating neurological recovery after spinal cord injury.(3)The anti-pyroptosis effects of these natural products are mostly dependent on the NLRP3 classical pyroptosis pathway,and there is a lack of studies on other pyroptosis pathways.(4)There are still many problems in this field,such as the fact that these natural products are not currently supported by evidence from appropriate clinical studies.(5)The natural product has great potential in regulating pyroptosis and is expected to be a powerful weapon in the treatment of spinal cord injury.

Objective To compare the effect of moderate-intensity continuous training(MICT)and high-intensity interval training(HIIT)on gait and balance for stroke patients.Methods From December,2023 to December,2024,96 patients with post-stroke gait and balance dysfunction were se-lected from the First Affiliated Hospital of Bengbu Medical University,and randomly divided into control group(n=32),MICT group(n=32)and HIIT group(n=32).The control group received routine comprehensive reha-bilitation therapy,while MICT and HIIT groups received additional respective training,for four weeks.They were measured with symmetry indexes(SI)of mean pressure and footprint area during eyes-open and eyes-closed condition,as well as anterior-posterior and medial-lateral displacement of the center of mass,before and after treatment;while they were assessed with Berg Balance Scale(BBS),distance of 6-minute walk test(6MWT),time of Timed Up&Go test(TUGT)and 10-meter walk test(10MWT),and Fugl-Meyer Assessment-Lower Extremities(FMA-LE).Results The main effects of time(F>351.683,P<0.001)and groups(F>4.945,P<0.05),and the interaction effects(F>16.919,P<0.001)were significant for BBS scores,distance of 6MWT,time of TUGT and 10MWT,and FMA-LE scores;and all the indicators were better in MICT group and HIIT group than in the control group(P<0.05)after treatment,and they were better in HIIT group than in MICT group(P<0.05)except BBS score.Un-der eyes-open condition,the main effects of time(F>64.684,P<0.001)and groups(F>9.472,P<0.001),and the interaction effects(F>10.562,P<0.001)were significant for SI of mean pressure and footprint area,and an-terior-posterior and medial-lateral displacement of the center of mass;and all the indicators were better in MICT group and HIIT group than in the control group(P<0.001)after treatment,and they were better in HIIT group than in MICT group(P<0.05).Under eyes-closed condition,the main effects of time(F>107.730,P<0.001)and groups(F>4.275,P<0.05),and the interaction effects(F>7.985,P<0.05)were significant for SI of mean pressure and footprint area,and anterior-posterior and medial-lateral displacement of the center of mass;and SI of mean pressure was better in HIIT group than in MICT group(P<0.05),the other indicators were better in MICT group and HIIT group than in the control group(P<0.001)after treatment.Conclusion Both HIIT and MICT can improve gait and balance for stroke patients,and HIIT is more effective on gait and static balance with eyes open,but similar on static balance with eyes closed.