OBJECTIVES: To study the effect of prophylactic phenytoin (PHT) or levetiracetam (LEV) on busulfan (BU) blood concentration in children undergoing hematopoietic stem cell transplantation. METHODS: Pediatric patients conditioned with BU plus cyclophosphamide and fludarabine at the First People's Hospital of Chenzhou from September 2023 to February 2025 were retrospectively included. Patients were grouped by prophylactic antiepileptic regimen into PHT (n=24) and LEV (n=26). BU blood concentrations at the end of infusion (0 hour) and at 1, 2, and 4 hours post-infusion were compared between groups. RESULTS: At 0 hour post-infusion, BU blood concentrations did not differ significantly between groups (P>0.05). At 1, 2, and 4 hours post-infusion, BU blood concentrations were higher in the LEV group than in the PHT group (P<0.05). The area under the concentration-time curve from 0 to ∞ (AUC_0-∞) was greater in the LEV group (P<0.001), and the attainment rate of AUC_0-∞ was higher in the LEV group than in the PHT group (73% vs 21%, P<0.001). No significant differences were observed between groups in time to hematopoietic engraftment or in the incidence of BU-related adverse drug reactions (P>0.05). CONCLUSIONS Compared with PHT, LEV prophylaxis is associated with higher BU blood concentration and a higher AUC_0-∞ attainment rate. There is no observed difference in BU efficacy or safety between PHT and LEV.
Humans ; Levetiracetam/therapeutic use* ; Busulfan/pharmacokinetics* ; Hematopoietic Stem Cell Transplantation ; Male ; Female ; Child ; Child, Preschool ; Phenytoin/pharmacology* ; Infant ; Retrospective Studies ; Anticonvulsants/pharmacology* ; Adolescent

BACKGROUND: China is seeing a growing demand for rehabilitation treatments for post-stroke upper limb spastic paresis (PSSP-UL). Although acupuncture is known to be effective for PSSP-UL, there is room to enhance its efficacy. OBJECTIVE: This study explored a semi-personalized acupuncture approach for PSSP-UL that used three-dimensional kinematic analysis (3DKA) results to select additional acupoints, and investigated the feasibility, efficacy and safety of this approach. DESIGN, SETTING, PARTICIPANTS AND INTERVENTIONS: This single-blind, single-center, randomized, controlled trial involved 74 participants who experienced a first-ever ischemic or hemorrhagic stroke with spastic upper limb paresis. The participants were then randomly assigned to the intervention group or the control group in a 1:1 ratio. Both groups received conventional treatments and acupuncture treatment 5 days a week for 4 weeks. The main acupoints in both groups were the same, while participants in the intervention group received additional acupoints selected on the basis of 3DKA results. Follow-up assessments were conducted for 8 weeks after the treatment. MAIN OUTCOME MEASURES: The primary outcome was the Fugl-Meyer Assessment for Upper Extremity (FMA-UE) response rate (≥ 6-point change) at week 4. Secondary outcomes included changes in motor function (FMA-UE), Brunnstrom recovery stage (BRS), manual muscle test (MMT), spasticity (Modified Ashworth Scale, MAS), and activities of daily life (Modified Barthel Index, MBI) at week 4 and week 12. RESULTS: Sixty-four participants completed the trial and underwent analyses. Compared with control group, the intervention group exhibited a significantly higher FMA-UE response rate at week 4 (χ² = 5.479, P = 0.019) and greater improvements in FMA-UE at both week 4 and week 12 (both P < 0.001). The intervention group also showed bigger improvements from baseline in the MMT grades for shoulder adduction and elbow flexion at weeks 4 and 12 as well as thumb adduction at week 4 (P = 0.007, P = 0.049, P = 0.019, P = 0.008, P = 0.029, respectively). The intervention group showed a better change in the MBI at both week 4 and week 12 (P = 0.004 and P = 0.010, respectively). Although the intervention group had a higher BRS for the hand at week 12 (P = 0.041), no intergroup differences were observed at week 4 (all P > 0.05). The two groups showed no differences in MAS grades as well as in BRS for the arm at weeks 4 and 12 (all P > 0.05). CONCLUSION: Semi-personalized acupuncture prescription based on 3DKA results significantly improved motor function, muscle strength, and activities of daily living in patients with PSSP-UL. TRIAL REGISTRATION Chinese Clinical Trial Registry ChiCTR2200056216. Please cite this article as: Huang XY, Liao OP, Jiang SY, Tao JM, Li Y, Lu XY, Li YY, Wang C, Li J, Ma XP. Three-dimensional kinematic analysis can improve the efficacy of acupoint selection for post-stroke patients with upper limb spastic paresis: A randomized controlled trial. J Integr Med. 2025; 23(1): 15-24.
Humans ; Male ; Female ; Middle Aged ; Acupuncture Points ; Upper Extremity/physiopathology* ; Biomechanical Phenomena ; Single-Blind Method ; Aged ; Stroke/therapy* ; Acupuncture Therapy/methods* ; Stroke Rehabilitation/methods* ; Adult ; Muscle Spasticity/therapy* ; Paresis/physiopathology* ; Treatment Outcome

Objective To compare the pharmaceutics and drug interactions of noiiglutide injection,INS068 injection,HR17031 Injection,and noiiglutide+INS068 injection in healthy subjects Methods This was a single center,randomized,open-label,4-cycle,4-cohort trial.Healthy subjects were allocated to 4 groups randomly.HR17031(17 U/0.04 mg),INS068(17 U),noliglycopeptide(0.04 mg),and INS068(17 U)combined with noiiglutide(0.04 mg)were injected subcutaneously into the abdomenon on day 1,8,15 and 22 respectively.Venous blood was collected at different timing before and after administration,and the concentrations of noiiglutide in plasma and INS068 in serum were measured by HPLC-MS/MS method.Relevant pharmacokinetic parameters were calculated using the WinNonlin non compartment model.Results In HR17031,INS068,and INS068 combined with noiiglutide groups,the main pharmacokinetic parameters of INS068 in serum were calculated and listed as follows:Cmax were(19.50±4.06),(18.10±4.56)and(18.40±5.81)ng·mL-1,tmax was 12,10 and 8 h,t1/2 was(9.27±1.70),(11.00±2.81)and(11.0±3.18)h,AUC0-twere(505.00±62.20),(498.00±70.50)and(491.00±74.20)ng·mL-1·h.In HR17031,noiiglutide,and INS068 combined with noiiglutide groups,the main pharmacokinetic parameters of noiiglutide in plasma were calculated and listed as follows:Cmax were(3.61±0.82),(4.63±0.87)and(4.54±0.86)ng·mL-1,tmax was all 8.00 h,t1/2 was(10.50±1.61),(9.49±1.40)and(9.55±1.61)h,AUC0-twere(94.30±20.10),(106.00±20.20)and(105.00±19.00)ng·mL-1·h.Conclusion There was no significant difference in bioavailability of INS068 and noiiglutide in HR17031 compared with INS068 and noiiglutide whether combined or used alone.

Objective: To investigate the clinical and pathological features of primary gastric (gastrointestinal)-type mucoglandular lesions of the endometrium. Methods: Eight cases of primary gastric (gastrointestinal)-type mucoglandular lesions of endometrium diagnosed between 2014 to 2022 were retrieved from pathology archives of the Obstetrics and Gynecology Hospital Affiliated to Fudan University, Shanghai, China. The clinical history, pathological sections and follow-ups were analyzed. Results: The eight patients ranged in age from 35 to 67 years, with an average age of 55.5 years. Seven patients were examined for high-risk human papillary virus (HPV) before operation. Only one of them was positive for high-risk HPV52. No cervical mucinous lesions were found in any of the patients. Two cases were invasive gastric (gastrointestinal)-type adenocarcinoma, 2 cases were benign gastric (gastrointestinal)-type mucinous metaplasia, and the other 4 cases were atypical gastric (gastrointestinal)-type mucinous gland hyperplasia. Microscopically, tumor cells showed mucous epithelium with gastrointestinal differentiation. Immunophenotyping showed that MUC6 was diffusely or focally positive in 5 cases, CK20 and CDX2 were positive in 3 cases. And p16 was negative or focally positive in 5 cases and strongly positive in 1 case. ER was expressed in both benign and atypical lesions, and weakly positive or negative in the invasive adenocarcinoma. p53 showed mutant expression in one case and wild-type expression in the rest. HPV in situ hybridization was negative. Conclusions: Primary gastric (gastrointestinal)-type mucoglandular lesions of the endometrium show various forms of gastrointestinal differentiation, which are high-risk HPV independent. Morphology combined with immunohistochemistry is helpful for the diagnosis, which can only be made on exclusion of cervical gastrointestinal glandular lesion, gastrointestinal metastatic carcinoma and the mucinous subtype of endometrioid carcinoma.
Female ; Humans ; Middle Aged ; Adult ; Aged ; Uterine Cervical Neoplasms/pathology* ; Papillomavirus Infections ; China ; Adenocarcinoma/pathology* ; Endometrium/pathology* ; Gastrointestinal Neoplasms/pathology* ; Biomarkers, Tumor/analysis*

BACKGROUND: Clinical outcomes are poor if patients with acute heart failure (AHF) are discharged with residual congestion in the presence of renal dysfunction. However, there is no single indication to reflect the combined effects of the two related pathophysiological processes. We, therefore, proposed an indicator, congestion and renal index (CRI), and examined the associations between the CRI and one-year outcomes and the incremental prognostic value of CRI compared with the established scoring systems in a multicenter prospective cohort of AHF. METHODS: We enrolled AHF patients and calculated the ratio of thoracic fluid content index divided by estimated glomerular filtration rate before discharge, as CRI. Then we examined the associations between CRI and one-year outcomes. RESULTS: A total of 944 patients were included in the analysis (mean age 63.3 ± 13.8 years, 39.3% women). Compared with patients with CRI ≤ 0.59 mL/min per kΩ, those with CRI > 0.59 mL/min per kΩ had higher risks of cardiovascular death or HF hospitalization (HR = 1.56 [1.13-2.15]) and all-cause death or all-cause hospitalization (HR = 1.33 [1.01-1.74]). CRI had an incremental prognostic value compared with the established scoring system. CONCLUSIONS In patients with AHF, CRI is independently associated with the risk of death or hospitalization within one year, and improves the risk stratification of the established risk models.

OBJECTIVE: To derive the Chinese medicine (CM) syndrome classification and subgroup syndrome characteristics of ischemic stroke patients. METHODS: By extracting the CM clinical electronic medical records (EMRs) of 7,170 hospitalized patients with ischemic stroke from 2016 to 2018 at Weifang Hospital of Traditional Chinese Medicine, Shandong Province, China, a patient similarity network (PSN) was constructed based on the symptomatic phenotype of the patients. Thereafter the efficient community detection method BGLL was used to identify subgroups of patients. Finally, subgroups with a large number of cases were selected to analyze the specific manifestations of clinical symptoms and CM syndromes in each subgroup. RESULTS: Seven main subgroups of patients with specific symptom characteristics were identified, including M3, M2, M1, M5, M0, M29 and M4. M3 and M0 subgroups had prominent posterior circulatory symptoms, while M3 was associated with autonomic disorders, and M4 manifested as anxiety; M2 and M4 had motor and motor coordination disorders; M1 had sensory disorders; M5 had more obvious lung infections; M29 had a disorder of consciousness. The specificity of CM syndromes of each subgroup was as follows. M3, M2, M1, M0, M29 and M4 all had the same syndrome as wind phlegm pattern; M3 and M0 both showed hyperactivity of Gan (Liver) yang pattern; M2 and M29 had similar syndromes, which corresponded to intertwined phlegm and blood stasis pattern and phlegm-stasis obstructing meridians pattern, respectively. The manifestations of CM syndromes often appeared in a combination of 2 or more syndrome elements. The most common combination of these 7 subgroups was wind-phlegm. The 7 subgroups of CM syndrome elements were specifically manifested as pathogenic wind, pathogenic phlegm, and deficiency pathogens. CONCLUSIONS There were 7 main symptom similarity-based subgroups in ischemic stroke patients, and their specific characteristics were obvious. The main syndromes were wind phlegm pattern and hyperactivity of Gan yang pattern.
Humans ; Syndrome ; Ischemic Stroke ; Medicine, Chinese Traditional ; Liver ; Phenotype

The development of chemoresistance which results in a poor prognosis often renders current treatments for colorectal cancer(CRC).In this study,we identified reduced microvessel density(MVD)and vascular immaturity resulting from endothelial apoptosis as therapeutic targets for overcoming chemoresistance.We focused on the effect of metformin on MVD,vascular maturity,and endothelial apoptosis of CRCs with a non-angiogenic phenotype,and further investigated its effect in overcoming chemoresistance.In situ transplanted cancer models were established to compare MVD,endothelial apoptosis and vascular maturity,and function in tumors from metformin-and vehicle-treated mice.An in vitro co-culture system was used to observe the effects of metformin on tumor cell-induced endothelial apoptosis.Transcriptome sequencing was performed for genetic screening.Non-angiogenic CRC developed inde-pendently of angiogenesis and was characterized by vascular leakage,immaturity,reduced MVD,and non-hypoxia.This phenomenon had also been observed in human CRC.Furthermore,non-angiogenic CRCs showed a worse response to chemotherapeutic drugs in vivo than in vitro.By suppressing endo-thelial apoptosis,metformin sensitized non-angiogenic CRCs to chemo-drugs via elevation of MVD and improvement of vascular maturity.Further results showed that endothelial apoptosis was induced by tumor cells via activation of caspase signaling,which was abrogated by metformin administration.These findings provide pre-clinical evidence for the involvement of endothelial apoptosis and subsequent vascular immaturity in the chemoresistance of non-angiogenic CRC.By suppressing endothelial apoptosis,metformin restores vascular maturity and function and sensitizes CRC to chemotherapeutic drugs via a vascular mechanism.

Aim To study the effect of different hepa- ry.Methods First, heparin derivatives with different rin sulfation patterns on bleomycin induced lung inju- sulfation patterns,6-desulfated heparin (6-DeH) and N-acetvlated heparin ( N-AcH ) , were synthesized.Secondly, the effect of these compounds on BLM-in¬duced bronchial epithelial cell ( BEARS-2B) injury was evaluated via lactate dehydrogenase activity, MTT experiment, Annexin V/ PI staining and Hoechst 33258 staining.Then , immunofluorescence staining and West¬ern blotting were used to investigate the shedding of Svndecan-1 and the activation of c-Met by 6-DeH/Akt j j signaling pathway.Finally, a BLM-induced lung injury mouse model was used to further verify the protective effect of 6-DeH by HE staining, Svndecan-1 immunos- taining,bodv weight change,and survival rate.Results In the BLM-induced BEARS-2B injury model, 6- DeH was selected as the best candidate, which exerted their effect by competitively binding to BLM, thereby reducing the damage of heparan sulfate barrier (Svnde- can-1 ) on cell surface, and improving cell survival by activating the downstream c-Met/Akt pathway.In the BLM-induced lung injury mouse model, it was further confirmed that 6-DeH reduced the shedding of Svnde- can-1 in the early stage, and delayed the lung injury and fibrosis process.Conclusions 6-DeH protects the bronchial epithelial cells against BLM-induced lung in¬jur)' through inhibiting the shedding of Svndecan-1 and activating the c-Met/Akt signaling pathway.

OBJECTIVES: To examine the association between duration of fever before intravenous immunoglobulin (IVIG) treatment and IVIG resistance in children with Kawasaki disease (KD). METHODS: A retrospective analysis was performed on the medical data of 317 children with KD who were admitted from January 2018 to December 2020. According to the duration of fever before IVIG treatment, they were divided into two groups: short fever duration group (≤4 days) with 92 children and long fever duration group (>4 days) with 225 children. According to the presence or absence of IVIG resistance, each group was further divided into a drug-resistance group and a non-drug-resistance group. Baseline data and laboratory results were compared between groups. A multivariate logistic regression analysis was used to identify the influencing factors for IVIG resistance. RESULTS: In the short fever duration group, 19 children (20.7%) had IVIG resistance and 5 children (5.4%) had coronary artery aneurysm, and in the long fever duration group, 22 children (9.8%) had IVIG resistance and 19 children (8.4%) had coronary artery aneurysm, suggesting that the short fever duration group had a significantly higher rate of IVIG resistance than the long fever duration group (P<0.05), while there was no significant difference in the incidence rate of coronary artery aneurysm between the two groups (P>0.05). In the short fever duration group, compared with the children without drug resistance, the children with drug resistance had a significantly lower level of blood sodium and significantly higher levels of procalcitonin, C-reactive protein, and N-terminal B-type natriuretic peptide before treatment (P<0.05). In the long fever duration group, the children with drug resistance had significantly lower levels of blood sodium and creatine kinase before treatment than those without drug resistance (P<0.05). The multivariate logistic regression analysis showed that a reduction in blood sodium level was associated with IVIG resistance in the long fever duration group (P<0.05). CONCLUSIONS IVIG resistance in children with KD varies with the duration of fever before treatment. A reduction in blood sodium is associated with IVIG resistance in KD children with a duration of fever of >4 days before treatment.
Child ; Coronary Aneurysm/drug therapy* ; Fever/etiology* ; Humans ; Immunoglobulins, Intravenous/therapeutic use* ; Infant ; Mucocutaneous Lymph Node Syndrome/drug therapy* ; Retrospective Studies ; Sodium/therapeutic use*

Objective: To investigate the incidence and trend of short-term outcomes among preterm infants born <34 weeks' gestation. Methods: A secondary analysis of data from the standardized database established by a multicenter cluster-randomized controlled study "reduction of infection in neonatal intensive care units (NICU) using the evidence-based practice for improving quality (REIN-EPIQ) study". This study was conducted in 25 tertiary NICU. A total of 27 192 infants with gestational age <34 weeks at birth and admitted to NICU within the first 7 days of life from May 2015 to April 2018 were enrolled. Infants with severe congenital malformation were excluded. Descriptive analyses were used to describe the mortality and major morbidities of preterm infants by gestational age groups and different admission year groups. Cochran-Armitage test and Jonckheere-Terpstra test were used to analyze the trend of incidences of mortality and morbidities in 3 study-years. Multiple Logistic regression model was constructed to analyze the differences of outcomes in 3 study-years adjusting for confounders. Results: A total of 27 192 preterm infants were enrolled with gestational age of (31.3±2.0) weeks at birth and weight of (1 617±415) g at birth. Overall, 9.5% (2 594/27 192) of infants were discharged against medical advice, and the overall mortality rate was 10.7% (2 907/27 192). Mortality for infants who received complete care was 4.7% (1 147/24 598), and mortality or any major morbidity was 26.2% (6 452/24 598). The incidences of moderate to severe bronchopulmonary dysplasia, sepsis, severe intraventricular hemorrhage or periventricular leukomalacia, proven necrotizing enterocolitis, and severe retinopathy of prematurity were 16.0% (4 342/27 192), 11.9% (3 225/27 192), 6.8% (1 641/24 206), 3.6% (939/25 762) and 1.5% (214/13 868), respectively. There was a decreasing of the overall mortality (P<0.001) during the 3 years. Also, the incidences for sepsis and severe retinopathy of prematurity both decreased (both P<0.001). However, there were no significant differences in the major morbidity in preterm infants who received complete care during the 3-year study period (P=0.230). After adjusting for confounders, infants admitted during the third study year showed significantly lower risk of overall mortality (adjust OR=0.62, 95%CI 0.55-0.69, P<0.001), mortality or major morbidity, moderate to severe bronchopulmonary dysplasia, sepsis and severe retinopathy of prematurity, compared to those admitted in the first study year (all P<0.05). Conclusions: From 2015 to 2018, the mortality and major morbidities among preterm infants in Chinese NICU decreased, but there is still space for further efforts. Further targeted quality improvement is needed to improve the overall outcome of preterm infants.
Bronchopulmonary Dysplasia/epidemiology* ; Gestational Age ; Humans ; Infant ; Infant Mortality/trends* ; Infant, Newborn ; Infant, Premature ; Infant, Premature, Diseases/epidemiology* ; Patient Discharge ; Retinopathy of Prematurity/epidemiology* ; Sepsis/epidemiology*