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 understand the current status of discharge planning nursing for primipara who separated from their infants during hospitalization and provide a reference basis for constructing a clinical nursing plan.Methods:From February to June 2023, a field research about situation of nursing practice in discharge planning service among primiparas who separated from their infants was conducted in the Department of Obstetrics, Obstetrics and Gynecology Hospital Affiliated to Tongji University. Data was collected by field observation and informal interviews with 12 nurses and analyzed by three-level coding method of qualitative research.Results:All 12 nurses were female with 24-46 (33.33 ± 1.83) years old. The work content of the observation subjects could be divided into 4 items including providing infants′ health information, breastfeeding, postpartum rehabilitation, psychological care and social support. All the 4 items needed to be improved in providing infants′ health information, evaluating psychological status and social support, and quality of discharge teaching.Conclusions:It still needs further development in discharge planning nursing for primipara separated from their infants during hospitalization. It is urgent to improve the quality of discharge planning nursing for primiparas who have separated from their infants by developing scientific and standardized discharge planning nursing process, conducting standardized training for nurses, improving nurses′ psychosocial assessment ability, homogenizing health education, and improving humanistic care, so as to promote the rehabilitation of primiparas and get used to being a mother.

Objective:To observe the changes in the nutritional status of pediatric patients after allogeneic hematopoietic stem cell transplantation(allo-HSCT)for one year,and to analyze the risk factors.Methods:We collected data from 88 pediatric patients who underwent allo-HSCT at the Department of Hematology and Oncology in Children's Hospital of Nanjing Medical University between May 2018 and November 2022.All pediatric patients underwent nutritional status analysis before transplantation,at enrollment,3 months,6 months and 1 year after allo-HSCT.Linear regression model was used to analyze the risk factors for growth rate.Results:The body mass index Z score(BMI-Z)before allo-HSCT was(0.096±1.349),and decreased to(-0.258±1.438)、(-0.715±1.432)、(-0.584±1.444)at enrollment,3 months,6 months after allo-HSCT,and(-0.130±1.317)at 1 year after allo-HSCT(P<0.001).There was no significant change in BMI-Z between pre-transplantation and 1 year after transplantation(P=1.000).Height for age Z score(HAZ)before transplantation was(0.137±1.305)and decreased to(-0.083±1.267)、(-0.221±1.299)、(-0.269±1.282)in 3 months,6 months and 1 year after allo-HSCT(P<0.001).Multivariate linear regression showed that age≥10 years old(P=0.015)and chronic graft-versus-host disease(cGVHD)(P=0.005)were independent risk factors for change in HAZ.Conclusion:The BMI-Z of pediatric patients treated with allo-HSCT returned to the pre-transplantation level after one year,while HAZ continued to decrease.Allo-HSCT may cause impaired growth rate in pediatric patients.Attention should be paid to HAZ changes in pediatric patients before and after allo-HSCT,especially in pediatric patients≥10 years old of age and those with cGVHD.Effective nutritional intervention should be provided in time.

Objective To investigate the incidence rate,clinical characteristics,and prognosis of neonatal stroke in Shenzhen,China.Methods Led by Shenzhen Children's Hospital,the Shenzhen Neonatal Data Collaboration Network organized 21 institutions to collect 36 cases of neonatal stroke from January 2020 to December 2022.The incidence,clinical characteristics,treatment,and prognosis of neonatal stroke in Shenzhen were analyzed.Results The incidence rate of neonatal stroke in 21 hospitals from 2020 to 2022 was 1/15 137,1/6 060,and 1/7 704,respectively.Ischemic stroke accounted for 75％(27/36);boys accounted for 64％(23/36).Among the 36 neonates,31(86％)had disease onset within 3 days after birth,and 19(53％)had convulsion as the initial presentation.Cerebral MRI showed that 22 neonates(61％)had left cerebral infarction and 13(36％)had basal ganglia infarction.Magnetic resonance angiography was performed for 12 neonates,among whom 9(75％)had involvement of the middle cerebral artery.Electroencephalography was performed for 29 neonates,with sharp waves in 21 neonates(72％)and seizures in 10 neonates(34％).Symptomatic/supportive treatment varied across different hospitals.Neonatal Behavioral Neurological Assessment was performed for 12 neonates(33％,12/36),with a mean score of(32±4)points.The prognosis of 27 neonates was followed up to around 12 months of age,with 44％(12/27)of the neonates having a good prognosis.Conclusions Ischemic stroke is the main type of neonatal stroke,often with convulsions as the initial presentation,involvement of the middle cerebral artery,sharp waves on electroencephalography,and a relatively low neurodevelopment score.Symptomatic/supportive treatment is the main treatment method,and some neonates tend to have a poor prognosis.

Objective: To evaluate different methods' efficacy of controlling acute bleeding and managing long-term menstruation in patients with heavy menstrual bleeding (HMB) associated with antithrombotic therapy. Methods: The clinical data of 22 cases with HMB associated with antithrombotic therapy admitted to Peking University People's Hospital from January 2010 to August 2022 were analyzed, aged 39 years old (26-46 years). Changes in menstrual volume, hemoglobin (Hb), and quality of life were collected after control of acute bleeding and long-term menstrual management. Menstrual volume was assessed by pictorial blood assessment chart (PBAC), and quality of life was assessed by menorrhagia multi-attribute scale (MMAS). Results: (1) Treatment of acute bleeding: of the 22 cases with HMB associated with antithrombotic therapy, 16 cases were treated in our hospital and 6 in other hospital for emergency bleeding; of the 16 cases treated in our hospital, 3 underwent emergency intrauterine Foley catheter balloon compression due to severe bleeding (Hb decreased by 20 to 40 g/L within 12 hours). Of the 22 cases with antithrombotic therapy-related HMB, 15 (including 2 cases with severe bleeding) underwent emergency aspiration or endometrial resection, and intraoperative placement of levonorgestrel-releasing intrauterine system (LNG-IUS) followed by a significant reduction in bleeding volume; 3 cases had controlled acute bleeding after rivaroxaban dose reduction and continued observation; 2 cases were given gonadotropin-releasing hormone agonists to control acute bleeding in other hospital, of which 1 case was temporarily treated with periodic blood transfusion, and the other one patient underwent total hysterectomy; and 2 cases had temporary amenorrhea with oral mifepristone after intrauterine balloon compression or oral norethindrone. (2) Long-term menstrual management: of the 22 cases with antithrombotic therapy-related HMB, 15 had LNG-IUS placement and 12 had LNG-IUS placement for 6 months, and menstrual volume was significantly reduced [PBAC scores were 365.0 (272.5-460.0) vs 25.0 (12.5-37.5), respectively; Z=4.593, P<0.001], Hb was significantly increased [91.5 g/L (71.8-108.2 g/L) vs 128.5 g/L (121.2-142.5 g/L); Z=4.695, P<0.001], and quality of life was significantly improved [MMAS scores were 415.0 (327.5-472.5) vs 580.0 (570.0-580.0), respectively; Z=-3.062, P=0.002] before placement compared with 6 months after placement. Three rivaroxaban dose reduction patients' PBAC scores decreased by 20 to 35 but remained >100, and perceived quality of life did not change significantly. Two cases with temporary amenorrhea treated with oral mifepristone felt significantly improved quality of life, and the MMAS scores increased by 220 and 180, respectively. Conclusion: Intrauterine Foley catheter balloon compression, aspiration or endometrial ablation could be used to control acute bleeding in patients with antithrombotic therapy-related HMB, and LNG-IUS for long-term management could reduce menstrual volume, increase hemoglobin, and improve the quality of life of patients.
Female ; Humans ; Adult ; Menorrhagia/etiology* ; Fibrinolytic Agents/adverse effects* ; Levonorgestrel/adverse effects* ; Amenorrhea/drug therapy* ; Mifepristone/therapeutic use* ; Quality of Life ; Rivaroxaban/therapeutic use* ; Hemoglobins ; Intrauterine Devices, Medicated/adverse effects* ; Contraceptive Agents, Female

AIM: To investigate the differences in visual recovery, corneal astigmatism, and rotation stability of Toric intraocular lens(TIOL)implantation in cataract patients with different axial lengths.METHODS: Retrospective analysis. A total of 132 patients(132 eyes)with age-related cataract and corneal astigmatism who underwent phacoemulsification cataract extraction combined with TIOL implantation in our hospital's ophthalmology department from February 2021 to September 2022 were selected. They were divided into two groups based on the axial length: the group with axial length ≤24mm(79 cases, 79 eyes)and the group with axial length >24mm(53 cases, 53 eyes). Compare the best corrected distance visual acuity(BCDVA), corneal astigmatism, and TIOL rotation between the two groups of patients at 3mo after surgery.RESULT: After 3mo of surgery, both groups of patients had improved BCDVA and significantly decreased corneal astigmatism compared to those before surgery(P<0.001). However, there was no difference in BCDVA and corneal astigmatism between the two groups(P>0.05), and there was no significant difference in TIOL rotation between the two groups [(5.24±3.72)° vs.(6.36±4.21)°, P=0.110].CONCLUSION: There is no significant difference in visual recovery, corneal astigmatism, and TIOL rotational stability after TIOL implantation in cataract patients with different axial lengths.

The effective components of flavonoids in the "Pueraria lobata-Hovenia dulcis" drug pair have low bioavailability in vivo due to their unstable characteristics. This study used microemulsions with amphoteric carrier properties to solve this problem. The study drew pseudo-ternary phase diagrams through titration compatibility experiments of the oil phase with emulsifiers and co-emulsifiers and screened the prescription composition of blank microemulsions. The study used average particle size and PDI as evaluation indicators, and the central composite design-response surface method(CCD-RSM) was used to optimize the prescription; high-dosage drug-loaded microemulsions were obtained, and their physicochemical properties, appearance, and stability were evaluated. The results showed that when ethyl butyrate was used as the oil phase, polysorbate 80(tween 80) as the surfactant, and anhydrous ethanol as the cosurfactant, the maximum microemulsion area was obtained. When the difference in results was small, K_(m )of 1∶4 was chosen to ensure the safety of the prescription. The prescription composition optimized by the CCD-RSM was ethyl butyrate(16.28%), tween 80(9.59%), and anhydrous ethanol(38.34%). When the dosage reached 3% of the system mass, the total flavonoid microemulsion prepared had a clear and transparent appearance, with average particle size, PDI, and potential of(74.25±1.58)nm, 0.277±0.043, and(-0.08±0.07) mV, respectively. The microemulsion was spherical and evenly distributed under transmission electron microscopy. The centrifugal stability and temperature stability were good, and there was no layering or demulsification phenomenon, which significantly improved the in vitro dissolution of total flavonoids.
Polysorbates/chemistry* ; Flavonoids ; Pueraria ; Surface-Active Agents/chemistry* ; Ethanol ; Emulsions ; Particle Size ; Solubility

The Baimai Ointment with the effect of relaxing sinew and activating collaterals demonstrates a definite effect on Baimai disease with pain, spasm, stiffness and other symptoms, while the pharmacodynamic characteristics and mechanism of this agent remain unclear. In this study, a rat model of chronic compression of L4 dorsal root ganglion(CCD) was established by lumbar disc herniation, and the efficacy and mechanism of Baimai Ointment in the treatment of CCD were preliminarily explored by behavioral tests, side effect evaluation, network analysis, antagonist and molecular biology verification. The pharmacodynamic experiment indicated that Baimai Ointment significantly improved the pain thresholds(mechanical pain, thermal pain, and cold pain) and gait behavior of CCD model rats without causing tolerance or obvious toxic and side effects. Baimai Ointment inhibited the second-phase nociceptive response of mice in the formalin test, increased the hot plate threshold of normal mice, and down-regulated the expression of inflammatory cytokines in the spinal cord. Network analysis showed that Baimai Ointment had synergistic effect in the treatment of CCD and was related to descending inhibition/facilitation system and neuroinflammation. Furthermore, behavioral tests, Western blot, and immunofluorescence assay revealed that the pain-relieving effect of Baimai Ointment on CCD may be related to the regulation of the interaction between neuroactive ligand and receptors(neuroligands) such as CHRNA7, ADRA2A, and ADRB2, and the down-regulation of the expression of NOS2/pERK/PI3K, the core regulatory element of HIF-1 signaling pathway in spinal microglia. The findings preliminarily reveal the mechanism of relaxing sinew and activating collaterals of Baimai Ointment in the treatment of Baimai disease, providing a reference for the rational drug use and further research of this agent.
Rats ; Mice ; Animals ; Chronic Pain/metabolism* ; Rats, Sprague-Dawley ; Ganglia, Spinal/metabolism* ; Ligands ; Signal Transduction ; Hyperalgesia/metabolism* ; Drugs, Chinese Herbal

Objective:To investigate the clinical characteristics of circadian rhythm disorder of blood pressure and its impact on orthostatic hypotension (OH) in Parkinson′s disease (PD).Methods:A total of 165 PD patients from Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine from August 2019 to October 2021 were consecutively enrolled. Medical history and scores of motor and non-motor symptoms of patients were collected. Twenty-four-hour ambulatory blood pressure and OH data were collected, and the OH questionnaire was completed. The incidence of each type of circadian rhythm disorder of blood pressure was investigated. The t test, chi-square test and Mann-Whitney U test were used to determine between-group differences of circadian rhythm disorder of blood pressure. The linear trends in clinical characteristics were tested by linear regression analysis. Logistic regression analysis was used to analyze the relationship between different circadian rhythm disorders of blood pressure and OH as well as symptomatic OH (SOH). Results:In 165 PD patients, the incidence of reverse dipping pattern was 39.39% (65/165), nocturnal hypertension was 43.64% (72/165), and awakening hypotension was 31.52% (52/165). Compared with patients without reverse dipping pattern, patients with reverse dipping pattern were older [(71.72±7.81) years vs (65.29±9.68) years, t=-4.491, P<0.001], had later onset age [(66.67±9.10) years vs (62.16±10.66) years, t=-2.809, P=0.006], longer duration [36.00(20.50, 95.50) months vs 24.00(12.00, 41.75) months, Z=-3.393, P<0.001], higher dose of levodopa (LD) [(426.15±267.38) mg/d vs (284.00±235.58) mg/d, t=-3.590, P<0.001], higher levodopa equivalent dose (LED) [(514.80±360.03) mg/d vs (341.44±284.57) mg/d, t=-3.440, P=0.001], higher Unified Parkinson′s Disease Rating Scale (UPDRS)-Ⅱ scores (12.92±6.38 vs 9.54±5.59, t=-3.434, P=0.001), higher UPDRS-Ⅲ scores (28.34±11.60 vs 21.41±12.18, t=-3.508, P=0.001) and higher percentages of hallucinations [18.46% (12/65) vs 7.00% (7/100), χ2 =5.079, P=0.024]. Compared with patients without awakening hypotension, patients with awakening hypotension were older [(70.83±7.09) years vs (66.44±10.16) years, t=-2.811, P=0.006]. Compared with patients without nocturnal hypertension, patients with nocturnal hypertension had longer duration [39.50(15.00, 96.00) months vs 24.00 (12.00, 36.00) months, Z=-2.944, P=0.003], higher LD [(398.61±251.19) mg/d vs (294.62±254.25) mg/d, t=-2.619, P=0.010], higher LED [(493.28±344.02) mg/d vs (345.05±298.59) mg/d, t=-2.959, P=0.004], higher percentages of hallucinations [19.44% (14/72) vs 5.38% (5/93), χ2 =7.882, P=0.005], higher UPDRS-Ⅱ scores (12.08±6.33 vs 10.00±5.86, t=-2.086, P=0.039), higher UPDRS-Ⅲ scores (26.50±11.72 vs 22.42±12.66, t=-2.034, P=0.044), and greater blood pressure variability (BPV) (20.66±5.47 vs 17.44±5.36, t=-3.798, P<0.001). Trend analysis showed that the variety of circadian rhythm was positively correlated with age and duration, use of levodopa and monoamine oxidase B inhibitors and amantidine, morning and daily LD and LED, UPDRS-Ⅱ, UPDRS-Ⅲ and Hamilton Anxiety Scale scores, hallucinations, OH and SOH, and BPV in PD ( P<0.05). Multivariate Logistic regression analysis showed that awakening hypotension ( OR=3.35, 95% CI 1.55-7.22, P=0.002) and nocturnal hypertension ( OR=2.44, 95% CI 1.20-4.97, P=0.014) were risk factors for OH, and LED ( OR=1.21, 95% CI 1.01-1.43, P=0.035), UPDRS-Ⅲ scores ( OR=1.09, 95% CI 1.02-1.16, P=0.009) and w-BPV ( OR=1.14, 95% CI 1.01-1.29, P=0.029) were independent risk factors for SOH. Conclusions:Circadian rhythm disorder of blood pressure was correlated with age, duration, severity of motor symptoms. Awakening hypotension and nocturnal hypertension are independent risk factors for OH in PD.

BACKGROUND: Growth differentiation factor 15 (GDF-15) has been explored as a potential biomarker for various inflammatory diseases and cardiovascular events. This study aimed to assess the predictive role of GDF-15 levels in cardiovascular events and all-cause mortality, considering traditional risk factors and other biomarkers. METHODS: A prospective study was conducted and 3699 patients with stable coronary artery disease (CAD) were enrolled into the research. Baseline GDF-15 levels were measured. Median follow-up was 3.1 years during the study. We analyzed clinical variables and several biomarkers. Multivariable Cox regression analysis was performed to evaluate prognostic performance of GDF-15 levels in predicting myocardial infarction (MI), heart failure, stroke, cardiovascular death, and non-cardiovascular death. RESULTS: Baseline GDF-15 levels for 3699 patients were grouped by quartile (≤ 1153, 1153-1888, 1888-3043, > 3043 ng/L). Higher GDF-15 levels were associated with older age, male gender, history of hypertension, and elevated levels of N-terminal pro B-type natriuretic peptide (NT-pro BNP), soluble suppression of tumorigenesis-2 (sST2), and creatine (each with P < 0.001). Adjusting for established risk factors and biomarkers in Cox proportional hazards models, a 1 standard deviation (SD) increase in GDF-15 was associated with elevated risk of clinical events [hazard ratio (HR) = 2.18, 95% confidence interval (CI): (1.52-3.11)], including: MI [HR = 2.83 95% CI: (1.03-7.74)], heart failure [HR = 2.71 95% CI: (1.18-6.23)], cardiovascular and non-cardiovascular death [HR = 2.48, 95% CI (1.49-4.11)] during the median follow up of 3.1 years. CONCLUSIONS Higher levels of GDF-15 consistently provides prognostic information for cardiovascular events and all cause death, independent of clinical risk factors and other biomarkers. GDF-15 could be considered as a valuable addition to future risk prediction model in secondary prevention for predicting clinical events in patient with stable CAD.