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 explore the changes in serum energy metabolites in patients with peripheral T-cell lymphoma,and investigate serum biomarkers for monitoring peripheral T-cell lymphoma from the perspective of energy metabolism.Methods Multiple/selected reaction monitoring(MRM/SRM)was used to detect the energy-related metabolites in the sera of 16 patients with newly diagnosed peripheral T-cell lymphoma admitted in the Hematology Medical Center of the Second Affiliated Hospital of Army Medical University from November 2020 to December 2021,as well as 10 recruited healthy volunteers.The corresponding clinical data including medical history,laboratory results and image data were collected and retrospectively analyzed.Results Significant differences were seen in the contents and expression profiles of serum energy metabolism-related products between the patients and the healthy volunteers.The patients had significantly reduced serum contents of cyclic AMP,succinate,citrate and cis-aconitate(P＜0.05),and elevated D-glucose 6-phosphate content(P＜0.05).The serum contents of citrate and succinate were negatively correlated with the risk stratification(low-,moderate-and high-risk)and clinical stage of the disease(P＜0.05).Meanwhile,there was a negative correlation between the contents of L-malic acid and citrate and the mid-term efficacy evaluation results,such as complete/partial response(CR/PR)or stable disease(SD)(P＜0.05).For patients with extranodal NK/T cell lymphoma(n=10),there were also significant reductions in the contents of cyclic AMP,succinate,citrate,isocitrate and cis-aconitate in the sera of patients compared with healthy volunteers(P＜0.05),and the contents of citrate and succinate were negatively correlated with the clinical stage(P＜0.05)and were rather correlated with mid-term efficacy evaluation results(CR/PR or SD)(P＜0.05).For patients with angioimmunoblastic T-cell lymphoma(n=6),the serum contents of cyclic AMP,citrate and succinate were significantly lower,while the content of D-glucose 6-phosphate was higher when compared with the healthy volunteers(P＜0.05),and the content of succinate was negatively correlated with both clinical stage and risk grade of the patients(P＜0.05).Conclusion There are 5 serum differential metabolites identified between patients with peripheral T-cell lymphoma and healthy controls,and succinate and citrate are expected to be serum biomarkers of peripheral T-cell lymphoma.

Objective:To explore the efficacy and safety of immunoneoadjuvant therapy with pembrolizumab combined with chemotherapy in locally advanced resectable hypopharyngeal squamous cell carcinoma patients.Methods:This study was a prospective, single arm, single center clinical study that was opened for enrollment in April 2021. Patients who met the inclusion criteria at the Cancer Hospital of the Chinese Academy of Medical Sciences were treated with neoadjuvant therapy of pembrolizumab combined with cisplatin and paclitaxel, and after treatments, received surgery and postoperative adjuvant therapy. The main endpoint of this study was postoperative pathological complete response (pCR), and other observations included adverse reactions and long-term prognoses of patients after neoadjuvant therapy.Results:By September 2023, a total of 23 patients who underwent neoadjuvant therapy and surgery were enrolled in the study and all patients were males aged 49-74 years. All patients were locally advanced stage, including 3 patients in stage Ⅲ and 20 patients in stage Ⅳ. There were 12 cases of primary lesions with posterior ring involvement accompanied by fixation of one vocal cord and 20 cases of regional lymph node metastases classified as N2. Eighteen cases received a two cycle regimen and 5 cases received a three cycle regimen for neoadjuvant therapy. The postoperative pCR rate was 26.1% (6/23), with no surgical delay caused by adverse drug reactions. The laryngeal preservation rate was 87.0% (20/23). Pharyngeal fistula was the main surgical complication, with an incidence of 21.7% (5/23). The median follow-up time was 15 months, and 3 patients experienced local recurrence.Conclusions:The immunoneoadjuvant therapy of pembrolizumab combined with chemotherapy has a high pCR rate in locally advanced resectable hypopharyngeal squamous cell carcinoma, with increased laryngeal preservation rate and no significant impact on surgical safety.

Background::Very low birth weight (VLBW) infants are the key populations in neonatology, wherein morbidity and mortality remain major challenges. The study aimed to analyze the clinical characteristics of VLBW infants.Methods::A retrospective cohort study was conducted in West China Second Hospital between January 2016 and December 2021. Neonates with a birth weight of <1500 g were included. Mortality, care practices, and major morbidities were analyzed, and compared with those of previous 7 years (2009-2015).Results::Of the total 1750 VLBW, 1386 were infants born with birth weight between 1000-1499 g and 364 infants were born with weight below 1000 g; 42.9% (751/1750) required delivery room resuscitation; 53.9% (943/1750) received non-invasive ventilation only; 38.2% (669/1750) received invasive ventilation; 1517 VLBW infants received complete treatment. Among them, 60.1% (912/1517) of neonates had neonatal respiratory distress syndrome (NRDS), 28.7% (436/1517) had bronchopulmonary dysplasia (BPD), 22.0% (334/1517) had apnea, 11.1% (169/1517) had culture-confirmed sepsis, 8.4% (128/1517) had pulmonary hemorrhage, 7.6% (116/1517) had severe intraventricular hemorrhage (IVH)/periventricular leukomalacia (PVL), 5.7% (87/1517) had necrotizing enterocolitis (NEC), and 2.0% (31/1517) had severe retinopathy of prematurity. The total and in-hospital mortality rates were 9.7% (169/1750) and 3.0% (45/1517), respectively. The top three diagnoses of death among those who had received complete treatment were sepsis, NRDS, and NEC. In 2009-2015, 1146 VLBW were enrolled and 895 infants received complete treatment. The proportions of apnea, IVH, and IVH stage ≥3/PVL, were higher in 2009-2015 compared with those in 2016-2021, while the proportions of NRDS and BPD were characterized by significant increases in 2016-2021. The total and in-hospital mortality rates were 16.7% (191/1146) and 5.6% (50/895) respectively in 2009-2015.Conclusion::Among VLBW infants born in 2016-2021, the total and in-hospital mortality rates were lower than those of neonates born in 2009-2015. Incidences of NRDS and BPD increased in 2016-2021, which affected the survival rates and long-term prognosis of VLBW.

Objective:To analyze the clinical characteristics, treatment methods, and efficacy of hemorrhagic supratentorial deep brain arteriovenous malformation(BAVM) in children.Methods:Clinical data of 12 pediatric patients with hemorrhagic supratentorial deep BAVM diagnosed and treated in the Department of Neurosurgery, Children′s Hospital of Nanjing Medical University from May 2020 to January 2023 were retrospectively analyzed.Among them, there were 7 males and 5 females, aged range from 4.8 to 14.1(9.6±3.2) years old.On the day of onset, the children underwent lateral external ventricular drainage, combined surgery, evacuation of intracranial hematoma, or medication to reduce intracranial pressure, based on the location of intracranial hemorrhage, degree of neurological dysfunction, and angioarchitecture of BAVM.Afterwards, the patients were given embolization with stable physical signs.The data of 12 patients were analyzed retrospectively, including clinical manifestations, imaging features, and treatment outcomes.Results:All 12 children started with intracranial hemorrhage.Digital subtraction angiography confirmed the diagnosis of deep BAVM, with 6 cases having the niduses in the splenium of the corpus callosum, 3 cases in the body of the corpus callosum, 2 cases in the basal ganglia area, and 1 case in the thalamus.Ten children had an intracranial hemorrhage in the lateral ventricle.Among them, 6 children underwent lateral external ventricular drainage on the day of onset and then were given BAVM embolization 7-14 days after onset; 1 patient experienced intraoperative bleeding, but showed no neurological dysfunction after surgery; 1 patient experienced temporary facial numbness; 1 patient with massive hemorrhages in the occipital lobe and lateral ventricle underwent combined surgery to embolize the BAVM and remove intracranial hematoma on the first day of onset; 1 patient suffered from basal ganglia hemorrhage with lateral intraventricular hemorrhage, and evacuation of intracranial hematoma was performed on the day of onset, and BAVM embolization was performed 7 days after surgery.Three months after combined surgery and embolization and 3 years after gamma knife treatment, the digital subtraction angiography was re-performed, and results showed that 5 cases, including 1 child undergoing combined surgery, was cured through a single interventional embolization, and 1 case was cured by a single embolization combined with gamma knife treatment.Conclusions:Intracranial hemorrhage caused by deep BAVM in children is mainly located in the lateral ventricle.In the acute phase, the main focus is on treating intracranial hypertension caused by obstructive hydrocephalus and intracranial parenchymal hematoma.Interventional embolization is safe and effective in the treatment of deep BAVM in children.

Lymphomas are a highly heterogeneous group of tumors that are classified into several subtypes. The gold standard method for the molecular profiling of lymphoma is based on invasive lymph node or tissue biopsy. However, this method cannot accurately capture spatial tumor heterogeneity in each patient as well as systemic tumor invasion and tumor burden. Circulating tumor DNA (ctDNA) is an emerging and highly versatile biomarker that overcomes the basic limitations of imaging scanning and tissue biopsy; has the characteristics of being simple, rapid, and non-invasive; and has good specificity and high sensitivity. ctDNA testing has been applied to a variety of subtypes of lymphoma and has been used for somatic mutation genotyping, efficacy monitoring during treatment, detection of minimal residual disease, and the prediction of survival, which may help clinicians make better clinical decisions in the diagnosis and treatment of lymphoma patients. Furthermore, this study also aims to review the different methods of ctDNA analysis and describe the specific applications of ctDNA in different lymphoma subtypes.

Objective The purpose of this study was to examine effects of Isopsoralen on the osteoblast proliferation and differentiation and find its possible molecular mechanisms for anti-osteoporosis.Methods OCT-1 cells were cultured with common methods.While growing well,cells were cultured with 3 doses(10 μg·mL-1,30u μg·mL-1 and 60 μg·mL-1)of Isopsoralen for 48 h,or with purified bone morphogenetic protein 2(BMP2)protein(50 ng·mL-1).We first determined the effect of Isopsoralen on cell proliferation by MTT assay.The real time RT-PCR was also used to quantify changes in the mRNA levels of several genes,such as BMP2,Runt-related transcription factor 2(Runx2),and Osterix(Osx).We also used the Western blot analysis to evaluate the expression of Runx2 and Osx proteins.At last we used the BMP2loxp/loxp mice to isolate the primary calvaria osteoblasts,cultured with Isopsoralen of the best dose for 48 h after the in vitro conditional gene knockout technology,and tested the gene expressions of Runx2 and Osx.And the alkaline Phosphatase(ALP)staining was also performed.Result Isopsoralen(10 μg·mL-1)can promote osteoblast proliferation obviously.From the real time RT-PCR analysis,Isopsoralen can enhance the BMP2 mRNA levels,the effect of 10 μg·mL-1 was the best,and 30 μg·mL-1 followed.In addition,we found that Isopsoralen(10 μg·mL-1)can enhance the Runx2 mRNA levels significantly.We also found that lower doses of Isopsoralen can enhance the Osx mRNA levels,the effect of 30 μg·mL-1 was the best,and 10 μg·mL-1 followed.From the Western blot analysis,low doses of Isopsoralen(10 μg·mL-1 and 30 μg·mL-1)can stimulate the expression of Runx2 protein.Besides,three doses of Isopsoralen can stimulate the expression of Osx protein,and the effect of 10 μg·mL-1 and 30 μg·mL-1 are better.Finally,the results of in vitro conditional gene knockout experiment showed that the overexpression of Runx2 and Osx genes in osteoblasts,as well as ALP staining,induced by Isopsoralen are BMP2 dependent.Conclusions In this study,we firstly demonstrate that Isopsoralen can stimulate osteoblast proliferation and differentiation by mediating BMP2/Runx2/Osx signaling pathway.

Objective: To understand the influence of junior middle school students health literacy on knowledge, belief and behavior of COVID-19 in rural areas of Jiangxi Province, and to enhance junior middle school students ability to deal with public health emergencies. Methods: Stratified cluster random sampling was used to investigate the health literacy, knowledge level and behavior of COVID-19 protection of 4 311 grade 7 to grade 8 students in rural areas of Jiangxi Province; Chi square test and Logistic regression analysis were used to analyze the correlation between junior high school students health literacy and COVID-19 protection knowledge, belief and behavior. Results: The rate of health literacy of junior middle school students in rural areas was 18.21 %( n =785), the reported rate of intermediate level was high ( n =2 454, 56.92%), and the reported rate of junior high school students at a low level of health literacy was 24.87%( n =1 072). The rate of junior middle school students in rural areas with good COVID-19 protection knowledge was 63.49%, the rate of positive protection attitude was 74.25%, and the rate of good protection behavior was 85.36%; Rate of COVID-19 protection knowledge ( OR=4.85, 95%CI =3.80-6.18) and positive rate of protection attitude of high level health literacy ( OR=44.07, 95%CI =24.57-79.05), protective behavior possession rate ( OR=25.99, 95%CI = 19.67-34.35) were higher than those with low level of health literacy( P <0.01). Conclusion Health literacy is associated with COVID-19 protection knowledge, belief and behavior in rural junior high school students of Jiangxi Province, the findings provide direction for junior middle school students to improve their ability to deal with public health emergencies.

Spinal cord injury (SCI) is a disabling and destructive central nervous system injury that has not yet been successfully treated at this stage. Three-dimensional (3D) bioprinting has become a promising method to produce more biologically complex microstructures, which fabricate living neural constructs with anatomically accurate complex geometries and spatial distributions of neural stem cells, and this is critical in the treatment of SCI. With the development of 3D printing technology and the deepening of research, neural tissue engineering research using different printing methods, bio-inks, and cells to repair SCI has achieved certain results. Although satisfactory results have not yet been achieved, they have provided novel ideas for the clinical treatment of SCI. Considering the potential impact of 3D bioprinting technology on neural studies, this review focuses on 3D bioprinting methods widely used in SCI neural tissue engineering, and the latest technological applications of bioprinting of nerve tissues for the repair of SCI are discussed. In addition to introducing the recent progress, this work also describes the existing limitations and highlights emerging possibilities and future prospects in this field.

Objective:To evaluate the clinic efficacy of channel bone grafting [preservation of the sclerotic bone at the broken nonunion ends and fixation with limited contact dynamic compression plate (LC-DCP)] in the treatment of postoperative atrophic nonunion of middle clavicular fracture.Methods:The 41 patients were retrospectively analyzed who had been treated at Department of Orthopaedics and Traumatology, Xi'an Hong-Hui Hospital for atrophic nonunion after internal fixation of middle clavicular fracture from June 2015 to December 2019. They were 23 males and 18 females, with a mean age of 47.6 years (from 28 to 63 years). The left side was affected in 25 cases and the right side in 16 cases. The time interval between initial fracture surgery and nonunion surgery averaged 18.5 months (from 9 to 40 months). Thirty-six cases had undergone one operation and 5 cases 2 operations before admission. The length of bone defect was measured during operation. All nonunions were treated with construction of a graft channel, iliac bone graft and LC-DCP internal fixation above the clavicle. The upper limb function of the affected side was evaluated by the Disabilities of Arm, Shoulder and Hand (DASH) 12 months after operation.Results:The 41 patients were followed up for an average of 13.6 months (from 12 to 15 months). A bone defect ≤2.0 cm was found in 25 cases and that >2.0 cm in 16 ones. Nonunion healed in all patients after an average time of 14 weeks (from 12 to 16 weeks). One patient reported continuous pain in the donor area after operation and the other developed deep venous thrombosis at the right lower limb. The DASH upper limb scores at 12 months after operation averaged 14.7.Conclusion:Channel bone grafting is a feasible clinical treatment of postoperative atrophic nonunion of middle clavicular fracture, because it preserves the sclerotic bone at the broken nonunion ends, reduces the amount of iliac bone graft and leads to fine clinic efficacy.