Compared with conventional transdermal drug delivery systems, dissolving microneedles significantly enhance drug bioavailability by penetrating the stratum corneum barrier and achieving intradermal drug delivery. In order to improve the transdermal bioavailability of dexmedetomidine hydrochloride, in this study, a novel microneedle delivery system was developed for dexmedetomidine hydrochloride based on 3D printing combined with micro-molding. By systematically optimizing the microneedle geometrical parameters, array arrangement, and preparation process parameters, we determined the optimal ratio of drug-carrying matrix as 15% PVP (polyvinyl pyrrolidone) K90. The microneedles exhibited significant drug loading gradients, with mean content of (209.99±27.56) μg/patch, (405.31±30.31) μg/patch, and (621.61±34.43) μg/patch. They showed a regular pyramidal structure under SEM and handheld electron microscopy, and their mechanical strength allowed effective penetration into the stratum corneum. The surface contact angles were all < 90°, indicating excellent hydrophilicity. The microneedles dissolved completely within 10 min after skin insertion, achieving a cumulative release rate of 90% (Higuchi model, r=0.996) during 2 hours of in vitro transdermal permeation. The cytotoxicity test and hemolysis test verified good biocompatibility. Pharmacodynamic evaluation showed that the microneedle group demonstrated pain-relieving effect within 15 min, with the pain threshold at the time point of 60 min being 3 times that in the transdermal cream group. The microneedle system developed in this study not only offers an efficient drug delivery option for patients but also establishes an innovative platform for rapid percutaneous delivery of hydrophilic drugs, demonstrating significant potential in perioperative pain management.
Dexmedetomidine/pharmacokinetics* ; Printing, Three-Dimensional ; Needles ; Drug Delivery Systems/methods* ; Administration, Cutaneous ; Animals ; Microinjections/instrumentation* ; Skin Absorption ; Skin/metabolism*

Sodium-glucose cotransporter 2 inhibitors(SGLT2i)offer numerous benefits for patients with type 2 diabetes.These benefits include lowering blood pressure and glucose levels, regulating blood lipids, improving arteriosclerosis and endothelial function, reducing urinary protein and decreasing uric acid levels.Additionally, SGLT2i has shown positive outcomes in reducing the risk of kidney failure and cardiovascular adverse events in non-diabetic patients.Recent studies have also discovered that SGLT2i has anti-aging effects, which can potentially delay aging and improve age-related diseases.This article provides a comprehensive review of the potential mechanisms of SGLT2i in anti-aging, offering valuable insights for anti-aging strategies and the prevention of aging-related diseases.

This article provides an overview of metaverse medicine and summarizes the challenges faced by cancer patients, the applications and effects of metaverse medicine in this population, and the limitations and difficulties in clinical practice. These challenges include legal and ethical restrictions, as well as the need for further validation of clinical acceptability and feasibility. Researchers are encouraged to conduct extensive studies to refine the legal and regulatory frameworks, enhance the safety and adoption of metaverse medicine, and facilitate its localized development in cancer care.

Objective To detect and analyze the drug resistance characteristics,phylogenetic typing,and virulence gene distribution of Escherichia coli(E.coli)in blood culture.Methods The strains of E.coli isolated from consecutive non-repetitive blood cultures in our hospital from January 1,2019 to December 13,2020 were collected.The sensitivity of E.coli to 17 antibiotics was determined u-sing the micro-broth method.The bacterial genomic DNA was extracted using the boiling method,and then the arpA,chuA,yjaA,TspE4C2,ArpAgpE and trpAgpC genes were detected by PCR to determine the bacterial phylogroup.The virulence genes,including iutA,fimH,fyuA,kpsMT Ⅱ,cnf1,cvac,hlyA,traT,kpsMT Ⅲ,and PAI,were detected using the multiplex PCR.The differences in drug resistance and virulence gene distribution among different phylogroups were analyzed by the Chi-square test.Results 270 strains of E.coli in blood culture showed high resistance rates to ceftriaxone,compound sulfamethoxazole,ampicillin,ampicillin sulbactam,cefazolin,and ciprofloxacin,all exceeding 50.0％.They had good susceptibility to imipenem,ertapenem,amikacin,and piperacillin tazobactam,with resistance rates all below 5.0％.The most common phylogroups were types B2 and D,accounting for 38.0％and 16.2％,respectively,while type E and hidden branch type I were relatively rare,accounting for less than 1.0％.The virulence gene analysis revealed that the distribution rates of fimH and fyuA genes were the highest,both above 99.0％.The distribution rates of kpsMT Ⅲ,hlyA,and cvaC genes were relatively low,all below 20.0％.The Chi-square test showed that the distribution rates of viru-lence genes such as iutA,fimH,fyuA,kpsMT Ⅱ,cnf1,and PAI in the B2 group were significantly higher than those in the non-B2 group(P<0.05).The distribution rates of iutA,fyuA,kpsMT Ⅱ,cnf1,and PAI genes in the B2 group were significantly higher than those in the D group(P<0.05).Conclusion When treating bloodstream infections caused by E.coli,caution should be exercised in the use of drugs such as ceftriaxone,compound sulfamethoxazole,ampicillin,ampicillin sulbactam,cefazolin,and ciprofloxacin.When bloodstream infections are caused by phylogroup B2 E.coli,middle-stream urine culture should be performed simultaneously to confirm the source of infection and monitor the success rate of treatment.

Objective To explore the correlation between the expression of long non-coding RNA(lncRNA)brain ischemia-related factor(BIRF)and focally amplified lncRNA on chromosome 1(lncRNA FAL1)in serum and the degree of white matter lesions(WML)in patients with cerebral small vessel disease(CSVD).Methods From June 2021 to June 2023,102 CSVD patients admitted to Affiliated Hospital of Chengde Medical University were collected,and these patients were grouped into WML group(n=72)and non WML group(n=30)based on WML diagnostic criteria.According to the Fazekas score,the WML group was further grouped into mild WML group(n=24),moderate WML group(n=36)and severe WML group(n=12).Real-time fluorescence quantitative polymerase chain reaction(qRT-PCR)was applied to detect the levels of lncRNA BIRF and lncRNA FAL1 in serum.Pearson correlation was applied to analyze the correlation between serum lncRNA BIRF and lncRNA FAL1 levels.Receiver operating characteristic(ROC)curve was applied to analyze the diagnostic value of serum lncRNA BIRF and lncRNA FAL1 levels for severe WML in CSVD patients.Results The age(70.50±5.86 years),history of hypertension(Yes/No,43/29),history of diabetes(Yes/No,45/27),IL-33(68.35±6.80 pg/ml),IL-18(97.78±9.65 ng/L),ubiquitin carboxyl terminal hydrolase L1(UCH-L1)(0.29±0.10 μg/L)and lncRNA BIRF level(2.45±0.30)of patients in the WML group were higher than those in the non WML group(67.10±5.76 years,11/19,9/21,62.48±6.13 pg/ml,92.56±9.37 ng/L,0.24±0.06 μg/L,1.02±0.11),while the expression of serum lncRNA FAL1(0.52±0.10)was lower than that in the non WML group(1.04±0.15),with significant differences(t=2.683,4.518,8.978,4.085,2.510,2.550,25.346,20.500,all P<0.05).The serum lncRNA BIRF levels of CSVD patients in the mild,moderate and severe WML groups(2.23±0.23,2.47±0.31,2.82±0.42)were increased sequentially,while the expression of serum lncRNA FAL1(0.60±0.15,0.51±0.09,0.40±0.04)was decreased sequentially,with significant differences(F=14.913,13.899,all P<0.05).Pearson correlation analysis,the serum levels of lncRNA BIRF and lncRNA FAL1 in patients with WML were negatively correlated(r=-0.603,P<0.001),serum lncRNA BIRF was positively correlated with Fazekas score in WML patients(r=0.483,P<0.001),but serum lncRNA FAL1 was negatively correlated with Fazekas score(r=-0.507,P<0.001).The AUCs of serum lncRNA BIRF and lncRNA FAL1 levels alone and both combination for predicting severe WML in CSVD patients were 0.756(0.641～0.850),0.839(0.733～0.915)and 0.892(0.796～0.953),respectively,and the combination of the two was superior to the detection of serum lncRNA BIRF alone(Z=2.111,P=0.035).Conclusion The serum lncRNA BIRF level is increased and lncRNA FAL1 is reduced in patients with CSVD and WML,and both are related to the degree of WML in CSVD patients.

Objective:To systematically evaluate qualitative studies on the perceptions and feelings of nursing staffs implementing neonatal palliative care, aiming to provide insights for advancing clinical practice in China.Methods:The databases including China National Knowledge Infrastructure, Wanfang, VIP, Chinese Biomedical Literature Database, PubMed, CINAHL, Embase, Cochrane Library, Web of Science, and PsycINFO were included to retrieve the literature on the perceptions and feelings of nursing staffs from inception until March 28, 2024. The literature quality was assessed utilizing the Joanna Briggs Institute Australian Centre for Evidence-Based Health Care Quality Assessment Criteria for Qualitative Research (2016), and the findings were synthesized through Meta-integration techniques.Results:A total of 12 studies were included, yielding 46 themes were extracted; 8 categories were summarized and 3 synthesis results were obtained: nursing staffs experience both negative and positive aspects, the real-life challenges faced by nursing staffs in implementing neonatal palliative care, and the practical experiences and needs of nursing staffs regarding neonatal palliative care.Conclusions:It is crucial to continually address nursing staffs′ negative emotions and tackle challenges related to staffing, training, communication, and ethical dilemmas to ensure appropriate end-of-life symptom management in neonatal palliative care.

Objective:To analyze the effect of comprehensive rehabilitation intervention on the physical functioning of frail elderly persons.Methods:A total of 318 frail elderly persons were randomly divided into a control group ( n=164) and an observation group ( n=154) to test different interventions. Propensity score matching was used to balance the baseline information between the two groups 1∶1. A total of 200 cases were successfully matched, with 100 cases in each group. Both groups received drug treatment and routine nursing, while the observation group was additionally provided with comprehensive rehabilitation. Before and after 4 weeks of the treatment, both groups were evaluated using visual analogue scale (VAS) scoring for their perception of pain intensity, hand grip strength, gait speed, 6-minute walking distance (6MWD), 5 sit-up time, and the timed up and go test (TUGT). Results:There were no significant differences between the groups in any of the measurements before the experiment. Afterward, all of the outcome measures except gait speed were significantly better among the experimental group than among the controls, on average.Conclusions:Comprehensive rehabilitation can relieve pain, improve the walking, handgrip strength and exercise endurance of the frail elderly.

Brain edema belongs to the category of "stroke" and "true headache", while Traditional Chinese Medicine mostly understands its core disease mechanisms from the perspectives of stasis, deficiency, and heat, and mostly treats the disease by using warming yang to induce diuresis and eliminating stasis to remove water. Wuling Powder has been lauded as the "first party to typhoid and relieving diuresis", which is used to cure clearing damp and promoting diuresis and warming yang and transforming qi, and has been clinically used in the treatment of brain edema caused by various causes such as head trauma, intracerebral hemorrhage, cerebral infarction, and intracranial space occupying, all with remarkable efficacy. Wuling Powder improves cellular energy supply, scavenges excess oxygen radicals and calcium ions in brain tissue, and reduces the damage to brain tissue caused by vascular inflammatory factors and regulates aquaporins and vascular endothelial growth factor, thereby achieving therapeutic effects.

For wild natural medicine, unanticipated biodiversity as species or varieties with similar morphological characteristics and sympatric distribution may co-exist in a single batch of medical materials, which affects the efficacy and safety of clinical medication. DNA barcoding as an effective species identification tool is limited by its low sample throughput nature. In this study, combining DNA mini-barcode, DNA metabarcoding and species delimitation method, a novel biological sources consistency evaluation strategy was proposed, and high level of interspecific and intraspecific variations were observed and validated among 5376 Amynthas samples from 19 sampling points regarded as "Guang Dilong" and 25 batches of proprietary Chinese medicines. Besides Amynthas aspergillum as the authentic source, 8 other Molecular Operational Taxonomic Units (MOTUs) were elucidated. Significantly, even the subgroups within A. aspergillum revealed here differ significantly on chemical compositions and biological activity. Fortunately, this biodiversity could be controlled when the collection was limited to designated areas, as proved by 2796 "decoction pieces" samples. This batch biological identification method should be introduced as a novel concept regarding natural medicine quality control, and to offer guidelines for in-situ conservation and breeding bases construction of wild natural medicine.

Objective To investigate the correlation of serum interleukin 33(IL-33) level and regional cerebral blood flow(rCBF) in white matter lesions with the severity of white matter ischemic lesions(WMILs) in patients with WMILs. Methods A total of 104 patients with WMILs admitted to our hospital from November 2021 to April 2022 were divided into mild group(n=36),moderate group(n=42),and severe group(n=26) according to the Fazekas scale scores. Age,histories of hypertension and diabetes,and data of total cholesterol,triglyceride,high-density lipoprotein cholesterol,low-density lipoprotein cholesterol,homocysteine,glycosylated hemoglobin,serum creatinine,and urea were collected. The serum IL-33 level was measured. The values of rCBF in the centrum semiovale and periventricular area were measured by arterial spin labeling. Multivariate Logistic regression was used to analyze the correlation of serum IL-33 level and rCBF values in the centrum semiovale and periventricular area with the severity of WMILs. Results The age,hypertension,creatinine,and homocysteine in the moderate and severe groups were significantly higher than those in the mild group(P<0.05),and the IL-33 level and rCBF values in the severe group were significantly lower than those in the mild and moderate groups(P<0.01). After adjusting for hypertension,age,and other factors,Logistic regression analysis showed that IL-33 level and rCBF values in the periventricular area and centrum semiovale were protective factors for the increased severity of WMILs[odds ratio(OR)=0.818,95% confidence interval(CI) 0.715-0.935,P=0.003;OR=0.659,95%CI 0.506-0.859,P=0.002;OR=0.817,95%CI 0.692-0.966,P=0.018)]. Spearman rank correlation analysis showed that serum IL-33 level and rCBF values in the periventricular area and centrum semiovale were negatively correlated with the severity of WMILs(r=-0.575,P<0.01;r=-0.607,P<0.01;r=-0.644,P<0.01). Conclusion The IL-33 level and rCBF values in the periventricular area and centrum semiovale may be related to the severity of WMILs.