OBJECTIVES: To evaluate the safety and efficacy of thiotepa (TT)-containing conditioning regimens for allogeneic hematopoietic stem cell transplantation (HSCT) in children with inborn errors of immunity (IEI). METHODS: Clinical data of 22 children with IEI who underwent HSCT were retrospectively reviewed. Survival after HSCT was estimated using the Kaplan-Meier method. RESULTS: Nine patients received a traditional conditioning regimen (fludarabine + busulfan + cyclophosphamide/etoposide) and underwent peripheral blood stem cell transplantation (PBSCT). Thirteen patients received a TT-containing modified conditioning regimen (TT + fludarabine + busulfan + cyclophosphamide), including seven PBSCT and six umbilical cord blood transplantation (UCBT) cases. Successful engraftment with complete donor chimerism was achieved in all patients. Acute graft-versus-host disease occurred in 12 patients (one with grade III and the remaining with grade I-II). Chronic graft-versus-host disease occurred in one patient. The incidence of EB viremia in UCBT patients was lower than that in PBSCT patients (P<0.05). Over a median follow-up of 36.0 months, one death occurred. The 3-year overall survival (OS) rate was 100% for the modified regimen and 88.9% ± 10.5% for the traditional regimen (P=0.229). When comparing transplantation types, the 3-year OS rates were 100% for UCBT and 93.8% ± 6.1% for PBSCT (P>0.05), and the 3-year event-free survival rates were 100% and 87.1% ± 8.6%, respectively (P>0.05). CONCLUSIONS TT-containing conditioning for allogeneic HSCT in children with IEI is safe and effective. Both UCBT and PBSCT may achieve high success rates.
Humans ; Retrospective Studies ; Transplantation Conditioning/methods* ; Thiotepa/therapeutic use* ; Hematopoietic Stem Cell Transplantation/adverse effects* ; Male ; Female ; Child, Preschool ; Infant ; Child ; Transplantation, Homologous ; Graft vs Host Disease ; Adolescent

OBJECTIVE: To explore the therapeutic effects and underlying mechanisms of Dendrobium officinale (Tiepi Shihu) extract (DOE) on insomnia. METHODS: Forty-two male Sprague-Dawley rats were randomly divided into 6 groups (n=7 per group): normal control, model control, melatonin (MT, 40 mg/kg), and 3-dose DOE (0.25, 0.50, and 1.00 g/kg) groups. Rats were raised in a strong-light (10,000 LUX) and -noise (>80 db) environment (12 h/d) for 16 weeks to induce insomnia, and from week 10 to week 16, MT and DOE were correspondingly administered to rats. The behavior tests including sodium pentobarbital-induced sleep experiment, sucrose preference test, and autonomous activity test were used to evaluate changes in sleep and emotions of rats. The metabolic-related indicators such as blood pressure, blood viscosity, blood glucose, and uric acid in rats were measured. The pathological changes in the cornu ammonis 1 (CA1) region of rat brain were evaluated using hematoxylin and eosin staining and Nissl staining. Additionally, the sleep-related factors gamma-aminobutyric acid (GABA), glutamate (GA), 5-hydroxytryptamine (5-HT), and interleukin-6 (IL-6) were measured using enzyme linked immunosorbent assay. Finally, we screened potential sleep-improving receptors of DOE using polymerase chain reaction (PCR) array and validated the results with quantitative PCR and immunohistochemistry. RESULTS: DOE significantly improved rats' sleep and mood, increased the sodium pentobarbital-induced sleep time and sucrose preference index, and reduced autonomic activity times (P<0.05 or P<0.01). DOE also had a good effect on metabolic abnormalities, significantly reducing triglyceride, blood glucose, blood pressure, and blood viscosity indicators (P<0.05 or P<0.01). DOE significantly increased the GABA content in hippocampus and reduced the GA/GABA ratio and IL-6 level (P<0.05 or P<0.01). In addition, DOE improved the pathological changes such as the disorder of cell arrangement in the hippocampus and the decrease of Nissel bodies. Seven differential genes were screened by PCR array, and the GABA_A receptors (Gabra5, Gabra6, Gabrq) were selected for verification. The results showed that DOE could up-regulate their expressions (P<0.05 or P<0.01). CONCLUSION DOE demonstrated remarkable potential for improving insomnia, which may be through regulating GABA_A receptors expressions and GA/GABA ratio.
Animals ; Dendrobium/chemistry* ; Rats, Sprague-Dawley ; Male ; Sleep Initiation and Maintenance Disorders/blood* ; Plant Extracts/therapeutic use* ; Receptors, GABA-A/metabolism* ; Noise/adverse effects* ; Light/adverse effects* ; gamma-Aminobutyric Acid/metabolism* ; Sleep/drug effects* ; Rats ; Receptors, GABA/metabolism*

OBJECTIVE: To observe the clinical effect and safety of Lu'e Biyan Formula (LBF) combined with loratadine in the treatment of moderate to severe allergic rhinitis (AR) patients with Fei (Lung)-qi deficiency-coldness (FQDC) syndrome. METHODS: From September 2023 to December 2024, moderate to severe AR patients with FQDC syndrome were recruited from the Outpatient Department of Integrated Traditional Chinese and Western Medicine for Pulmonary Diseases Part 1, China-Japan Friendship Hospital. Participants were randomly assigned to a test group and a control group by using a random number table at a ratio of 1:1. Both groups received oral loratadine tablets (10 mg, once daily) for 2 weeks. In addition, the test group received oral LBF (30 mL, twice daily), and the control group received a placebo of LBF. Changes in the Total Nasal Symptom Score (TNSS), Total Non-nasal Symptom Score (TNNSS), Visual Analog Scale (VAS), Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ), and Chinese medicine (CM) syndrome scores before and after treatment were compared between groups. Moreover, the total effective rates and disease recurrence rates were compared. Adverse events (AEs) during the study period were also recorded. RESULTS: Totally 109 participants were recruited, and the full analysis set included 105 cases, 54 in the test group and 51 in the control group. Compared with the pre-treatment values, the scores of sneezing, runny nose, nasal obstruction, nasal itching, TNSS, TNNSS, VAS, RQLQ, and CM syndrome were significantly reduced in both groups at 1 and 2 weeks post-treatment and 12 weeks post-drug withdrawal (P<0.01). After treatment, the aforementioned scores in the test group were all markedly lower than those in the control group (P<0.01). Moreover, the total effective rate in the test group was higher than that in the control group (98.15% vs. 70.59%, P<0.01). After 12 weeks of drug withdrawal, there was no significant difference in the recurrence rate between groups (13.21% vs. 22.22%, P>0.05). No obvious AEs were observed in either group following treatment. CONCLUSIONS The combination of LBF with loratadine can effectively alleviate the symptoms of moderate to severe AR patients with FQDC syndrome, thereby improving their quality of life. This therapy demonstrated both precise effect and high safety. (Trial registration No. ITMCTR2025000589).
Humans ; Drugs, Chinese Herbal/therapeutic use* ; Male ; Rhinitis, Allergic/drug therapy* ; Female ; Adult ; Double-Blind Method ; Quality of Life ; Qi ; Middle Aged ; Loratadine/therapeutic use* ; Medicine, Chinese Traditional ; Syndrome ; Lung/drug effects* ; Young Adult ; Treatment Outcome

OBJECTIVE: To elucidate the specific mechanisms by which electroacupuncture (EA) alleviates anxiety and fear behaviors associated with posttraumatic stress disorder (PTSD), focusing on the role of lipocalin-2 (Lcn2). METHODS: The PTSD mouse model was subjected to single prolonged stress and shock (SPS&S), and the animals received 15 min sessions of EA at Shenmen acupoint (HT7). Behavioral tests were used to investigate the effects of EA at HT7 on anxiety and fear. Western blotting and enzyme-linked immunosorbent assay were used to quantify Lcn2 and inflammatory cytokine levels in the prefrontal cortex (PFC). Additionally, the activity of PFC neurons was evaluated by immunofluorescence and in vivo electrophysiology. RESULTS: Mice subjected to SPS&S presented increased anxiety- and fear-like behaviors. Lcn2 expression in the PFC was significantly upregulated following SPS&S, leading to increased expression of the proinflammatory cytokines tumor necrosis factor-α and interleukin-6 and suppression of PFC neuronal activity. However, EA at HT7 inhibited Lcn2 release, reducing neuroinflammation and hypoexcitability in the PFC. Lcn2 overexpression mitigated the effects of EA at HT7, resulting in anxiety- and fear-like behaviors. CONCLUSION EA at HT7 can ameliorate PTSD-associated anxiety and fear, and its mechanism of action appears to involve the inhibition of Lcn2-mediated neural activity and inflammation in the PFC. Please cite this article as: Yang YD, Zhong W, Chen M, Tang QC, Li Y, Yao LL, et al. Electroacupuncture alleviates behaviors associated with posttraumatic stress disorder by modulating lipocalin-2-mediated neuroinflammation and neuronal activity in the prefrontal cortex. J Integr Med. 2025; 23(5):537-547.
Electroacupuncture ; Stress Disorders, Post-Traumatic/metabolism* ; Animals ; Lipocalin-2/metabolism* ; Prefrontal Cortex/physiopathology* ; Male ; Mice ; Neurons/physiology* ; Disease Models, Animal ; Fear ; Behavior, Animal ; Mice, Inbred C57BL ; Neuroinflammatory Diseases/metabolism* ; Anxiety/therapy* ; Acupuncture Points

Objective To investigate the risk factors for bronchopulmonary dysplasia(BPD)in twin preterm infants with a gestational age of<34 weeks,and to provide a basis for early identification of BPD in twin preterm infants in clinical practice.Methods A retrospective analysis was performed for the twin preterm infants with a gestational age of<34 weeks who were admitted to 22 hospitals nationwide from January 2018 to December 2020.According to their conditions,they were divided into group A(both twins had BPD),group B(only one twin had BPD),and group C(neither twin had BPD).The risk factors for BPD in twin preterm infants were analyzed.Further analysis was conducted on group B to investigate the postnatal risk factors for BPD within twins.Results A total of 904 pairs of twins with a gestational age of<34 weeks were included in this study.The multivariate logistic regression analysis showed that compared with group C,birth weight discordance of>25%between the twins was an independent risk factor for BPD in one of the twins(OR=3.370,95%CI:1.500-7.568,P<0.05),and high gestational age at birth was a protective factor against BPD(P<0.05).The conditional logistic regression analysis of group B showed that small-for-gestational-age(SGA)birth was an independent risk factor for BPD in individual twins(OR=5.017,95%CI:1.040-24.190,P<0.05).Conclusions The development of BPD in twin preterm infants is associated with gestational age,birth weight discordance between the twins,and SGA birth.

Aim To investigate the synergistic sensiti-zation effect of saikosaponin D(SSD)combined with temozolomide(TMZ)on glioblastoma cells(GBM)and its molecular mechanism.Methods The sensitiv-ity of RG-2,U251 and LN-428 GBM cell lines to SSD and TMZ was analyzed by CCK-8 method combined with HE staining,and the optimal compatible concen-tration was screened.The effect of HE staining com-bined with Hoechst fluorescence staining on the prolif-eration of GBM cell line was detected by clonal forma-tion experiment.The autophagosome formation of GBM cells was observed by monodansylcadaverine(MDC)staining.The expression and distribution of endoplas-mic reticulum stress-related factors and apoptosis and autophagy proteins were detected by Western blot and ICC.Results The sensitivity order of GBM cells to TMZ was RG-2＞U251＞LN-428.The results of com-bined administration showed the synergistic inhibitory effect of SSD combined with TMZ on proliferation of GBM cell lines,which was confirmed by cell cloning formation experiment.Compared with the TMZ group,Hoechst fluorescence staining showed a significant in-crease in the number of nuclear bright staining in the combined administration group.MDC fluorescence staining showed that there were more dense green parti-cles in the cytoplasm of SSD/TMZ plus group than that of TMZ group.Western blot results showed that com-pared with TMZ group,the expression of ER stress markers GRP78,CHOP,p-PERK and ATF6 signifi-cantly increased in SSD/TMZ group(P＜0.05).The expressions of apoptosis proteins caspase-12,caspase-9,caspase-3,cleaved caspase-3,Bax and autophagy proteins LC3 and Beclin-1 significantly increased(P＜0.05),which were verified by ICC test.Conclusions SSD can cooperate with TMZ to inhibit the prolifera-tion of GBM cells and induce apoptosis and autophagy,and enhance the sensitivity of GBM cells to TMZ by ac-tivating endoplasmic reticulum stress pathway.

Objective: To investigate the epidemiological characteristics of human adenovirus (HADV) 2, 3 and 7 in hospitalized children with respiratory infection. Methods: A total of 25 686 children with respiratory infection hospitalized at Children's Hospital of Hebei Province from January 2018 to December 2020 were retrospectively included.Deep sputum or nasopharyngeal aspirates of those children were collected. Then thirteen common respiratory pathogens were detected by multiplex PCR. 510 HADV positive specimens were randomly selected via random number and classified for type 2, 3 and 7 using a multiplex real-time quantitative PCR. SPSS 21.0 software was used to perform all of the statistical analyses. Enumeration data were expressed by frequency and percentage. χ² test was used for comparison between groups. Results: The HADV-positive rate was 7.99% (2 052/25 686). Children at age 3-<6 years had the highest HADV-positive rate (11.44%). The HADV-positive rate in 2019 was highest (10.64%). Among the 510 HADV-positive specimens, the proportion of type 3 was the highest (31.16%), followed by type 7 (21.37%) and type 2 (11.18%). The rate of type 2 in 2019 was significantly lower than that in 2018 and 2020 (χ²=8.954 and 16.354; P=0.003 and <0.01), while the rate of type 3 was significantly higher than that in 2018 and 2020 (χ²=5.248 and 4.811; P=0.022 and 0.028). The rate of type 2, type 3 and type 7 were lowest in winter, spring and autumn, respectively. The rate of type 2 increased significantly in autumn and the rate of type 3 and type 7 increased significantly in winter.The co-detection rate of HADV with other respiratory pathogens was 43.33%(221/510). Among, the co-detection rate of type 3 was highest (47.32%), and the co-detection rate of type 2, 3 and 7 was significantly higher than the alone detection rate (χ²=20.438, P<0.01; χ²=42.105, P<0.01; χ²=27.573, P<0.01).The proportion of severe pneumonia in children with type 7 positive (15.89%) was higher than that in children with non-type 7 positive (8.23%) (χ²=5.260, P=0.022). Conclusion: HADV is one of the important pathogens of children with respiratory infection in Children's Hospital of Hebei Province. The susceptible population of HADV is preschool children aged 3 to 6 years. HADV often co-detects with other respiratory pathogens. Type 3 and 7 is likely to be the dominant genotypes in this region, and type 7 may be one of the risk factors of severe pneumonia in children.
Child, Preschool ; Child ; Humans ; Infant ; Adenoviruses, Human/genetics* ; Child, Hospitalized ; Retrospective Studies ; Adenovirus Infections, Human/epidemiology* ; Respiratory Tract Infections/epidemiology* ; Pneumonia ; Hospitals

This study aims to examine the effect of superfine powder and aqueous extract of Polygonati Rhizomaon on natural perimenopausal syndrome in rats and explore the underlying mechanism. To be specific, a total of 60 female SD rats(14-15 months old) with estrous cycle disorder were screened by the vaginal smear and randomized into model control group, β-estradiol 3-benzoate group(0.1 mg·kg~(-1)), superfine powder of Polygonati Rhizoma group(0.25, 0.5 g·kg~(-1)) and aqueous extract of Polygonati Rhizoma group(0.25, 0.5 g·kg~(-1)), and another 10 female SD rats(14-15 months old) were selected as the youth control group. The administration lasted 6 weeks. Then the perimenopausal syndrome-related indexes such as body temperature, microcirculatory blood flow of face and ear, vertigo period, salivary secretion, grip force, and bone strength were determined and open field test was conducted. The immune system-related indexes such as the wet weight and index of thymus and spleen, percentage of T lymphocytes and subgroups in peripheral blood, and hematological indexes were measured. In addition, the ovary-related indexes such as estrous cycle, the wet weight and index of uterus and ovary, ovarian tissue morphology, and cell apoptosis were determined. Moreover, hypothalamus-pituitary-ovary axis(HPO)-related indexes such as serum sex hormone levels, cytochrome P450 family 11 subfamily A member 1(CYP11A1), cytochrome P450 family 19 subfamily A member 1(CYP19A1), and cytochrome P450 family 17 subfamily A member 1(P450 17A1) in ovarian tissue were measured. The results showed that the superfine powder and aqueous extract of Polygonati Rhizoma significantly decreased body temperature(anal, facial and dorsal temperature), microcirculatory blood flow in the ear, and vertigo period, increased salivary secretion, grip force, bone strength, total distance and total speed in the open field test, wet weight and index of thymus and spleen, lymphocyte ratio, CD3~+ level, and CD4~+/CD8~+ ratio, reduced neutrophil number and ratio, estrous cycle disorder ratio, and number of ovarian apoptotic cells, raised wet weight and index of uterus, wet weight of ovary, levels of inhibin B(INHB), estradiol(E_2), anti-müllerian hormone(AMH), and ovarian CYP11A1 and CYP19A1, decreased follicle-stimulating hormone(FSH) and luteinizing hormone(LH) content, and improved ovarian tissue morphology. It is suggested that the superfine powder and aqueous extract of Polygonati Rhizoma can improve the symptoms associated with natural perimenopausal syndrome in rats and enhance ovarian function and immune function. The mechanism is that they regulate HPO axis function by increasing estrogen synthesis.
Female ; Animals ; Rats ; Rats, Sprague-Dawley ; Microcirculation ; Cholesterol Side-Chain Cleavage Enzyme ; Perimenopause ; Powders ; Cytochrome P-450 CYP1A1

Objective:To analyze influencing factors of coronary heart disease(CHD)in advanced aged population and the therapeutic effect of percutaneous coronary intervention(PCI).Methods:According to diagnosed as CHD or not,a total of 209 aged patients underwent cardio-and cerebrovascular examination in our hospital were divided into CHD group(n=104)and no CHD group(n=105),and general clinical data were compared between two groups.According to treatment method,CHD group was divided into routine treatment group(received routine medication)and PCI group;and recovery time,hospital stay,incidence rate of adverse events during admission and prognosis within one-year follow-up were compared between two groups.Influencing factors of CHD in aged population was analyzed.Results:Compared with no CHD group,there were significant rise in percentages of age＞80 years,smoking,diabetes mellitus,hypertension,total cholesterol＞5.17mmol/L,triglyceride＞1.7mmol/L,high density lipoprotein cholesterol(HDL-C)＜0.96mmol/L,low density lipoprotein cholesterol＞3.37mmol/L,uric acid＞420μmol/L and fibrinogen＞4 g/L in CHD group(P＜0.05 or＜0.01).Compared with routine treat-ment group,there were significant reductions in recovery time,hospital stay,incidence rates of adverse events,lu-men loss/restenosis,primary and secondary endpoint events within one-year follow-up in PCI group(P＜0.05 or＜0.01).Binary Logistic regression analysis indicated that age＞80 years,uric acid＞420μmol/L and HDL-C＜0.96mmol/L were independent risk factors for CHD in advanced aged population(OR=1.755～6.103,P＜0.05 or＜0.01).Conclusion:Age＞80 years,uric acid＞420μmol/L and HDL-C＜0.96 mmol/L are independent risk fac-tors for coronary heart disease in advanced aged population.PCI can significantly shorten recovery time and treat-ment time in advanced aged patients with coronary heart disease with good safety.