Stroke is one of the leading causes of disability and mortality worldwide. Research into its mechanisms and the development of therapeutic strategies heavily rely on animal models that accurately replicate the pathological features of human disease. An ideal animal model for stroke should not only reproduce the neurological deficits and pathological changes observed in clinical patients but also demonstrate good reproducibility and translational value. This review focuses on the preparation and evaluation methods of ischemic stroke animal models. Firstly, it elaborates on the selection criteria, advantages, and disadvantages of experimental animals, including rodents (rats, mice) and non-rodents (non-human primates, miniature pigs, rabbits, zebrafish). Secondly, it provides a detailed overview of the modeling principles, key procedures, and application scopes for ischemic stroke models and hemorrhagic stroke models. Furthermore, the review summarizes advances in the applications of emerging technologies—including gene editing [e.g., clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) gene editing], multimodal imaging (e.g., two-photon microscopy, photoacoustic imaging), artificial intelligence, optogenetics, 3D bioprinting, organoid models, and multi-omics–in model optimization, precise assessment, and mechanistic investigation. Finally, based on a systematic analysis of relevant domestic and international literature from 2019 to 2024, this review discusses model selection strategies based on research objectives, a multidimensional evaluation system encompassing behavioral, imaging, and molecular pathological assessments, and envisions future directions involving technological integration to achieve model precision and individualization. This article aims to provide a comprehensive methodological reference to help researchers select appropriate animal models of stroke according to specific scientific questions.

ObjectiveTo investigate the association between noninvasive liver fibrosis markers and carotid plaque （CP） in patients with lean metabolic dysfunction-associated fatty liver disease （MAFLD）， and to provide a basis for screening high-risk populations. MethodsA total of 957 patients with lean MAFLD who underwent physical examination in Subei People’s Hospital from January 2021 to June 2023 was enrolled as the observation cohort， with the presence or absence of CP as the outcome， and fibrosis-4 （FIB-4） index and nonalcoholic fatty liver disease fibrosis score （NFS） were used to assess liver fibrosis degree. The independent-samples t test was used for comparison of normally distributed continuous data between two groups， and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups； the chi-square test was used for comparison of categorical data between two groups. The multivariate logistic regression analysis， the restricted cubic spline analysis， the receiver operating characteristic curve， and the mediation effect analysis were used to investigate the association between liver fibrosis degree and CP. ResultsThe prevalence rate of CP was 36.6% in the lean MAFLD population. Compared with the non-CP group（n=607）， the CP group （n=350） had a significantly higher proportion of male patients， a significantly higher proportion of patients with smoking/diabetes/hypertension， and significantly higher levels of age， creatinine， blood urea nitrogen， triglycerides， fasting blood glucose， aspartate aminotransferase， aspartate aminotransferase/alanine aminotransferase ratio， NFS， and FIB-4 index， as well as significantly lower levels of platelet count and albumin （all P<0.05）. The multivariate logistic regression analysis showed that after adjustment for confounding factors， FIB-4 index （odds ratio［OR］=2.979， 95% confidence interval［CI］：2.141 — 4.219， P<0.001） and NFS （OR=1.747， 95%CI： 1.499 — 2.046， P<0.001） were positively correlated with CP. Both FIB-4 index and NFS had a good value in predicting CP. Hypertension had a significant indirect effect on the prevalence rate of CP through its impact on liver fibrosis markers， and its mediating effect accounted for 39.5% — 40.8% of the total effect （P<0.001）. ConclusionIn patients with lean MAFLD， NFS and FIB-4 index are significantly positively correlated with the prevalence rate of CP， and they can be used as potential epidemiological predictive indicators. Liver fibrosis markers may play a mediating role in the association between hypertension and CP. Interventions targeting hypertension and liver fibrosis markers may help to prevent and delay the progression of CP.

AIM: To compare the progression of myopia in children wearing orthokeratology lenses combined with low-concentration atropine before and after drug withdrawal, to determine the rebound effect of drug withdrawal in orthokeratology lens wearers, and to analyze its causes based on changes in pupil diameter.METHODS:A prospective case-control study was conducted to collect 80 children with myopia who were treated with orthokeratology lenses combined with 0.01% atropine ophthalmic gel at the Xi'an No.1 Hospital from January to June 2022. One year later, they were divided into a drug withdrawal group(Group A, 40 cases)and a continuous medication group(Group B, 40 cases)based on whether they stopped taking the medication. The progression of myopia before and after drug withdrawal was observed by analyzing changes in axial length(AL)and spherical equivalent(SE)in the group A within 1 a before and after drug withdrawal. The changes in AL, pupil diameter(PD), and SE were compared between the group A and group B within 2 a, and the correlation between PD and AL growth was analyzed.RESULTS:In the group A, the AL increased by 0.17±0.23 and 0.29±0.18 mm at 0.5 and 1 a after drug withdrawal, respectively, which were both greater than before drug withdrawal(t=5.318, 2.983, both P<0.001). There was no statistically significant difference in SE growth between the two time points(P>0.05). There were no statistically significant differences in AL and PD between the group A and group B at baseline, 0.5 and 1 a during combined medication(all P>0.05). At 1.5 a, the AL growth of the group A was greater than that of the group B(0.32±0.27 mm vs 0.26±0.20 mm, t=7.363, P<0.001), and the PD was smaller than that of the group B(3.60±1.25 mm vs 4.12±1.92 mm, t=-7.541, P<0.001). At 2 a, the AL growth of the group A was greater than that of the group B(0.44±0.18 mm vs 0.32±0.14 mm, t=5.709, P<0.001), and the PD was smaller than that of the group B(3.67±1.31 mm vs 4.02±1.67 mm, t=-4.281, P<0.001). Correlation analysis showed a negative correlation between PD and AL growth at 0.5 and 1 a follow-ups over 2 a(R2=-0.156, -0.190, both P<0.001).CONCLUSION: After stopping low-concentration atropine in children wearing orthokeratology lenses, AL increased more rapidly than before drug withdrawal, PD decreased, and SE changed little. Compared with continuous medication, discontinuation of medication led to faster progression of AL with little change in diopter, and the larger the PD during orthokeratology lens wear, the slower the progression of AL.

ObjectiveTo investigate the effect and underlying mechanism of the Wulao Qisun prescription on pathological new bone formation in ankylosing spondylitis （AS）. MethodsSynovial fibroblasts were isolated from the hip joints of AS patients and observed under a microscope to assess cell morphology. The cells were identified using immunofluorescence staining. The isolated AS fibroblasts were divided into blank group， low drug-containing serum group， medium drug-containing serum group， high drug-containing serum group， and positive drug group. After drug intervention， cell proliferation was measured using the cell counting kit-8 （CCK-8） assay to observe fibroblast growth and determine the optimal intervention time. Alkaline phosphatase （ALP） activity was measured using the alkaline phosphatase assay. Protein expression of osteocalcin （OCN）， osteopontin （OPN）， and runt-related transcription factor 2 （Runx2） was detected by Western blot. The mRNA expression levels of Wnt5a， β-catenin， and Dickkopf-1 （DKK-1） were measured by real-time quantitative polymerase chain reaction （Real-time PCR）. ResultsCompared with the blank group， each drug-containing serum group of Wulao Qisun prescription and the positive drug group inhibited the proliferation of AS fibroblasts and reduced ALP expression （P<0.01）. Compared with the blank group， the low drug-containing serum group of Wulao Qisun prescription downregulated β-catenin mRNA expression （P<0.05）. The medium and high drug-containing serum groups and the positive drug group significantly downregulated Wnt5a and β-catenin mRNA expression （P<0.05， P<0.01）， with the positive drug group showing the most pronounced effect （P<0.01）. The high drug-containing serum group and the positive drug group significantly upregulated DKK-1 mRNA expression （P<0.01）. Compared with the blank group， the low drug-containing serum group of Wulao Qisun prescription inhibited the expression of OPN and Runx2 proteins （P<0.05， P<0.01）， while the medium and high drug-containing serum groups and the positive drug group inhibited the expression of OCN， OPN， and Runx2 proteins （P<0.05， P<0.01）. ConclusionThe Wulao Qisun prescription can inhibit the proliferation and osteogenic differentiation of AS fibroblasts， thereby delaying the formation of pathological new bone in AS. The possible mechanism involves the regulation of Wnt/β-catenin-related gene expression， further inhibiting the transcription of downstream target genes.

With the widespread use of antibiotics, drug-resistant bacterial infections have become a significant threat to human health. Finding new antibacterial strategies that can effectively control drug-resistant bacterial infections has become an urgent task. Unlike small molecule drugs that target bacterial proteins, antisense oligonucleotide (ASO) can target genes related to bacterial resistance, pathogenesis, growth, reproduction and biofilm formation. By regulating the expression of these genes, ASO can inhibit or kill bacteria, providing a novel approach for the development of antibacterial drugs. To overcome the challenge of delivering antisense oligonucleotide into bacterial cells, various drug delivery systems have been applied in this field, including cell-penetrating peptides, lipid nanoparticles and inorganic nanoparticles, which have injected new momentum into the development of antisense oligonucleotide in the antibacterial realm. This review summarizes the current development of small nucleic acid drugs, the antibacterial mechanisms, targets, sequences and delivery vectors of antisense oligonucleotide, providing a reference for the research and development of antisense oligonucleotide in the treatment of bacterial infections.

ObjectiveTo observe the effects of electroacupuncture with "tonifying the kidney and dispelling stasis" acupoint prescription on sexual function in diabetic erectile dysfunction （DMED）model rats， and to explore its possible mechanism of action. MethodsSPF male SD rats were randomly divided into 10 each in blank group， model group， Tadalafil group， and electroacupuncture group. DMED rat model was prepared by high glucose and high fat diet combined with intraperitoneal injection of streptozotocin. After successful modelling， rats in the electroacupuncture group were given electroacupuncture intervention of "tonifying the kidney and dispelling stasis" acupoint prescription once every other day； Tadalafil group was given Tadalafil solution 0.5 mg/kg·d by gavage， and the blank group， model group and electroacupuncture group were given 10 ml/kg pure water by gavage once a day. Each group was intervened for 30 days. The body mass and blood glucose level of the rats were detected on the 1st， 8th， 15th， 22nd days and at the end of the intervention， respectively. At the end of the intervention， the penile erection of the rats was observed by using the apomorphine test； the level of plasma endothelial cell microparticles （EMPs）was detected by flow cytometry； the histopathological morphology of the penile cavernous body was observed by HE staining， and the pathological morphology of the endothelial cells of the penile vasculature was observed by electron microscopy. Serum sex hormones including testosterone （T）， follicle stimulating hormone （FSH）， luteinising hormone （LH） and vascular endothelial function-related factors including vascular endothelial growth factor （VEGF）， endothelin-1 （ET-1）， lectin-like oxidized low-density lipoprotein receptor-1 （LOX-1）， soluble E-selectin （sE-selectin）， and soluble intercellular adhesion molecule-1 （sICAM-1） were measured by ELISA method. ResultsCompared with blank group， the model group， Tadalafil group， and electroacupuncture group all had lower body mass and higher blood glucose levels at each time of testing （P＜0.01）. Compared with the blank group， the number of penile erections reduced in the model group， the level of CD31⁺ EMPs increased， the levels of serum T， FSH， LH， and VEGF reduced， and the levels of serum ET-1， LOX-1， sE-selectin， and sICAM-1 increased （P＜0.01）. Compared with the model group， the Tadalafil group and the electroacupuncture group showed an increased number of penile erections decreased level of CD31⁺ EMPs， increased levels of serum T， FSH， LH， and VEGF， and decreased levels of serum ET-1， LOX-1， sE-selectin， and sICAM-1 （P＜0.01）. Compared with the Tadalafil group， serum T， FSH， LH， VEGF levels increased and ET-1， LOX-1 levels decreased in the electroacupuncture group （P＜0.05 or P＜0.01）. HE staining and electron microscopic observation revealed that there was severe pathological damage to the cavernous tissue of the penis and vascular endothelial cells of the rat in the model group， which was ameliorated to a certain degree in both Tadalafil group and electroacupuncture group. ConclusionThe electroacupuncture prescription of "tonifying the kidney and dispelling stasis" can improve the erectile dysfunction of DMED rats， which is comparable to the effect of Tadalafi. Its mechanism of action may be related to the regulation of vascular endothelial function.

Background: En bloc resection is recommended for the treatment of malignant and aggressive benign spinal tumors; however, it often requires a combined anterior-posterior approach, which is usually accompanied by longer surgical duration, increased blood loss, larger trauma, and surgical complexity. The present study describes a novel rotation-reversion technique for en bloc resection of the thoracic and upper lumbar spinal tumors using a posterior-only approach and evaluate its safety and efficacy. Methods: Thirteen patients with thoracic and upper lumbar (L1-L3) spinal tumors were treated with en bloc resection using the rotation-reversion technique through a posterior-only approach at our institution between 2015 and 2023. The clinical characteristics and surgical results of the patients were reviewed and analyzed. Results: Posterior-only en bloc resection was performed successfully in all 13 patients using the rotation-reversion technique, with a median follow-up of 30.4 months (range, 6–74 months). The average maximum size of these 13 tumors was 5.7 × 5.8 × 4.8 cm.The mean operation time and blood loss were 458.5 minutes (range, 220–880 minutes) and 3,146.2 mL (range, 1,000–6,000 mL), respectively, with 4 of the 13 patients (30.8%) experiencing perioperative complications. Negative margins were achieved in all the 13 patients (100%). One patient experienced local recurrence (7.7%) and 1 patient experienced instrumentation failures. Interbody fusion was confirmed in 11 of the 13 patients (84.6%), with a median fusion time of 6.9 months. All of the 13 patients experienced varying degrees of mild postoperative neurological deficits owing to resection of the nerve roots affected by tumor invasion of the vertebrae. No vessel injury or postoperative neurological paralysis occurred, except 1 patient who had been completely paralyzed before surgery. Conclusions The rotation-reversion technique is an effective procedure for en bloc resection of selected thoracic and upper lumbar spinal tumors through the posterior-only approach.

Background: En bloc resection is recommended for the treatment of malignant and aggressive benign spinal tumors; however, it often requires a combined anterior-posterior approach, which is usually accompanied by longer surgical duration, increased blood loss, larger trauma, and surgical complexity. The present study describes a novel rotation-reversion technique for en bloc resection of the thoracic and upper lumbar spinal tumors using a posterior-only approach and evaluate its safety and efficacy. Methods: Thirteen patients with thoracic and upper lumbar (L1-L3) spinal tumors were treated with en bloc resection using the rotation-reversion technique through a posterior-only approach at our institution between 2015 and 2023. The clinical characteristics and surgical results of the patients were reviewed and analyzed. Results: Posterior-only en bloc resection was performed successfully in all 13 patients using the rotation-reversion technique, with a median follow-up of 30.4 months (range, 6–74 months). The average maximum size of these 13 tumors was 5.7 × 5.8 × 4.8 cm.The mean operation time and blood loss were 458.5 minutes (range, 220–880 minutes) and 3,146.2 mL (range, 1,000–6,000 mL), respectively, with 4 of the 13 patients (30.8%) experiencing perioperative complications. Negative margins were achieved in all the 13 patients (100%). One patient experienced local recurrence (7.7%) and 1 patient experienced instrumentation failures. Interbody fusion was confirmed in 11 of the 13 patients (84.6%), with a median fusion time of 6.9 months. All of the 13 patients experienced varying degrees of mild postoperative neurological deficits owing to resection of the nerve roots affected by tumor invasion of the vertebrae. No vessel injury or postoperative neurological paralysis occurred, except 1 patient who had been completely paralyzed before surgery. Conclusions The rotation-reversion technique is an effective procedure for en bloc resection of selected thoracic and upper lumbar spinal tumors through the posterior-only approach.

Background: En bloc resection is recommended for the treatment of malignant and aggressive benign spinal tumors; however, it often requires a combined anterior-posterior approach, which is usually accompanied by longer surgical duration, increased blood loss, larger trauma, and surgical complexity. The present study describes a novel rotation-reversion technique for en bloc resection of the thoracic and upper lumbar spinal tumors using a posterior-only approach and evaluate its safety and efficacy. Methods: Thirteen patients with thoracic and upper lumbar (L1-L3) spinal tumors were treated with en bloc resection using the rotation-reversion technique through a posterior-only approach at our institution between 2015 and 2023. The clinical characteristics and surgical results of the patients were reviewed and analyzed. Results: Posterior-only en bloc resection was performed successfully in all 13 patients using the rotation-reversion technique, with a median follow-up of 30.4 months (range, 6–74 months). The average maximum size of these 13 tumors was 5.7 × 5.8 × 4.8 cm.The mean operation time and blood loss were 458.5 minutes (range, 220–880 minutes) and 3,146.2 mL (range, 1,000–6,000 mL), respectively, with 4 of the 13 patients (30.8%) experiencing perioperative complications. Negative margins were achieved in all the 13 patients (100%). One patient experienced local recurrence (7.7%) and 1 patient experienced instrumentation failures. Interbody fusion was confirmed in 11 of the 13 patients (84.6%), with a median fusion time of 6.9 months. All of the 13 patients experienced varying degrees of mild postoperative neurological deficits owing to resection of the nerve roots affected by tumor invasion of the vertebrae. No vessel injury or postoperative neurological paralysis occurred, except 1 patient who had been completely paralyzed before surgery. Conclusions The rotation-reversion technique is an effective procedure for en bloc resection of selected thoracic and upper lumbar spinal tumors through the posterior-only approach.

OBJECTIVE: To evaluate the clinical efficacy and safety of Yangxue Qingnao Pills (YXQNP) combined with amlodipine in treating patients with grade 1 hypertension. METHODS: This is a multicenter, randomized, double-blind, and placebo-controlled study. Adult patients with grade 1 hypertension of blood deficiency and Gan (Liver)-yang hyperactivity syndrome were randomly divided into the treatment or the control groups at a 1:1 ratio. The treatment group received YXQNP and amlodipine besylate, while the control group received YXQNP's placebo and amlodipine besylate. The treatment duration lasted for 180 days. Outcomes assessed included changes in blood pressure, Chinese medicine (CM) syndrome scores, symptoms and target organ functions before and after treatment in both groups. Additionally, adverse events, such as nausea, vomiting, rash, itching, and diarrhea, were recorded in both groups. RESULTS: A total of 662 subjects were enrolled, of whom 608 (91.8%) completed the trial (306 in the treatment and 302 in the control groups). After 180 days of treatment, the standard deviations and coefficients of variation of systolic and diastolic blood pressure levels were lower in the treatment group compared with the control group. The improvement rates of dizziness, headache, insomnia, and waist soreness were significantly higher in the treatment group compared with the control group (P<0.05). After 30 days of treatment, the overall therapeutic effects on CM clinical syndromes were significantly increased in the treatment group as compared with the control group (P<0.05). After 180 days of treatment, brachial-ankle pulse wave velocity, ankle brachial index and albumin-to-creatinine ratio were improved in both groups, with no statistically significant differences (P>0.05). No serious treatment-related adverse events occurred during the study period. CONCLUSIONS Combination therapy of YXQNP with amlodipine significantly improved symptoms such as dizziness and headache, reduced blood pressure variability, and showed a trend toward lowering urinary microalbumin in hypertensive patients. These findings suggest that this regimen has good clinical efficacy and safety. (Registration No. ChiCTR1900022470).
Humans ; Amlodipine/adverse effects* ; Drugs, Chinese Herbal/adverse effects* ; Male ; Female ; Hypertension/complications* ; Middle Aged ; Treatment Outcome ; Drug Therapy, Combination ; Adult ; Blood Pressure/drug effects* ; Double-Blind Method ; Aged ; Antihypertensive Agents/adverse effects*