Six compounds were isolated from the ethyl acetate fraction of Citri Sarcodactylis Fructus by using various column chromatographic methods, such as MCI Gel CHP-20, ODS, Sephadex LH-20, silica gel and semipreparative HPLC. Their structures were identified to be citrusin G (1), citrusin H (2), citrusin E (3), syringin (4), coniferin (5), methylconiferin (6) by NMR, HR-ESI-MS, UV, IR spectra. Compounds 1 and 2 were new secondary metabolism products and 3-6 were obtained from the titled material for the first time. Compound 1 showed anti-renal fibrosis activity in TGF-β1-induced kidney proximal tubular cells.

OBJECTIVES: To study clinical manifestations and gene mutation features of neonates with centronuclear myopathy. METHODS: A retrospective analysis was conducted on the medical data of 5 neonates with centronuclear myopathy diagnosed in the Neonatal Intensive Care Unit of Children's Hospital, Zhejiang University School of Medicine from January 2020 to August 2024. The data included gender, gestational age, birth weight, Apgar score, clinical manifestations, creatine kinase level, electromyography, genetic testing results and the outcomes of the infants. RESULTS: All 5 male neonates had a history of postpartum asphyxia and resuscitation. They all presented with hypotonia, myasthenia, and respiratory failure; two neonates also had swallowing dysfunction. Of the five neonates, three had normal creatine kinase levels, while two had slightly elevated levels. Electromyography was performed for three neonates, among whom two had myogenic damage. MTM1 gene mutations were identified by genetic testing in all five neonates, including two nonsense mutations and three missense mutations, among which one variant had not been previously reported. Four mutations were inherited from the mother, and the other one was a de novo mutation. The five neonates showed no clinical improvement following treatment, failed weaning from mechanical ventilation, and ultimately died after withdrawal of life-sustaining therapy. CONCLUSIONS Centronuclear myopathy caused by MTM1 gene mutation often has a severe phenotype and a poor prognosis, and it should be considered for neonates with hypotonia and myasthenia after birth. Genetic testing should be performed as soon as possible.
Humans ; Myopathies, Structural, Congenital/genetics* ; Male ; Infant, Newborn ; Retrospective Studies ; Mutation ; Female ; Protein Tyrosine Phosphatases, Non-Receptor/genetics*

OBJECTIVE: To explore the synergistic effect of flumatinib (FLU) combined with histone deacetylase inhibitor chidamide (CHI) and underlying mechanism on Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph⁺ ALL) SUP-B15 cells. METHODS: CCK-8 method was used to examine the effects of FLU, CHI alone and combination therapy on the proliferation of SUP-B15 cells. Flow cytometry was utilized to analyze the cell cycle and apoptosis. RT-qPCR and Western blot methods were performed to detect target gene expression. RESULTS: FLU combined with CHI significantly inhibited the proliferation, induced G₀/G₁ phase arrest, and increased the apoptosis rate in SUP-B15 cells compared with FLU and CHI alone. The 50 genes were identified by overlapping the two drugs' targets of action with Ph⁺ ALL oncogenic genes in the public databases, and p53 and c-Myc transcription factors and PI3K/AKT signaling pathways were enriched in the overlapped genes. The combination of FLU and CHI significantly reduced the mRNA level of BCR::ABL fusion gene, up-regulated the protein and mRNA levels of p53, BAX, and Caspase-3, and down-regulated the protein and mRNA levels of c-Myc, PIK3CA, PIK3CB, and AKT2 compared with single-drug therapy. The analysis of GEO database and our center cohort showed that c-Myc, PIK3CA, PIK3CB, and AKT2 were significantly up-regulated while p53 was down-regulated in Ph⁺ ALL patients compared to healthy controls. CONCLUSION FLU combined with CHI synergistically inhibits cell proliferation, promotes apoptosis, and induces cycle arrest by targeting the PI3K/AKT signaling pathway through the p53/c-Myc axis in Ph⁺ ALL.
Humans ; Aminopyridines/pharmacology* ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy* ; Apoptosis/drug effects* ; Benzamides/pharmacology* ; Cell Proliferation/drug effects* ; Philadelphia Chromosome ; Drug Synergism ; Cell Line, Tumor ; Signal Transduction ; Pyridines/pharmacology* ; Phosphatidylinositol 3-Kinases/metabolism*

Temporal interference (TI) is a form of stimulation that epitomizes an innovative and non-invasive approach for profound neuromodulation of the brain, a technique that has been validated in mice. Yet, the thin cranial bone structure of mice has a marginal influence on the effect of the TI technique and may not effectively showcase its effectiveness in larger animals. Based on this, we carried out TI stimulation experiments on rats. Following the TI intervention, analysis of electrophysiological data and immunofluorescence staining indicated the generation of a stimulation focus within the nucleus accumbens (depth, 8.5 mm) in rats. Our findings affirm the viability of the TI methodology in the presence of thick cranial bones, furnishing efficacious parameters for profound stimulation with TI administered under such conditions. This experiment not only sheds light on the intervention effects of TI deep in the brain but also furnishes robust evidence in support of its prospective clinical utility.
Animals ; Deep Brain Stimulation/methods* ; Nucleus Accumbens/physiology* ; Male ; Rats ; Rats, Sprague-Dawley ; Time Factors

Cemental tear is a rare and indetectable condition unless obvious clinical signs present with the involvement of surrounding periodontal and periapical tissues. Due to its clinical manifestations similar to common dental issues, such as vertical root fracture, primary endodontic diseases, and periodontal diseases, as well as the low awareness of cemental tear for clinicians, misdiagnosis often occurs. The critical principle for cemental tear treatment is to remove torn fragments, and overlooking fragments leads to futile therapy, which could deteriorate the conditions of the affected teeth. Therefore, accurate diagnosis and subsequent appropriate interventions are vital for managing cemental tear. Novel diagnostic tools, including cone-beam computed tomography (CBCT), microscopes, and enamel matrix derivatives, have improved early detection and management, enhancing tooth retention. The implementation of standardized diagnostic criteria and treatment protocols, combined with improved clinical awareness among dental professionals, serves to mitigate risks of diagnostic errors and suboptimal therapeutic interventions. This expert consensus reviewed the epidemiology, pathogenesis, potential predisposing factors, clinical manifestations, diagnosis, differential diagnosis, treatment, and prognosis of cemental tear, aiming to provide a clinical guideline and facilitate clinicians to have a better understanding of cemental tear.
Humans ; Dental Cementum/injuries* ; Consensus ; Diagnosis, Differential ; Cone-Beam Computed Tomography ; Tooth Fractures/therapy*

With the growing emphasis on maternal and child oral health, the significance of managing oral health across preconception, pregnancy, and infancy stages has become increasingly apparent. Oral health challenges extend beyond affecting maternal well-being, exerting profound influences on fetal and neonatal oral development as well as immune system maturation. This expert consensus paper, developed using a modified Delphi method, reviews current research and provides recommendations on maternal and child oral health management. It underscores the critical role of comprehensive oral assessments prior to conception, diligent oral health management throughout pregnancy, and meticulous oral hygiene practices during infancy. Effective strategies should be seamlessly integrated across the life course, encompassing preconception oral assessments, systematic dental care during pregnancy, and routine infant oral hygiene. Collaborative efforts among pediatric dentists, maternal and child health workers, and obstetricians are crucial to improving outcomes and fostering clinical research, contributing to evidence-based health management strategies.
Humans ; Pregnancy ; Female ; Infant ; Consensus ; Mouth Diseases/therapy* ; Pregnancy Complications/therapy* ; Oral Health ; Infant, Newborn ; Delphi Technique ; Oral Hygiene

Purpose To analyze the impact of clinicopatho-logical factors on residual tumor burden(RCB)grading system and Miller-Payne(MP)grading system in non-specific invasive breast cancer patients after neoadjuvant chemotherapy,and to explore the predictive value of the two grading systems for patient survival.Methods The clinical data of 177 patients with non-specific invasive breast cancer diagnosed by preoperative punc-ture and treated with neoadjuvant chemotherapy were retrospec-tively analyzed.The relationship of RCB grading system or MP grading system with disease free survival(DFS)and overall sur-vival(OS)was studied,and the value of the two systems in predicting prognosis was analyzed and compared.Results RCB grading was related to menstrual status,histological grading be-fore treatment,and lymph node metastasis after treatment;MP grading was related to pre-treatment histological grading,post-treatment lymph node metastasis,and pre-treatment molecular typing.By evaluating the ROC curve of recurrence and survival and comparing the area under curve(AUC),it was shown that RCB grading system was superior to MP grading system in pre-dicting recurrence and evaluating survival.Univariate and multi-variate survival analysis showed that pre-treatment clinical stag-ing,post-treatment lymph node metastasis,and RCB grading were independent factors for DFS.Pre-treatment clinical stag-ing,pre-treatment molecular typing,and RCB grading were in-dependent factors for OS,while MP grading was not an inde-pendent factor for DFS and OS.Conclusion RCB grading sys-tem has a higher predictive value for patient survival than MP grading system.RCB grading evaluation system is recommended as evaluation system for non-specific invasive breast cancer after neoadjuvant chemotherapy.

Odontogenic maxillary sinusitis(OMS)is a subtype of maxillary sinusitis(MS).It is actually inflammation of the maxillary sinus that secondary to adjacent infectious maxillary dental lesion.Due to the lack of unique clinical features,OMS is difficult to distinguish from other types of rhinosinusitis.Besides,the characteristic infectious pathogeny of OMS makes it is resistant to conventional therapies of rhinosinusitis.Its current diagnosis and treatment are thus facing great difficulties.The multi-disciplinary cooperation between otolaryngologists and dentists is absolutely urgent to settle these questions and to acquire standardized diagnostic and treatment regimen for OMS.However,this disease has actually received little attention and has been underrepresented by relatively low publication volume and quality.Based on systematically reviewed literature and practical experiences of expert members,our consensus focuses on characteristics,symptoms,classification and diagnosis of OMS,and further put forward multi-disciplinary treatment decisions for OMS,as well as the common treatment complications and relative managements.This consensus aims to increase attention to OMS,and optimize the clinical diagnosis and decision-making of OMS,which finally provides evidence-based options for OMS clinical management.

Objective:To evaluate the diagnostic value of hematological parameters for PCa with prostate-specific antigen(PSA)of 4-10 μg/L and construct a risk-stratification model with these parameters.Methods:We retrospectively analyzed the da-ta on the males undergoing the initial prostatic biopsy in the Affiliated Hospital of Xuzhou Medical University with PSA of 4-10 μg/L from March 2010 to April 2021.According to the results of biopsy,we classified the patients into a PCa and a non-PCa group,and compared the hematological parameters between the two groups.We performed univariate and multivariate logistic regression analyses,identified the independent risk factors for PCa,constructed a risk-stratification model for the prediction of PCa and evaluated its effi-ciency.Results:A total of 415 cases were included in this study,107(25.8％)in the PCa and 308(74.2％)in the non-PCa group.Compared with the non-PCa males,the PCa patients showed a significantly older age,higher ratios of neutrophil to lymphocyte and platelet to lymphocyte,systemic immune-inflammation index(SII),red blood cell distribution width and cystatin C(CysC)level(all P＜0.05),but lower red blood cell count and hemoglobin and free/total PSA(f/tPSA)levels(all P＜0.05).Multivariate logis-tic regression analysis indicated that age,f/tPSA,SII and CysC were independent risk factors for the prediction of PCa(all P＜0.05).Five prediction models were constructed based on the above risk factors,and the area under the ROC curve(AUC)of the four-parameter(age+f/tPSA+SII+CysC)model was 0.745(95％CI:0.694-0.796),significantly higher than those of the other mod-els(P＜0.05).A risk-stratification model(low-,intermediate-,and high-risk)was also constructed based on the total nomogram scores,which showed a comparable performance to that of the Prostate Imaging Reporting and Data System(PI-RADS)for the predic-tion of PCa(AUC:0.727[95％CI:0.650-0.804]vs 0.734[95％CI:0.658-0.811]).However,the prediction rate by the risk-stratification model was evidently higher in the low-risk males than in those with low PI-RADS scores(1-2)(39.4％vs 22.2％).Conclusion:SII and CysC are independent risk factors for the prediction of PCa in patients with gray-zone PSA levels.The risk-stratification model based on age,SII,CysC and f/tPSA is comparable to PI-RADS in the diagnostic efficiency of PCa,with an even higher prediction rate in low-risk patients than in those with low PI-RADS scores,and contributive to precision screening and reduction of excessive biopsies in the diagnosis of PCa with gray-zone PSA.

OBJECTIVE: To analyze the safety and effectiveness of 3D printing prefabricated nail path model assisted lumbosacral hemivertebra orthopaedic surgery. METHODS: A retrospective analysis was performed on 8 patients with lumbosacral hemivertebra deformity admitted from January 2016 to July 2021, including 3 males and 5 females, aged 6 to 15 at the time of surgery. The hemivertebra of 4 cases located on the left side and 4 cases on the right side. The hemivertebra of 1 case located at L_2,3, 2 cases at L_3,4, 2 cases at L_4,5, and 3 cases at L₅S₁. Four cases were fully segmented hemivertebra and 4 cases were incomplete segmented hemivertebra. The patient CT data was imported into Mimics 21.0 software for modeling, and then the model data was imported into 3-Matic software. The vertebra requiring screw placement was selected to simulate the optimal screw placement angle and length, and the model was printed for preoperative planning and intraoperative guidance. All patients underwent orthopedic surgery with the aid of 3D printing preset nail path model. The safety and effectiveness of the 3D printing prefabricated nail tunnel model assisted lumbosacral hemivertebra orthopaedic surgery was evaluated by comparing the imaging parameters of the patients. The main outcome measures were the Cobb angle of the main curve, the Cobb angle of the proximal compensatory curve, the coronal balance index C₇ plumb line-center sacral vertical line(C₇PL-CSVL), the accuracy of nail placement, and the correction rate of scoliosis before surgery, 1 week and 1 year after surgery. RESULTS: All of 8 patients were followed up for 13 to 31 months. A total of 98 pedicle screws were placed in 8 patients. The number of pedicle screw grades A, B, C, D, E was 38, 46, 10, 4, 0 screws. The screws of grade A and B were defined as good position, the accuracy rate of screw placement was 85.7%. The Cobb angle of the main curve were 21° to 38° before operation, 5° to 11° at 1 week after operation, 7°to 12° at 1 year after operation. The Cobb angle of the proximal compensatory curve were 16° to 39° befoer operation, 7° to 12 °at 1 week after operation, 7° to 14° at 1 year after operation, the correction effect remained good with no correction loss. The coronal balance index C7PL-CSVL were 20 to 35 mm before operation, 11 to 18 mm at 1 week after operation, 10 to 16 mm at 1 year after operation, the coronal imbalance improved. The scoliosis correction rate was 65.6% to 84.2% 1 week after surgery, and 61.9% to 81.6% 1 year after surgery. CONCLUSION The use of 3D printing prefixed nail tunnel model in lumbosacral hemivertebra osteotomy is safe and effective, and can significantly improve patients' local deformities. It is a reliable method to assist lumbar sacral hemivertebra osteotomy.
Humans ; Printing, Three-Dimensional ; Female ; Male ; Adolescent ; Retrospective Studies ; Child ; Lumbar Vertebrae/surgery* ; Sacrum/abnormalities* ; Bone Nails ; Orthopedic Procedures/instrumentation*