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 explore the diagnostic value of ultrasonography in ischiofemoral impinge-ment syndrome(IFI).Methods Fifty-six patients who underwent hip MRI with confirmed IFI diagnosis and completed ultrasonography examinations were enrolled as the IFI group,including 44 females and 12 males.Twenty healthy volunteers were concurrently recruited as the control group,consisting of 10 females and 10 males.The control group underwent ultrasonography examinations of bilateral hip joints,whiletheischialfemoralspace(IFS)andquadratusfemoristhickness(QFT)of both groups were measured and recorded.Then measurements were compared within(by laterality and gender)and between the two groups using independent-samples t-tests.Moreover,receiver operating characteristic adults,males exhibited significantly higher IFS and QFT values than females(P<0.05).Within the IFI group,males with affected hips had significantly higher IFS than females(P<0.05),while no sig-nificant differences were observed in QFT between different genders(P>0.05).Moreover,affected hips in the IFI group showed significantly narrower IFS and thicker QFT compared to both contralateral hips and the control group(P<0.001).In addition,the diagnostic cut-off values of IFS and QFT for ultrasound diagnosis of IFI were 22.93 mm and 16.48 mm,respectively.At these thresholds,the ar-eas under the curve(AUC)were 0.997 and 0.977,with sensitivities of 97.8%and 91.8%,and speci-ficities of 98.4%and 97.8%,respectively.Conclusion Ultrasound can serve as a reliable diagnostic technique for IFI,where narrowing of the IFS and thickening of the QFT should raise suspicion of this condition.

Objective To evaluate the clinical efficacy of modified Rhinoceros Dihuang decoction in the treatment of children with henoch-sch?nlein purpura(HSP)of the"bleeding due to blood-heat syndrome"pattern in traditional Chinese medicine(TCM).Methods A total of 72 pediatric patients diagnosed with HSP and admitted to Zhengzhou Hospital of Traditional Chinese Medicine from June 2021 to June 2023 were enrolled and divided into two groups(n=36 each):control group and observation group.The control group received conveational Western medical treatment,while the observation group received additional treatment with modified Rhinoceros Dihuang decoction based on conventional therapy.The decoction was composed of:Herba Agrimoniae,Radix Rehmanniae,Radix Arnebiae seu Lithospermi,Radix Rubiae,15 g each;Cornu Bubali,30 g,Rhizoma Imperatae,20 g;Cortex Moutan and Radix Paeoniae Rubra,10 g each.The herbs were decocted once daily,dosed according to age:100 mL for ages 3-6,150 mL for 7-11,and 200 mL for 12-14 years old,administered twice daily for 10 days.Outcome measures included clinical efficacy,symptom scores(distribution,color,and morphology of purpura),inflammatory markers[interleukins(IL-17,IL-9),tumor necrosis factor-α(TNF-α)],immune function indicators[T lymphocyte subsets(CD4+,CD8+,CD4+/CD8+)and immunoglobulins(IgA,IgM,IgG)],quality of life,and adverse events.Results After treatment,the symptom scores,inflammatory factors,CD8+,IgA,and IgM levels in the observation group were significantly lower than those in the control group[purpura distribution score:1.03±0.20 vs.1.85±0.27,purpura color score:0.95±0.18 vs.1.76±0.31,purpura morphology score:0.94±0.16 vs.1.76±0.28;IL-17(ng/L):19.84±2.31 vs.26.12±2.63,IL-9(ng/L):20.40±4.19 vs.34.16±6.31,TNF-α(ng/L):13.61±2.05 vs.22.17±2.13;CD8+:0.259±0.040 vs.0.423±0.040,IgA(g/L):1.26±0.24 vs.1.81±0.32,IgM(g/L):1.24±0.19 vs.1.54±0.26,all P<0.05],CD4+,CD4+/CD8+,and IgG levels,as well as the pediatric quality of life inventory 4.0(PedsQL4.0)score were significantly higher in the observation group than in the control group[CD4+:0.461±0.046 vs.0.423±0.040,CD4+/CD8+:1.780±0.330 vs.1.450±0.270,IgG(g/L):11.22±1.75 vs.9.41±1.84,PedsQL4.0 score:83.62±6.54 vs.75.54±12.32,all P<0.05].The total clinical efficacy rate in the observation group was significantly higher than that in the control group[94.44%(34/36)vs.72.22%(26/36),P<0.05].No significant adverse reactions were observed in either group.Conclusion Modified Rhinoceros Dihuang decoction is effective and safe in alleviating clinical symptoms,reducing inflammatory responses,regulating immune function,and improving quality of life in children with HSP of the bleeding due to blood-heat pattern.

Objective:To compare the dose-response effects of single-fraction ultra-high dose rate (FLASH) and conventional dose rate (CONV) whole abdominal irradiation (WAI) with X-rays on acute radiation-induced intestinal injury in mice, in order to identify optimal dose parameters and potential mechanisms.Methods:A total of 186 male C57BL/6J mice were randomly assigned to a non-irradiation group ( n=6), FLASH irradiation groups ( n=90), and CONV irradiation groups ( n=90). Acute radiation-induced intestinal injury models were established using single-fraction WAI with 11, 12, 13, 14, and 15 Gy X-rays (200 Gy/s for FLASH and 4 Gy/min for CONV). Changes in body weight, stool characteristics, and disease activity index (DAI) scores were assessed at 9 d post-irradiation. At 7 d post-irradiation at 11, 12, and 13 Gy, the intestines were collected for macroscopic examination and length measurement. The small intestine was selected for HE staining and quantitative analysis of intestinal crypt number and mucosal epithelial thickness. The survival of mice was assessed at 15 d post-WAI across all dose groups. Results:After single-fraction WAI at 11, 12, and 13 Gy, the body weight was higher in the FLASH group than that in the CONV group ( t=10.17, 12.65, 10.16, P<0.05). The DAI scores for the FLASH group were 1.00±1.10, 3.17±0.75, and 2.83±1.17, respectively, which were lower than those of the CONV group (4.33±0.52, 7.00±0.00, 8.60±0.55; t=8.70, 11.71, 14.99, P<0.05). However, after WAI at 14 Gy and 15 Gy, there were no significant differences in body weight and DAI between the FLASH group and the CONV group ( P>0.05). At 7 d after single-fraction WAI at 11, 12, and 13 Gy, mice in the FLASH group exhibited less intestinal congestion, edema, and shortening compared with the CONV group. The difference between the FLASH and CONV groups were statistically significant in small intestine length at 11 and 13 Gy ( t=4.42, 3.78, P<0.05), and in colorectal length at 11 and 12 Gy ( t=3.97, 3.12, P<0.05). Small intestine HE staining revealed superior preservation of intestinal architecture in the FLASH group compared with the CONV group, characterized by longer villi, increased crypt numbers, thicker mucosal epithelium, and enhanced structural integrity. The differences in crypt number and mucosal epithelial thickness were statistically significant ( tcrypt=13.10, 23.80, 11.90; tmucosal=5.75, 2.64, 7.74; P<0.05). At 15 d post-irradiation, the survival rate in the 15 Gy FLASH group was higher than that in the CONV group (50% vs. 10%, χ2=5.39, P<0.05), with a median survival extension of 6 d ( HR=0.340, 95% CI: 0.115 4-0.999 9). No significant survival differences were observed between the FLASH group and the CONV group at 11, 12, 13, and 14 Gy ( P>0.05). Conclusions:FLASH irradiation significantly alleviated acute radiation-induced intestinal injury from medium single-fraction WAI with 11, 12, and 13 Gy X-rays compared with CONV irradiation, and showed potential to improve mouse survival after single-fraction WAI at 15 Gy. This effect is likely associated with the preservation of intestinal crypts and exhibits a dose-dependent relationship.

Objective To understand the epidemiological characteristics of road traffic accident injuries in Beijing can provide a theoretical basis for improving the pre-hospital emergency service capabilities and levels,and increasing patient survival rates while reducing disability,mortality rates.Methods A retrospective analysis was conducted on the medical records of 9207 patients who made pre-hospital emergency calls due to road traffic accident injuries at the Beijing Emergency Medical Center in 2023 to understand the patients' age,gender,injury time,injury location,injury degree and other characteristics.Results Traumatic diseases ranked first in the classification of emergency medical conditions in Beijing.Among them,road traffic accidents account for 37％.The ratio of male to female patients was 1.32∶1.The largest number of patients were aged 31-40,accounting for nearly 25％.The proportion of underage patients and those aged 71 and above was 12.16％.The differences in gender and age distribution were statistically significant,while the differences in gender distribution among different age groups were not statistically significant.Road traffic accident injuries occured most frequently in September and least in January.There were more cases in summer and autumn,and fewer in winter and spring.The most common injury sites in road traffic accidents were limbs/skin and head and neck,accounting for 81.06％.The patients with moderate severity of injuries were the most numerous,accounting for 85.29％.Conclusion To avoid road traffic accidents,prevention should be the priority.It is necessary to strengthen the joint governance of multiple departments and minimize the occurrence of road traffic accident from the source.Pre-hospital emergency care must focus on key populations and key seasons,strengthen professional skills training and resource allocation,ensure efficient and smooth connection between pre-hospital and in-hospital care.Popularize and publicize the importance of self-rescue and mutual rescue,promote first aid knowledge and skills training for the public,and create a social atmosphere where"rescue is right beside us".

BACKGROUND:Slow bone repair and poor bone formation quality are still problems during masquelet technique in the treatment of large segment bone defects.H-type vessels can induce osteogenesis,enhance the local angiogenesis and osteogenesis coupling,and promote bone repair.However,there are few reports on the role of H-type blood vessels in the bone induced membrane.OBJECTIVE:To construct a large segment bone defect model of SD rat tibia,observe the expression characteristics of H-type blood vessels in the bone induced membrane,then to identify the expression peak point of H-type blood vessels in the bone induced membrane and determine the optimal period of bone grafting.METHODS:Sixty SD rats were randomly divided into a control group(n=30)and a model group(n=30)by random number table method.The two groups were further divided into three subgroups at 4,6,and 8 weeks after bone cement implantation,with 10 rats in each group.A 4 mm bone defect model of the right tibia was constructed in both the control and the model groups.Polymethyl methacrylate bone cement was implanted in the model group to induce bone biomembrane formation,while bone cement was not implanted in the control group.At 4,6,and 8 weeks after bone cement implantation,6 rats were randomly selected at each time point.The bone induction membrane tissue was cut from the model group,and the non-bone soft tissue of the corresponding part was cut from the control group.The dynamic expressions of H-type blood vessels in the bone induced membrane were identified by immunofluorescence.The morphological changes of the bone induced membrane were observed by hematoxylin-eosin staining.The formation of blood vessels in the bone induced membrane was observed by angiography.The expression levels of osteoblast-specific transcription factor in the bone induced membrane were detected by immunohistochemistry.Four rats remained at each time point.In the model group,the bone induced membrane was cut open and the bone cement was removed and autologous coccyx was implanted.In the control group,autologous coccyx was implanted in the bone defect area.Micro-CT evaluation of the tibial defect was performed 8 weeks after bone grafting.RESULTS AND CONCLUSION:(1)Immunofluorescence staining showed that the expression of H-type vessels in the model group was most obvious 6 weeks after bone cement implantation,and the expression of H-type vessels in the model group at each time point after bone cement implantation was higher than that in the control group(P＜0.05).(2)Hematoxylin-eosin staining and angiography showed that the number and volume of new blood vessels at each time point after bone cement implantation in the model group were greater than those in the control group(P＜0.05).The order of the number and volume of new blood vessels in the model group was:8 weeks after bone cement implantation＞6 weeks after bone cement implantation＞4 weeks after bone cement implantation.(3)Immunohistochemical staining showed that the positive expression of osteoblast-specific transcription factors at each time point after bone cement implantation in the model group was higher than that in the control group(P＜0.05),and the positive expression of osteoblast-specific transcription factors in the model group was most obvious 6 weeks after bone cement implantation.(4)Micro-CT detection showed that the bone repair effect of the three subgroups in the model group was significantly better than that of the corresponding subgroups in the control group,and the bone repair effect of the subgroup in the model group 6 weeks after bone cement implantation was better than that of the subgroups 4 and 8 weeks after bone cement implantation.The results indicate that H-type blood vessels are dynamically expressed in the bone induced membrane and reached a peak 6 weeks after bone cement implantation.Good bone repair effects can be obtained by the bone induced membrane bone grafting 6 weeks after bone cement implantation.

Objective To investigate the effect of continuous theta burst stimulation-intermittent theta burst stimulation(cTBS-iT-BS)priming protocols with different time intervals on the plasticity of primary motor cortex(M1).Methods A total of 39 healthy young adults were recruited from Changzhou De'an Hospital from March to August,2024.Participants received cTBS-iTBS priming protocols with intervals of 5 minutes,10 minutes and 15 minutes using a randomized crossover design.Motor-evoked potential(MEP)amplitudes in M1 were recorded at baseline(before intervention)and 0 minute,10 minutes,20 minutes and 30 minutes after intervention.Results The main effects of stimulation protocol(F=19.761,P<0.001)and measurement time(F=10.224,P<0.001)were significant.At each time point after intervention,the MEP amplitude was significantly higher under the 10-minute interval than under the 5-minute and 15-minute intervals(t>3.010,P<0.05).Conclusion The 10-minute interval of cTBS-iTBS is more effective on M1 plasticity.

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*