OBJECTIVES: To evaluate preterm white matter injury (PWMI) in neonatal rats using multimodal magnetic resonance imaging (MRI) combined with histological assessments and to explore its underlying mechanisms. METHODS: Healthy 3-day-old Sprague-Dawley neonatal rats were randomly divided into a sham operation group and a PWMI group (n=12 in each group). A PWMI model was established in neonatal rats through hypoxia-ischemia. Laser speckle imaging was used to observe changes in cerebral oxygen saturation and blood flow at different time points post-modeling. Multimodal MRI was employed to assess the condition of white matter injury, while hematoxylin-eosin staining was utilized to observe morphological changes in the striatal area on the injured side. Immunofluorescence staining was performed to detect the proliferation and differentiation of oligodendrocyte precursor cells. RESULTS: At 0, 6, 12, 24, and 72 hours post-modeling, the relative blood flow and relative oxygen saturation on the injured side in the PWMI group were significantly lower than those in the sham operation group (P<0.05). At 24 hours post-modeling, T2-weighted imaging showed high signals in the white matter of the injured side in the PWMI group, with relative apparent diffusion coefficient values and Lorenz differential values being lower than those in the sham operation group (P<0.001); additionally, the arrangement of nerve cells in the PWMI group was disordered, and the number of EdU⁺PDGFR-α⁺ cells was higher than that in the sham operation group (P<0.001). At 28 days post-modeling, the relative fractional anisotropy values, the number of EdU⁺Olig2⁺ cells, and the fluorescence intensity of myelin basic protein and neurofilament protein 200 in the white matter region of the PWMI group were all lower than those in the sham operation group (P<0.001). CONCLUSIONS Multimodal MRI can evaluate early and long-term changes in PWMI in neonatal rat models in vivo, providing both imaging and pathological evidence for the diagnosis and treatment of PWMI in neonates. Hypoxia-ischemia inhibits the proliferation and differentiation of oligodendrocyte precursor cells in neonatal rats, leading to PWMI.
Animals ; Rats, Sprague-Dawley ; Magnetic Resonance Imaging/methods* ; Rats ; White Matter/injuries* ; Animals, Newborn ; Female ; Multimodal Imaging ; Male ; Hypoxia-Ischemia, Brain/pathology*

OBJECTIVE: To evaluate the clinical effect and safety of acupuncture manipulation on treatment of intractable facial paralysis (IFP), and verify the practicality and precision of the Anzhong Facial Paralysis Precision Scale (Eyelid Closure Grading Scale, AFPPS-ECGS). METHODS: A multicentre, single-blind, randomized controlled trial was conducted from October 2022 to June 2024. Eighty-nine IFP participants were randomly assigned to an ordinary acupuncture group (OAG, 45 cases) and a characteristic acupuncture group (CAG, 44 cases) using a random number table method. The main acupoints selected included Yangbai (GB 14), Quanliao (SI 18), Yingxiang (LI 20), Shuigou (GV 26), Dicang (ST 4), Chengjiang (CV 24), Taiyang (EX-HN 5), Jiache (ST 6), Fengchi (GB 20), and Hegu (LI 4). The OAG patients received ordinary acupuncture manipulation, while the CAG received characteristic acupuncture manipulation. Both groups received acupuncture treatment 3 times a week, with 10 times per course, lasting for 10 weeks. Facial recovery was assessed at baseline and after the 1st, 2nd and 3rd treatment course by AFPPS-ECGS and the House-Brackmann (H-B) Grading Scale. Infrared thermography technology was used to observe the temperature difference between healthy and affected sides in various facial regions. Adverse events and laboratory test abnormalities were recorded. The correlation between the scores of the two scales was analyzed using Pearson correlation coefficient. RESULTS: After the 2nd treatment course, the two groups showed statistically significant differences in AFPPS-ECGS scores (P<0.05), with even greater significance after the 3rd course (P<0.01). Similarly, H-B Grading Scale scores demonstrated significant differences between groups following the 3rd treatment course (P<0.05). Regarding temperature measurements, significant differences in temperatures of frontal and ocular areas were observed after the 2nd course (P<0.05), becoming more pronounced after the 3rd course (P<0.01). Additionally, mouth corner temperature differences reached statistical significance by the 3rd course (P<0.05). No safety-related incidents were observed during the study. Correlation analysis revealed that the AFPPS-ECGS and the H-B Grading Scale were strongly correlated (r=0.86, 0.91, 0.93, and 0.91 at baseline, and after 1st, 2nd, and 3rd treatment course, respectively, all P<0.01). CONCLUSIONS Acupuncture is an effective treatment for IFP, and the characteristic acupuncture manipulation enhances the therapeutic effect. The use of the AFPPS-ECGS can more accurately reflect the recovery status of patients with IFP. (Trial registration No. ChiCTR2200065442).
Humans ; Acupuncture Therapy/methods* ; Facial Paralysis/therapy* ; Female ; Male ; Middle Aged ; Adult ; Treatment Outcome ; Acupuncture Points ; Aged

Objective:To explore the diagnosis and minimal invasive treatment of neonatal pyriform sinus fistula. Methods:A retrospective analysis was conducted on the clinical data of newborns diagnosed with pyriform sinus fistula in the Children's Hospital, Zhejiang University School of Medicine from January 2016 to December 2023, including the diagnostic process and treatment methods. Results:There were 8 children, 2 males and 6 females, with 7 cases on the left side and 1 case on the right side. Six cases revealed a lump in the fetal neck during prenatal examination, and two cases were found to have a neck mass after birth. All cases presented with varying degrees of respiratory disorders. After admission, all patients underwent neck ultrasound and contrast-enhanced CT examination. Neck ultrasound showed cystic masses, with 3 of the cysts accompanied by septa, and an air-fluid level was observed in the cysts in 6 cases from contrast-enhanced CT. All patients underwent ultrasound-guided neck mass puncture and/or tube placement combined with endoscopic electrocauterization. The cystic fluid was found to be yellow and thin, with no signs of infection. The surgical operations were uneventful, and the follow-up time ranged from 12 to 72 months postoperatively. There were no complications such as hoarseness, and no recurrence cases were reported. Conclusion:Neonatal pyriform sinus fistula is often characterized by a large cystic mass in the neck combined with respiratory depression. The presence of an air-fluid level in the cyst from contrast-enhanced CT can be considered an important basis for early diagnosis of pyriform sinus fistula. Ultrasound-guided puncture combined with endoscopic electrocauterization is minimally invasive and safe, making it a suitable minimal invasive treatment for neonatal pyriform sinus fistula.
Humans ; Female ; Male ; Pyriform Sinus/surgery* ; Retrospective Studies ; Infant, Newborn ; Cautery/methods* ; Endoscopy ; Fistula/surgery* ; Punctures ; Tomography, X-Ray Computed

Objective To evaluate the short-term efficacy of Huoxue Xiaozhong Powder(i.e.,Shuangbai San)for the treatment of patients with mild-to-moderate knee osteoarthritis(KOA)of qi stagnation and blood stasis syndrome.Methods Sixty patients with mild-to-moderate KOA of qi stagnation and blood stasis syndrome were randomly divided into the treatment group and the control group,with 30 cases in each group.The treatment group was treated with external application of Huoxue Xiaozhong Powder,and the control group was treated with external application of Voltaren(diclofenac diethylamide emulsion).Both groups were treated for one week as a course.The changes of visual analogue scale(VAS)score,Western Ontario and McMaster Universities Osteoarthritis Index(WOMAC)score and erythrocyte sedimentation rate(ESR),C-reactive protein(CRP)level and synovial thickness under ultrasound in the two groups before and after treatment were observed.Moreover,the clinical efficacy and safety of the two groups were evaluated.Results(1)After one week of treatment,the total effective rate of the treatment group was 93.33%(28/30),and that of the control group was 73.33%(22/30).The intergroup comparison(tested by rank sum test)showed that the clinical efficacy of the treatment group was significantly superior to that of the control group(P＜0.05).(2)After treatment,the VAS score,WOMAC score,ESR,CRP level and synovial thickness under ultrasound in the two groups were significantly improved compared with those before treatment(P＜0.01),and the treatment group had stronger effect on the improvement of VAS score,WOMAC score,ESR,CRP level and synovial thickness under ultrasound than the control group(P＜0.01).(3)During treatment,no obvious adverse reactions such as skin redness,swelling and itching occurred in the two groups of patients,which had a high safety.Conclusion For the patients with mild-to-moderate KOA of qi stagnation and blood stasis syndrome,the use of Huoxue Xiaozhong Powder for external treatment alone can also achieve good short-term clinical effects,which can effectively alleviate the symptoms of pain,and reduce the levels of inflammatory indicators and synovial thickness.

Gorham-Stout disease(GSD)is a sporadic chronic disease characterized by progressive bone dissolution,absorption,and disappearance along with lymphatic vessel infiltration in bone-marrow cavities.Although the osteolytic mechanism of GSD has been widely studied,the cause of lymphatic hyperplasia in GSD is rarely investigated.In this study,by comparing the RNA expression profile of osteoclasts(OCs)with that of OC precursors(OCPs)by RNA sequencing,we identified a new factor,semaphorin 3A(Sema3A),which is an osteoprotective factor involved in the lymphatic expansion of GSD.Compared to OCPs,OCs enhanced the growth,migration,and tube formation of lymphatic endothelial cells(LECs),in which the expression of Sema3A is low compared to that in OCPs.In the presence of recombinant Sema3A,the growth,migration,and tube formation of LECs were inhibited,further confirming the inhibitory effect of Sema3A on LECs in vitro.Using an LEC-induced GSD mouse model,the effect of Sema3A was examined by injecting lentivirus-expressing Sema3A into the tibiae in vivo.We found that the overexpression of Sema3A in tibiae suppressed the expansion of LECs and alleviated bone loss,whereas the injection of lentivirus expressing Sema3A short hairpin RNA(shRNA)into the tibiae caused GSD-like phenotypes.Histological staining further demonstrated that OCs decreased and osteocalcin increased after Sema3A lentiviral treatment,compared with the control.Based on the above results,we propose that reduced Sema3A in OCs is one of the mechanisms contributing to the pathogeneses of GSD and that expressing Sema3A represents a new approach for the treatment of GSD.

BACKGROUND:Medical hydrogels are new functional polymer materials with three-dimensional structural networks and excellent biocompatibility,which have been widely studied in the field of tissue engineering and drug carriers,but the research on the combination of medical hydrogels and Chinese medicine for the treatment of diseases based on tissue engineering is still in the early exploration stage.Therefore,through the analysis of the mechanism of the role of medical hydrogels,the integration of medical hydrogels and Chinese medicine in the research of the joint application of the article,can better provide ideas for scientific researchers,and the joint application of Chinese medicine and medical hydrogels is of great significance. OBJECTIVE:To explore the strategy and significance of Chinese medicine combined with medical hydrogel for disease treatment based on tissue engineering research. METHODS:PubMed and CNKI were used to retrieve articles about the application of Chinese medicine combined with medical hydrogel in tissue engineering from January 2010 to November 2022,with the Chinese and English search terms"hydrogel,traditional Chinese medicine,drug carrier,tissue engineering".After the initial screening of all articles according to the inclusion and exclusion criteria,the 61 articles with high relevance were retained for review. RESULTS AND CONCLUSION:(1)Although the application of Chinese medicine combined with medical hydrogel is involved in intra-articular,intra-tissue organ,soft tissue wounds,tissue engineering,etc.,except for the clinical application of Chinese medicine combined with hydrogel dressing for soft tissue injury,other aspects are still in the experimental stage.(2)The development of Chinese medicine combined with medical hydrogel has great potential and development prospects,but there is a certain difficulty in the manufacture of the gel with high-performance requirements,and it is difficult to master the physical and chemical properties precisely.(3)At present,the comprehensive view of injectable hydrogel with the characteristics of easy to use,its joint use of Chinese medicine can be extended to a wider range,can be used for joint,organ,tissue engineering-related disease treatment.Smart hydrogel has high sensitivity and reversible transformation can also meet the use of the special environment.During the combined use of Chinese medicine,it also needs to understand the mechanism of action of Chinese medicine components.(4)The strategy of combining Chinese medicine with medical hydrogels for disease treatment should start with matching the therapeutic effects of Chinese medicine on organs,tissues and cells combined with appropriate types of medical hydrogels to make up for the shortcomings of traditional Chinese medicine delivery methods and frequent drug delivery.In tissue engineering,hydrogels can be loaded with stem cells after Chinese medicine intervention,or with both Chinese medicine and stem cells for disease treatment.(5)In future research of combined Chinese medicine and medical hydrogel application,we also need to consider:we should ensure that the biological properties of medical hydrogel can be quantified,and grasp the characteristics of hydrogel with different manufacturing processes of different materials to produce the required medical hydrogel that meets the application conditions.In Chinese medicine,we need to comprehensively understand and analyze the therapeutic effects and application mechanisms of known Chinese medicine monomer and Chinese medicine compound extracts,so as to achieve a more perfect combination between Chinese medicine and medical hydrogel under a more clear mechanism.With the continuous improvement of medical science and technology innovation,the medical hydrogel can be innovatively combined with other traditional treatment methods of Chinese medicine,such as acupuncture,massage,cupping and so on,to be used from multiple angles.

Objective: To examine the developmental trajectory of fine motor ability in schoolage children with attention deficit hyperactivity disorder (ADHD) for two years, so as to provide scientific evidence to promote motor development in ADHD children. Methods: From April to June 2019, 31 children aged 6-8 years old were selected from a public elementary school. They were diagnosed with ADHD by two psychiatric professionals according to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-V) criteria. Additionally, 31 typical developmental children, matched for age, sex and IQ with the ADHD group, were recruited as the control group. Fine motor ability was assessed with tasks of hand manual dexterity in Movement Assessment Battery for Children-2 (MACB-2), and a followup assessment was conducted from April to June 2021. The development changes of fine motor ability between two groups of children were compared by using t test and repeated measures analysis of variance. Results: Between baseline and followup periods after two years, the total score of hand fine motor in the ADHD group did not show significant improvement (7.4±3.0, 8.0±3.4; t=-1.05, P>0.05), while there was a small effect size improvement in typically developing control group (9.5±2.1, 10.5±2.4; t=-2.12, effect size=0.38, P<0.05). Followup after two years, coin/peg throwing scores with dominant hand improved between ADHD group and control group (7.0±3.3, 9.5±3.2; 8.4±2.8, 11.6±1.6) (t=-3.74, -6.33, P<0.01; effect size=0.67, 1.14), with a smaller improvement in the ADHD group. The score for threading beads/threads decreased in between ADHD group and control group (7.9±2.4, 5.8±3.1; 9.2±1.1, 8.2±1.9) (t=3.89, 2.78, P<0.01; effect size=0.70, 0.50), with a greater decrease in the ADHD group. Conclusions The development speed of fine motor ability in children with ADHD aged 6-8 is slow and continues to lag behind normal developmental children. Fine motor development in children with ADHD should be closely monitored, and targeted interventions should be implemented when necessary.

AIM To prepare the soluble microneedles of Aconitum brachypodum Diels alkaloids.METHODS Centrifugal molding method was adopted in the preparation of soluble microneedles.With chondroitin sulfate consumption,PVP K120 consumption and 40%ethanol consumption as influencing factors,piercing rate as an evaluation index,the formulation was optimized by Box-Behnken response surface method,after which the morphology,piercing performance,drug content and in vitro transdermal performance were investigated.RESULTS The optimal formulation was determined to be 123 mg for chondroitin sulfate consumption,298 mg for PVP K120 consumption,and 2.4 mL for 40%ethanol consumption,the piercing rate was 98.3%.The soluble microneedles were yellow and square patch with conoid needle,which could pierce aluminum foil and rat skin,along with the drug content of(0.94±0.025)mg.The soluble microneedle group demonstrated the accumulative permeability rate of 91.4%within 24 h,which was higher than that in the gel ointment group,and the permeability accorded with Higuchi equation.CONCLUSION The soluble microneedles of A.brachypodum alkaloids exhibit good mechanical strength,which can achieve effective transdermal delivery of drugs.

Objective To study the effects of Ginkgo biloba extract(GBE)on the proliferation and apoptosis of human cerebral adventitia fibroblasts(HBVAFs)by regulating the phosphatidylinositol 3 kinase(PI3K)/protein kinase B(AKT)signaling pathway.Methods HBVAFs cells were divided into blank group(normal culture,no treatment),experimental-L,-M,-H groups(25,50 and 100 mg·L-1 GBE treatment for 24 h)and combined group(100 mg·L-1 GBE treatment and 2 nmol·L-1 insulin-like growth factor-1 treatment for 24 h).Cell proliferation was detected by thiazole blue assay,cell apoptosis was detected by flow cytometry,and the protein expressions of phosphorylated-PI3K(p-PI3K),PI3K、phosphorylated-AKT(p-AKT)and AKT were detected by Western blot.Results The cell survival rates of experimental-L,experimental-M,experimental-H,combined and blank groups were(66.78±8.21)％,(53.51±7.40)％,(42.33±6.01)％,(75.69±5.87)％and(96.77±12.80)％;the apoptosis rates were(24.83±2.47)％,(30.07±3.06)％,(37.02±4.66)％,(16.71±2.11)％and(8.99±0.19)％;p-PI3K/PI3K ratios were 0.75±0.07,0.62±0.06,0.43±0.04,0.72±0.05 and 0.90±0.09;p-AKT/AKT ratios were 0.70±0.07,0.60±0.06,0.38±0.03,0.69±0.06 and 0.90±0.09,respectively.The above indexes of the experimental-L,-M,-H groups were compared with the blank group,and the above indexes of the combined group were compared with the experimental-H group,the differences were statistically significant(all P＜0.05).Conclusion GBE can reduce the proliferation of HBVAFs,promote apoptosis,and its mechanism is related to the inhibition of PI3K/AKT signaling pathway.