ObjectiveTo explore the clinical characteristics and risk factors for 30-day mortality in hospitalized patients with bloodstream infections (BSI) caused by carbapenem-resistant Klebsiella pneumoniae (CRKP). MethodsData were obtained retrospectively from the electronic medical records of inpatients at a tertiary A-grade hospital in Shanghai from January 2016 to December 2023. The collected variables included age, gender, department, surgical treatment, empirical antibiotic therapy, Pitt Bacteremia score (PBS), Charlson comorbidity index (CCI), INCREMENT-CPE score (ICS), length of hospital stay, the time from CRKP-BSI to discharge and, etc. The follow-up period ended upon discharge, with the follow-up outcomes defined as in-hospital mortality or discharge. The endpoint was defined as death within 30 days (including day 30) caused by CRKP-BSI or infection-related complications. Patients who survived within 30 days after CRKP-BSI were classified into the survival group, while those who died within 30 days were classified into the death group. Independent risk factors for 30-day mortality in patients with CRKP-BSI were analyzed using univariate and multivariate Cox regression analysis. ResultsA total of 71 hospitalized patients with CRKP-BSI, comprising 51 males and 20 females, with an average age of (65.12±18.25) years, were included during the study period. The M (P₂₅, P₇₅) of hospital stay were 37.00 (24.00, 56.00) days, and M (P₂₅, P₇₅) of the duration from CRKP-BSI to discharge or death were 18.00 (7.00, 35.00) days. There were 20 deaths (28.17%) in the death group and 51 survivors (71.83%) in the survival group. The results of multivariate Cox regression analysis showed that the ICS as an independent risk factor for 30-day mortality in CRKP-BSI patients (HR=1.379, 95%CI: 1.137‒1.671, P=0.001). Each 1-point increase in the ICS was associated with a 37.9% increase in the risk of mortality. ConclusionThe ICS is found to be a risk factor for 30-day mortality in patients with CRKP-BSI, which may facilitate the prediction for the risk of 30-day mortality and thereby support clinical decision-making for patients with CRKP-BSI.

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 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 difference in terahertz signal characteristics between rat skin scar and normal skin using terahertz time-domain spectroscopy technology,thereby providing a novel non-invasive detection technique for the pathological examination of skin scars.Methods A rat model of whole-layer skin defect was prepared,and a reflectance terahertz time-domain spectroscopy system was used to obtain the terahertz signal maps of normal skin and scarred area.Results The terahertz signals of normal skin showed two obvious reflection time-domain signal peaks,and the characteristics of the reflection peaks at different reflection points were relatively regular.The terahertz signals of skin scar also had two obvious reflection time-domain signal peaks,but the highest peak was lower than that of normal skin.In addition,principal component analysis revealed that skin scar signals and normal skin signals were clustered together separately.The terahertz signal at different sites differed significantly(P<0.05).Conclusion Terahertz time-domain spectroscopy technology can be applied to the non-invasive detection of skin scarring,exhibiting a good application prospect in biomedicine.

Objective:To describe the current status and changes of multisymptom burden during the post-transplant hematopoietic reconstruction period in children with hematopoietic stem cell transplantation, and to provide reference for the precise management of symptoms in post-transplantation children.Methods:Children aged 7-18 years who underwent hematopoietic stem cell transplantation in Shanghai Children′s Medical Centre, Shanghai Jiao Tong University School of Medicine from September 2022 to October 2023 were selected by convenience sampling method. The Pediatric Patient Reported Outcomes version of Common Terminology Criteria for Adverse Events was used to assess multiple symptoms and burden during the reconstruction period on days 0, 7, 14, and 21 after transplantation.Results:Finally, 90 children who underwent hematopoietic stem cell transplantation were investigated, including 61 males and 29 females, aged (9.98 ± 2.96) years old. On days 0, 7, 14, and 21 after transplantation, the number of symptoms, severity of symptoms, degree of symptom interference were 20.00 (14.00), 18.00 (14.50), and 10.00 (9.75), with scores of 0.18 (0.30), 0.14 (0.29), 0.08 (0.13), 0.00 (0.08), and 0.27 (0.42), 0.19 (0.30), 0.09 (0.16), 0.03 (0.11), respectively. The overall differences were statistically significant ( Z=101.69, 93.70, 96.65, all P<0.01). The symptom burden in children showed four different trajectories including higher symptom burden in the early stages and lower in the later stages, consistently high burden, high symptom burden followed by low symptom burden, and consistently low burden. Conclusions:Children after hematopoietic stem cell transplantation are plagued by multiple symptoms during hematopoietic reconstruction, and with the treatment and time, different symptoms show different trajectories of change. Healthcare professionals should accurately assess the symptomatic changes of children after transplantation and provide targeted interventions to reduce the symptomatic burden and promote the recovery of children.

Objective:To investigate levels of endothelin-1(ET-1)and Apclin in patients with hypertrophic car-diomyopathy(HCM)and diagnostic value of their combination with ECG for HCM,and their association with prognosis.Methods:A total of 150 HCM patients admitted in the Second Affiliated Hospital of Xi'an Medical Uni-versity between June 2020 and June 2022 were selected as observation group.According to death during follow-up,the observation group was divided into survival group(n=64)and death group(n=86),and another 100 healthy volunteers who underwent physical examination in our hospital simultaneously were selected as control group.ET-1,Apelin and ECG indexes were compared between above-mentioned groups.Diagnostic value of ET-1,Apelin and ECG combined detection for HCM was analyzed by receiver operating characteristic(ROC)curve.Multivariate Logistic regression was used to analyze influencing factors of death within 6-month follow-up in HCM patients,and nomogram model was established.Results:Compared with participants in control group,those in the observa-tion group had significant higher ET-1[(0.64±0.15)pmol/L vs.(0.39±0.07)pmol/L],QRS wave group(∑QRS)[(23.60±3.96)mm vs.(14.02±1.78)mm],Cornell voltage index(SV3+RaVL)[(2.12±0.40)mV vs.(1.05±0.20)mV]and S-wave on V1 lead+R-wave on V5 lead(SV1+RV5)[(3.88±0.73)mV vs.(2.24±0.34)mV],and significant lower Apelin[(1.10±0.25)pg/ml vs.(1.58±0.17)pg/ml]level(P＜0.001 all).ROC curve indicated that the area under the curve(AUC)of combined detection of above five indexes diagno-sing HCM was 0.933(95％CI 0.895～0.961),significantly higher than any single detection(Z=3.681～6.428,P＜0.001 all),the H-L goodness of fit test showed P=0.056,suggesting that the model was well accepted,and DCA showed that ET-1 and Apelin combined ECG detection model had good clinical application value in HCM.Multivariate Logistic regression indicated that ET-1,∑QRS,SV3+RaV and SV1+RV5 were independent risk factors for death within 6-month in HCM patients(OR=2.617～3.600,P＜0.001 all),and Apelin was its inde-pendent protective factor(OR=0.271,P＜0.001).The nomogram model of HCM patients dying within 6 months was 4.627+0.452 × ET-1+0.536 × Apelin+0.575 × ∑QRS+0.541 × SV3+RaVL+0.352 × SV1+RV5.Conclusion:Serum ET-1 and Apelin levels significantly change in HCM patients,and the combination of ECG detection and both indexes have good performance diagnosing HCM and are independent influential factors for the death of HCM patients within 6 months.

Human epidermal growth factor receptor 2 (HER2) is a key therapeutic target for breast cancer. With the wide application of anti-HER2 and HER2 antibody-drug conjugates such as trastuzumab, pertuzumab, trastuzumab emtansine, and trastuzumab deruxtecan, the survival of patients with advanced HER2-positive breast cancers have been significantly improved. However, the subsequent drug-induced interstitial lung disease (DILD) has gradually become an important complication affecting the therapeutic effect and safety. However, the clinical understanding of interstitial lung disease (ILD) caused by this type of drugs is still insufficient, the management lacks unified standards, and the molecular mechanism has not been fully clarified. This study, through two clinical cases of severe DILD, explores the pathogenesis, treatment strategies, risk factors and follow-up monitoring requirements of ILD caused by HER2-targeted drugs, providing a scientific basis for optimizing the clinical diagnosis and treatment plan.

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.