To summarize the clinical experience of treating idiopathic olfactory disorder from the perspective of heart and lungs. It is believed that the sense of olfaction is based on the nose， rooted in the heart， functioning through the lungs， and conveyed by pectoral qi. The key pathogenesis of idiopathic olfactory disorder lies in the accumulation of pathogenic factors in the heart and lungs， blood vessel obstruction， the failure of the lungs to disperse and descend， and the loss of control of pectoral qi. In treatment， internal and external therapies could be combined. The internal therapy can correct the imbalance of the zang-fu organs， using the self-prescribed Bilong Formula （鼻聋方） to dispel wind and diffuse the lung， invigorate blood and relieving stuffy orifices； the external therapy can clear nasal obstruction， supplemented by intradermal needle embedding at three acupoints， bilateral Yingxiang （LI 20）， bilateral Shangyingxiang （EX-HN 8） and Yintang （GV 29）， and integrated olfactory training for comprehensive treatment.

BACKGROUND:Psoralen has a strong anti-osteoporotic activity and may have a restorative effect on chemotherapy-induced osteoporosis. OBJECTIVE:To explore the restorative effect of psoralen on the osteogenic differentiation of bone marrow mesenchymal stem cells in mice inhibited by cyclophosphamide and its mechanism. METHODS:C57BL/6 mouse bone marrow mesenchymal stem cells were isolated and cultured.Effect of psoralen on viability of bone marrow mesenchymal stem cells was detected by MTT assay.Osteogenic induction combined with alkaline phosphatase staining was used to determine the optimal dose of psoralen to restore the osteogenic differentiation of bone marrow mesenchymal stem cells inhibited by cyclophosphamide.The mRNA expression levels of Runx2,alkaline phosphatase,Osteocalcin,osteoprotegerin,and Wnt/β-catenin signaling pathway-related genes Wnt1,Wnt4,Wnt10b,β-catenin,and c-MYC were measured by RT-qPCR at different time points under the intervention with psoralen.The protein expression of osteogenic specific transcription factor Runx2 and Wnt/β-catenin signaling pathway related genes Active β-catenin,DKK1,c-MYC,and Cyclin D1 was determined by western blot assay at different time points under the intervention with psoralen. RESULTS AND CONCLUSION:(1)There was no significant effect of different concentrations of psoralen on the viability of bone marrow mesenchymal stem cells.The best recovery of the inhibition of osteogenic differentiation of bone marrow mesenchymal stem cells caused by cyclophosphamide was under the intervention of psoralen at a concentration of 200 μmol/L.(2)Psoralen reversed the reduction in osteogenic differentiation marker genes Runx2,alkaline phosphatase,Osteocalcin and osteoprotegerin mRNA expression and Runx2 protein expression in bone marrow mesenchymal stem cells caused by cyclophosphamide conditioned medium.(3)Psoralen reversed the decrease in Wnt/β-catenin pathway-related genes Wnt4,β-catenin,c-MYC mRNA and Active β-catenin,c-MYC,and Cyclin D1 protein expression and the increase in DKK1 protein expression in bone marrow mesenchymal stem cells caused by cyclophosphamide conditioned medium.(4)The results showed that cyclophosphamide inhibited osteogenic differentiation of bone marrow mesenchymal stem cells in mice,and psoralen had a restorative effect on it.The best intervention effect was achieved at a concentration of 200 μmol/L psoralen,and this protective effect might be related to the activation of Wnt4/β-catenin signaling pathway by psoralen.

OBJECTIVE: To compare the protective effects of electroacupuncture (EA) and transcutaneous electrical acupoint stimulation (TEAS) during pregnancy on maternal immune activation (MIA)-induced adverse pregnancy outcomes, fetal developmental defects, and neuropsychological behavior abnormalities in offspring mice. METHODS: Eighty pregnant C57BL/6 mice were randomly divided into 5 groups: control, model, EA, TEAS, and sham-stimulation groups, 16 mice in each group. MIA models were replicated on the day 12.5 of pregnancy via tail intravenous injection with polyinosinic-polycytidylic acid. On the second day of modeling success, in the EA and TEAS groups, the interventions were delivered at bilateral "Zusanli" (ST36), with a frequency of 2 Hz, a current of 0.5 mA, and for 20 min each day in the pregnant mice; and the interventions lasted 6 days. Body mass and fertility indexes of pregnant mice, and the development indexes of offspring mice were recorded. Liquid phase suspension chip technology was used to detect the levels of cytokines and chemotactic factors in the serum of pregnant mice and and fetal brain of offspring mice. Flow cytometry was adopted to detect the proportion of the subgroups and subtypes of spleen T lymphocytes and macrophages in pregnant mice. Using the open field test, prepulse inhibition (PPI) test and Morris water maze, the spatial learning and memory were assessed in offspring mice. Immunofluorescence staining was used to detect microglial count in the medial prefrontal cortex (mPFC) in offspring mice. RESULTS: Compared with the control group, the model group showed a reduced body mass of pregnancy mice (P<0.01), smaller litter size and fewer live births (P<0.01, P<0.05), the increase in dead birth and the decrease in offspring survival rate (P<0.05, P<0.01). When compared with model group, in the EA group and the TEAS group, the body mass of pregnancy mice rose (P<0.05), litter size and live births increased (P<0.05, P<0.01), the dead birth was reduced and the offspring survival rate higher (P<0.05). In comparison with the control group, the model group showed the increase in the levels of monocyte chemotactic protein-1 (MCP-1), interleukin-6 (IL-6), γ-interferon (IFN-γ) in the serum of pregnant mice, and spleen M1 macrophage proportion (P<0.01, P<0.05), and the decrease in spleen M2 macrophages of pregnant mice (P<0.01); and the increase in MCP-1 and IL-6 in fetal brain of offspring mice (P<0.05). Compared with the model group, the EA group and the TEAS group showed the decrease in MCP-1, IL-6 and IFN-γ, and spleen M1 macrophage proportion (P<0.01, P<0.05), and the increase in spleen M2 macrophages of pregnant mice (P<0.01, P<0.05) ; and the decrease in MCP-1 and IL-6 in fetal brain of offspring mice (P<0.05). Compared with the control group, in the model group, the total movement distance, escape incubation were extended (P<0.05, P<0.01), the frequency of entering the central area and crossing the platform decreased, and the activity duration in central area was shortened (P<0.05, P<0.01), the average speed rose (P<0.05), PPI%, the percentage of target quadrant swimming time in the total time and that of target quadrant swimming distance in the total distance were reduced (P<0.05, P<0.01) in offspring mice. When compared with the model group, in the EA group and TEAS group, the total movement distance and escape incubation were shortened, the average speed was reduced (P<0.05), PPI% and the frequency of crossing the platform increased (P<0.05, P<0.01); the percentage of target quadrant swimming time in the total time and that of target quadrant swimming distance in the total distance rose (P<0.05, P<0.01) in the offspring mice. In the EA group, the frequency of entering the central area and the activity duration in central area were higher (P<0.05, P<0.01); and in the the TEAS group, the activity duration in central area were longer (P<0.05). When compared with the control group, in the model group, microglial count in mPFC was elevated in offspring mice (P<0.05). In comparison with the model group, the EA group and the TEAS group showed the decrease of microglial count in mPFC (P<0.05). CONCLUSION EA and TEAS at "Zusanli" (ST36) during pregnancy effectively improve in the pregnancy outcomes and fetal brain developmental abnormalities induced by infection, and attenuate neurodevelopmental defects and mental disorders of offspring mice through inhibiting inflammatory activation of microglia in mPFC.
Animals ; Female ; Pregnancy ; Electroacupuncture ; Acupuncture Points ; Mice ; Mice, Inbred C57BL ; Humans ; Male

Very early onset inflammatory bowel disease (VEO-IBD) in children refers to an IBD with the onset age of less than 6 years old, clinically characterized by recurrent colitis, perianal lesions, and nutrient absorption disorders.Different from adults, single gene mutation plays an important role in the pathogenesis of VEO-IBD.To date, about 70 single gene defects have been identified involving the pathogenesis of VEO-IBD, including epithelial barrier, neutrophil and phagocyte function, immune cell selection and activation, immunosuppressive mechanism, or apoptosis.Interleukin-10 (IL-10) is an anti-inflammatory cytokine that regulates innate and adaptive immunity, influences the expression of pro-inflammatory molecules and the function of multiple immune cells, and plays a vital role in the development and progression of IBD.Patients with defects in the IL-10 signaling pathway (IL-10 or IL-10 receptor deficiency) may develop life-threatening colitis as early as childhood.This article reviews the progress in the pathogenesis and treatment of VEO-IBD caused by IL-10 signaling pathway defects.

ObjectiveTo study the mechanism of astragaloside Ⅳ （AS Ⅳ） on db/db mice with type 2 diabetes mellitus （T2DM） and non-alcoholic fatty liver disease （NAFLD） based on network pharmacology and experimental validation. MethodA total of 24 db/db mice were randomly divided into four groups： model group， metformin group， and low-dose and high-dose AS Ⅳ groups. Six C57 mice were used as the blank group. The low-dose and high-dose AS Ⅳ groups were given AS Ⅳ of 0.015 and 0.030 g·kg^-1 by gavage， and the metformin group was given 0.067 g·kg^-1 by gavage. The blank and model groups were given equal volumes of distilled water by gavage. After intragastric administration， fasting blood glucose （FBG） was detected， and an oral glucose tolerance test was performed. Serum lipid level and liver histopathology were detected. The target and enrichment pathway of AS Ⅳ for treating T2DM and NAFLD were predicted by network pharmacology， and the main enrichment pathway was verified by molecular biology techniques. The protein expressions of AMPK， p-AMPK， sterol regulatory element-binding protein-1 （SREBP-1）， and fatty acid synthetase （FAS） in liver tissue were detected by Western blot. ResultCompared with the blank group， the levels of body mass， liver weight coefficient， fasting blood glucose， serum total cholesterol， triglyceride， and low-density lipoprotein cholesterol in mice treated with AS Ⅳ were decreased （P<0.05， P<0.01）. The pathology of liver tissue showed significant improvement in lipid accumulation， and imaging results showed that the degree of fatty liver was reduced after AS Ⅳ therapy. Network pharmacological prediction results showed that vascular endothelial growth factor α （VEGFA）， galactoagglutinin 3 （LGALS3）， serine/threonine kinase B2 （Akt2）， RHO-associated coiled-coil protein kinase 1 （ROCK1）， serine/threonine kinase B1 （Akt1）， signaling and transcriptional activator protein （STAT3）， and messtimal epidermal transformation factor （MET） were key targets in "drug-disease" network. The results from the Kyoto encyclopedia of genes and genomes （KEGG） enrichment showed that the AMP-dependent protein kinase （AMPK） signaling pathway was strongly associated with T2DM and NAFLD. Western blot results showed that compared with the blank group， the expression levels of p-AMPK/AMPK in the model group were significantly down-regulated， while those of SREBP-1 and FAS proteins were significantly up-regulated （P<0.01）. Compared with the model group， the expression levels of p-AMPK/AMPK in the metformin group and high-dose AS Ⅳ group were significantly up-regulated， while those of SREBP-1 and FAS proteins were significantly down-regulated （P<0.05， P<0.01）. ConclusionAS Ⅳ regulates the expression of lipid proteins by activating the AMPK signaling pathway， thereby improving lipid metabolism.

OBJECTIVE To analyze the influential factors on trough concentration （cmin） and area under the drug concentration time curve （AUC） of voriconazole （VRZ） in pediatric patients with thalassemia undergoing hematopoietic stem cell transplantation （HSCT）. METHODS A total of 60 pediatric patients with thalassemia undergoing HSCT who used VRZ for prevention or treatment of invasive fungal infection were collected in our hospital from January 2021 to January 2024. The plasma concentration of VRZ was measured by high-performance liquid chromatography and the AUC was calculated. The factors affecting cmin and AUC of VRZ were analyzed using multiple linear regression. RESULTS A total of 120 cases of VRZ cmin in 60 pediatric patients was obtained and 27 cases of VRZ AUC in 26 pediatric patients were obtained. The median concentration of VRZ cmin was 0.31 mg/L； 46 cases had a cmin in 0.5-5 mg/L（ 38.33%）， 2 cases had a cmin＞5 mg/L（ 1.67%）， and 72 cases had a cmin＜0.5 mg/L. The median AUC of VRZ was 11.68 mg·h/L. The patient’s body weight， HSCT postoperative days， lymphocyte count， and combined use of phenytoin sodium， tacrolimus or cyclosporine had significant effects on VRZ cmin （P＜0.05）. Lymphocyte count and combined use of phenytoin sodium had significant effects on VRZ AUC （P＜0.05）. CONCLUSIONS The body weight， HSCT postoperative days， lymphocyte count， and combined use of phenytoin sodium， tacrolimus or cyclosporine are independent factors affecting VRZ cmin. Lymphocyte count and combined use of phenytoin sodium are independent factors affecting VRZ AUC.

Objective To explore the feasibility and accuracy of neutrophil-to-lymphocyte ratio(NLR)in the prediction of testicular torsion(TT)in children with acute scrotal pain.Methods A retrospective case-control study was performed on 158 pediatric patients with ultrasound suspicion of TT who underwent surgical testicular examination during Jan.2017 and Jan.2024.The patients were divided into TT group and non-TT group.Clinical data and laboratory data at admission were analyzed.Sensitivity and specificity of NLR to TT were determined with the area under the curve(AUC)represented on the receiver operating characteristic(ROC)curves.Results There were with no statistically significant differences in clinical data between the two groups(P＞0.05).The NLR was significantly higher in the TT group than in the non-TT group[(4.82±2.37)vs.(2.85±0.75),P＜0.05].The optimal cut-off value of TT predicted by NLR was 2.07,the AUC was 0.809(95％CI:0.709-0.909),and the sensitivity and specificity were 97.9％and 93.3％,respectively,which were significantly higher than other factors.Conclusion For suspicious ultrasound diagnosis of pediatric acute scrotal pain cases,NLR can be used to predict the possibility of TT and may help to evaluate the urgent surgical treatment in these patients.

Lung cancer is the leading type of cancer death, and most patients with lung cancer are diagnosed at an advanced stage and have a very poor prognosis. Although low-dose computed tomography (LDCT) has entered the clinic as a screening tool for lung cancer, its false-positive rate is more than 90%. As one of the epigenetic modifications of research hotspots, DNA methylation plays a key role in a variety of diseases, including cancer.Hypermethylation of tumor suppressor genes and hypomethylation of proto-oncogenes are important events in tumorigenesis and development. Therefore, DNA methylation analysis can provide some useful information for the early screening, diagnosis, treatment and prognosis of lung cancer. Although invasive methods such as tissue biopsy remain the gold standard for tumor diagnosis and monitoring, they also have limitations such as inconvenience in sampling. In recent years, there has been a rapid development of liquid biopsy, which can detect primary or metastatic malignancies and reflect the heterogeneity of tumors. In addition, the blood sample can be collected in a minimally invasive or non-invasive format and is well tolerated in older and frail patients. This article explores some of the emerging technologies for DNA methylation analysis and provides an overview of the application of DNA methylation in the diagnosis and treatment of lung cancer.

Replantation of traumatic amputation in children has its own characteristics. This consensus primarily focuses on the issues related to the treatment of traumatically amputated limb injuries in children. Organised along a timeline, the consensus summarises domestic and international clinical experiences in emergency care and injury assessment of traumatic limb amputation limbs, indications and contraindications for replantation surgery, principles and procedures of replantation surgery, postoperative medication and management, as well as rehabilitation in children. The aim of this consensus is to propose standardise the treatment protocols for limb replantation for children therefore to serve as a reference for clinical practitioners in medical practices, and further improve the treatment and care for the traumatic limb amputations in children.

Objective:To investigate the predictive value of left ventricular global longitudinal peak strain (GLPS) for the prognosis of septic patients.Methods:A prospective cohort study was conducted. Patients diagnosed with sepsis and admitted to the intensive care unit (ICU) of the First Affiliated Hospital, Sun Yat-sen University from December 2018 to November 2019 were enrolled. The patient characteristics, cardiac ultrasound parameters [left ventricular ejection fraction (LVEF), right ventricular ejection fraction (RVEF), four-dimensional ejection fraction (4DEF), GLPS] and cardiac biomarkers [N-terminal pro-brain natriuretic peptide (NT-proBNP), cardiac troponin T (cTnT)] within 24 hours of ICU admission, organ support therapies, severity of illness, and prognostic indicators were documented. The differences in clinical parameters between patients with varying outcomes during ICU hospitalization were assessed. Pearson correlation analysis was employed to explore the correlation between GLPS and other cardiac systolic parameters, as well as the associations between various cardiac systolic parameters and sequential organ failure assessment (SOFA) score. Receiver operator characteristic curve (ROC curve) was drawn to analyze the predictive capacity of cardiac ultrasound parameters and cardiac biomarkers for death during ICU hospitalization in septic patients.Results:A total of 50 septic patients were enrolled, with 40 surviving and 10 dying during ICU hospitalization, resulting in a mortality of 20.0%. All patients in the death group were male. Compared with the survival group, the patients in the death group were older, had a higher prevalence of diabetes mellitus, and received continuous renal replacement therapy (CRRT) more frequently, additionally, they exhibited more severe illness and had longer length of ICU stay. The levels of GLPS and cTnT in the death group were significantly elevated as compared with the survival group [GLPS: -7.1% (-8.5%, -7.0%) vs. -12.1% (-15.5%, -10.4%), cTnT (μg/L): 0.07 (0.05, 0.08) vs. 0.03 (0.02, 0.13), both P < 0.05]. However, no statistically significant difference was found in other cardiac ultrasound parameters or cardiac biomarkers between the two groups. Pearson correlation analysis revealed a negative correlation between GLPS and LVEF ( r = -0.377, P = 0.014) and 4DEF ( r = -0.697, P = 0.000), while no correlation was found with RVEF ( r = -0.451, P = 0.069). GLPS demonstrated a positive correlation with SOFA score ( r = 0.306, P = 0.033), while LVEF ( r = 0.112, P = 0.481), RVEF ( r = -0.134, P = 0.595), and 4DEF ( r = -0.251, P = 0.259) showed no significant correlation with SOFA score. ROC curve analysis indicated that the area under the ROC curve (AUC) of GLPS for predicting death during ICU hospitalization in septic patients was higher than other cardiac systolic parameters, including LVEF, RVEF, and 4DEF, as well as cardiac biomarkers NT-proBNP and cTnT (0.737 vs. 0.628, 0.556, 0.659, 0.580 and 0.724). With an optimal cut-off value of -14.9% for GLPS, the sensitivity and negative predictive value reached to 100%. Conclusion:GLPS < -14.9% within 24 hours of ICU admission in septic patients indicated a reduced risk of death risk during ICU hospitalization, while also correlating with the severity of organ dysfunction in this patient population.