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.

BackgroundMigraine is a common chronic neurological disease， and patent foramen ovale （PFO） has been closely associated with migraine. Current research primarily focuses on the pathological mechanism and the therapeutic effects of interventional closure， with limited attention paid to the impact of PFO on sleep quality in migraine patients. ObjectiveTo compare the difference in sleep quality between PFO-positive and PFO-negative migraine patients， and to analyzes influencing factors of sleep quality in PFO-positive migraine patients， so as to provide references for clinical interventions to improve sleep quality in PFO-positive migraine patients. MethodsA total of 673 migraine patients who met the diagnostic criteria of migraine in the International Classification of Headache Disorders， third edition （ICHD-3）， and all patients underwent contrast-enhanced transcranial Doppler （c-TCD） and transthoracic echocardiographic right heart contrast echocardiography （cTTE） in the Third Hospital of Mianyang from January 2020 to October 2024. Basic demographic data were collected using a self-designed questionnaire， headache severity was assessed with the Visual Analogue Scale （VAS）， and sleep quality was invaluated using the Pittsburgh Sleep Quality Index （PSQI）. PFO patients was diagnosed through c-TCD combined with c-TTE. Binary logistic regression analysis was employed to examine the influencing factors of sleep quality in PFO-positive migraine patients. ResultsA total of 673 （100.00%） migraine patients were enrolled， including 223 PFO-positive cases （33.14%） and 450 PFO-negative cases（66.86%）. The PFO-positive group showed significantly more severe headache severity （χ²=15.799， P<0.01） and poorer sleep quality （χ²=14.377， P<0.01） compared with PFO-negative group. PFO-positive patients demonstrated significantly higher barrier factor scores of sleep quality， sleep latency， sleep efficiency， sleep disturbance， hypnotic medication use， and daytime dysfunction compared with PFO-negative counterparts （t=3.634， 3.269， 2.785， 3.428， 2.907， 3.637， Bonferroni adjust P<0.05/7=0.007）.By contrast， no significant difference was noted in sleep duration scores between the two groups（t=2.349， Bonferroni adjust P>0.05/7=0.007）.The Binary Logistic regression analysis revealed that age （OR=1.021， 95% CI： 1.001~1.041）， headache severity （OR=6.030， 95% CI： 4.085~8.901）， and PFO grade （OR=1.893，95% CI： 1.288~2.784）were significant influencing factors for sleep quality in migraine patients with PFO. ConclusionMigraine patients with PFO-positive exhibited poorer sleep quality compared wtih PFO-negative patients. Older age， higher headache servity， and more severe PFO grade are identified as risk factors for impaired sleep quality in PFO-positive migraine patients.

Pyran- and furanocoumarins are key representatives of tetrahydropyrans and tetrahydrofurans, respectively, exhibiting diverse physiological and medical bioactivities. However, the biosynthetic mechanisms for their core structures remain poorly understood. Here we combined multiomics analyses of biosynthetic enzymes in Peucedanum praeruptorum and in vitro functional verification and identified two types of key enzymes critical for pyran and furan ring biosynthesis in plants. These included three distinct P. praeruptorum prenyltransferases (PpPT1-3) responsible for the prenylation of the simple coumarin skeleton 7 into linear or angular precursors, and two novel CYP450 cyclases (PpDC and PpOC) crucial for the cyclization of the linear/angular precursors into either tetrahydropyran or tetrahydrofuran scaffolds. Biochemical analyses of cyclases indicated that acid/base-assisted epoxide ring opening contributed to the enzyme-catalyzed tetrahydropyran and tetrahydrofuran ring refactoring. The possible acid/base-assisted catalytic mechanisms of the identified cyclases were theoretically investigated and assessed using site-specific mutagenesis. We identified two possible acidic amino acids Glu303 in PpDC and Asp301 in PpOC as vital in the catalytic process. This study provides new enzymatic tools in the epoxide formation/epoxide-opening mediated cascade reaction and exemplifies how plants become chemically diverse in terms of enzyme function and catalytic process.

ObjectiveTo evaluate the clinical efficacy and safety of Tongluo Mingmu capsules in the treatment of diabetic retinopathy with blood stasis， collateral obstruction， and Qi and Yin deficiency syndrome. MethodA randomized， double-blind， positive-control， and multi-center clinical trial design method was used. 416 patients with diabetic retinopathy with blood stasis， collateral obstruction， and Qi and Yin deficiency syndrome in four test centers were included （the ratio of the treatment group to the control group was 3∶1）. On the basis of standardized hypoglycemic treatment， the treatment group was given both four Tongluo Mingmu capsules and two Calcium Dobesilate capsule agents three times a day， while the control group were given both two Calcium Dobesilate capsules and four Tongluo Mingmu capsule agents three times a day. The course of treatment was 12 weeks. The curative effect of Tongluo Mingmu capsules was evaluated by comparing the comprehensive curative effect of diabetic retinopathy， traditional Chinese medicine（TCM） syndrome score， corrected visual acuity， fundus changes， fundus fluorescence angiography， and other curative effect indexes before and after treatment in the two groups. At the same time， general examination， laboratory examination， and adverse events were performed to evaluate the safety of the drug. ResultThe baseline demographic data and disease characteristics of the treatment group and the control group were balanced and comparable， with the difference not statistically significant. After 12 weeks of treatment， the total effective rate of the comprehensive curative effect of diabetic retinopathy in the treatment group （61.0%， 189/310） was better than that in the control group （44.1%， 45/102）， and the difference was statistically significant （χ²=8.880， P<0.01）. The total effective rate of TCM syndromes in the treatment group （88.4%， 259/293） was better than that in the control group （69.9%， 65/93）， and the difference was statistically significant （χ²=17.927， P<0.01）. The disappearance rate of dry eyes （χ²=8.305）， dull complexion （χ²=4.053）， lassitude （χ²=10.267）， shortness of breath （χ²=8.494）， and dry stool （χ²=8.657） in the treatment group was higher than that in the control group， and the difference between the groups was statistically significant （P<0.05， P<0.01）. In terms of improving corrected visual acuity （χ²=8.382）， fundus changes （χ²=6.026） ， the treatment group was significantly better than the control group （P<0.05）. During the trial， the incidence of adverse events in the treatment group and the control group was 1.3% and 2.9%， respectively. There was no significant difference between the two groups. In addition， there were no serious adverse events and adverse events leading to withdrawal in both groups. ConclusionTongluo Mingmu capsules can improve the comprehensive curative effect of diabetic retinopathy and enhance the efficacy of TCM syndromes， visual acuity， fundus changes， and fundus fluorescein angiography， with great safety. Therefore， it can provide a new alternative therapeutic drug for patients with diabetic retinopathy.

Objective:To conduct the genetic analysis of a family with one patient suffering from juvenile Parkinson's disease(JP)and discuss the clinical manifestations,genetic mutation characteristics,and treatment plans prompted by PRKN gene compound heterozygous mutations,and to enhance the clinicians'awareness of this disease.Methods:The clinical data of one patient with JP caused by PRKN gene mutations was analyzed,the clinical manifestations and genetic mutation features of the patient were summarized,and the related literatures were reviewed.Results:The patient,a 16-year-old male,was admitted to the hospital due to unstable gait,trembling limbs with rigidity in both lower limbs for three years.The examination results revealed a panic gait,clear consciousness,fluent speech,normal muscle strength in limbs,increased"gear-like"muscle tone in both upper limbs,and"lead-pipe"rigidity in both lower limbs;the sensory functions and tendon reflexes were normal.The head,neck,and thoracic magnetic resonance imaging(MRI)results showed no abnormalities.18F-fluorodeoxyglucose(18F-FDG)positron emission tomography/computed tomography(PET/CT)results showed that the head size and shape were normal,the glucose metabolism in the left cerebellum and middle temporal gyrus was slightly decreased,and the glucose metabolism in bilateral thalami,right frontal lobe,parietotemporal lobe,and left medial frontal lobe was increased.The dopamine transporter(DAT)PET/CT results showed that there was no radioactive distribution in the brain cortex and the DAT distribution in the posterior part of both striata was decreased.The whole-exome sequencing results showed the patient had two PRKN gene mutations,such as codons c.8T>A and c.850G>C compound heterozygous mutations,and each mutation was from one parent;the patient's father carried the c.8T>A mutation,the patient's mother carried the c.850G>C mutation,and the patient's sister had the same genetic mutation site as the patient's father.Conclusion:PRKN gene compound heterozygous mutations may be the basis of the disease in this family.Identification of the mutation c.8T>A expands the mutation spectrum of the PRKN gene,and provides the valuable information for the research on the pathogenic genetic mutations of the JP patients.

Objective:To evaluate direct and indirect costs for schizophrenia,major depressive disorder(MDD)and bipolar disorder,and to compare their differences of cost composition,and to explore the drivers of the total costs.Methods:A total of 3 175 inpatients with schizophrenia,MDD,and bipolar disorder were recruited.In-patient's self-report total direct of medical costs outpatient and inpatient,out-of-pocket costs,and direct non-medical costs were regarded as direct costs.Productivity loss and other loss caused by damaging properties were defined as indirect costs.The perspectives of this study included individual and societal levels.Multivariate regression analysis was applied for detecting the factors influencing disease costs.Results:The total cost of schizophrenia was higher than those of MDD and bipolar disorder at individual and societal levels.The indirect costs of three mental disorders were higher than the direct costs,and the indirect cost ratio of bipolar disorder was higher than those of schizophre-nia and MDD.Age,gender,working condition and marital status(P＜0.05)were the important drivers of total costs.Conclusion:The economic burden of the three mental disorders is relatively heavy.Schizophrenia has heaviest disease burden,and the productivity loss due to mental disorders is the driving force of the soaring disease cost

BACKGROUND:The threaded conical implant has a good ability to control micro movements and is conducive to immediate loading.However,the effects of double-threaded conical cylindrical implants and conical cylindrical implants on stress distribution and initial stability of implant-bone interface after immediate loading have not been reported. OBJECTIVE:To investigate the impact of double-threaded conical cylindrical implants and conical cylindrical implants on the biological distribution of the implant and the surrounding bone interface during immediate loading in the mandibular molar region. METHODS:(1)Three-dimensional finite element analysis:Conical beam CT scans of the mandible and first molar of a volunteer were used to develop a basal model of the mandible.The double-threaded conical cylindrical implants and conical cylindrical implants were assembled with the mandibular models,and an immediate-load(or delayed implantation)implant model(a total of four models)for the first mandibular molar was established.Loads in four directions(100 N):axial,lingual and buccal 45°,mesial and distal,and buccal and lingual,were applied to the central fossa of each model's crown.Three-dimensional finite element method was used to analyze the implant displacement and the stress distribution at the implant-bone interface.(2)In vitro experiment:With the assistance of the oral implant robot,the double-threaded conical cylindrical implants and conical cylindrical implants were implanted on the same artificial bone pieces,separately,and the immediate load model of immediate implant implantation(or delayed implantation)was established in vitro(a total of four groups of models).Osstell resonance frequency analyzer and SmartPeg sensor were used to measure the implant stability coefficient in four vertical directions:front,rear,left,and right measurements,evaluate the initial stability,and verify the finite element analysis results. RESULTS AND CONCLUSION:(1)The displacement difference between double-threaded conical cylindrical implants and conical cylindrical implants was small when the immediate loading of delayed implantation was applied,but the maximum stress value of conical cylindrical implant-bone interface was greater than that of double-threaded conical cylindrical implant-bone interface.When the immediate loading of immediate implantation was applied,the maximum stress value and the maximum displacement of bone around the implant appeared when the load was applied in mesiodistal direction.The stress value of the conical cylindrical implant reached 298.84 MPa and the maximum displacement was 0.31 mm,both of which were larger than that of the double-threaded conical cylindrical implant.(2)The results of in vitro experiments showed that the stability coefficient of the double-threaded conical cylindrical implant was greater than that of the conical cylindrical implant.(3)Compared with the conical cylindrical implant,the double-threaded conical cylindrical implant has higher initial stability under immediate loading,suggesting that the use of double-threaded conical cylindrical implant should be given priority in clinical immediate loading.

BACKGROUND:Temporomandibular joint osteoarthritis is a common oral disease with a high incidence.However,temporomandibular joint osteoarthritis is not easy to be detected in the early stage,and it is difficult to obtain clinical pathological specimens,so it is difficult to carry out related research.The application of digital 3D printing technology to animal models of Temporomandibular joint osteoarthritis increases the consistency of the animal models,thus promoting the study of temporomandibular joint osteoarthritis. OBJECTIVE:To establish a standardized animal model of temporomandibular joint osteoarthritis using novel digital technology. METHODS:According to the different modeling methods of unilateral anterior crossbite,30 female Sprague-Dawley rats were randomly divided into traditional model group,digital model group,and control group(n=10 per group).Cartilage specimens of the condyles were collected at 4 and 8 weeks after modeling.The apparent morphology was observed by stereoscopic microscope.The pathological morphology was observed by hematoxylin-eosin staining and Safranin O/fast green staining.Changes in the expression of interleukin-1β and tumor necrosis factor-α were observed by ELISA,and changes in the expression of aggrecan,type Ⅱ collagen and matrix metalloproteinase-13 were observed by immunohistochemical staining. RESULTS AND CONCLUSION:Different degrees of degeneration were observed in the digital and traditional model groups.The body mass of rats in both the model groups decreased during the 1st week after intervention and subsequently demonstrated growth trend and were significantly lower than that in the control group.The results of stereoscopic microscope showed that at 4 and 8 weeks after modeling,the deformation and defect degree of the digital model group was significantly higher than that of the traditional model group.At these two time points,the Osteoarthritis Research Society International scores of the digital model group and the traditional model group were higher than those of the control group,and the Osteoarthritis Research Society International score of the digital model group was higher than that of the traditional model group(P＜0.05).Histopathological observation showed that the modified Mankin score and Osteoarthritis Research Society International score of the two model groups were significantly higher than those of the control group of the same age at 4 and 8 weeks after modeling(P＜0.05).Immunohistochemical staining results showed that at two time points,compared with the control group of the same age,the expression of aggrecan and type Ⅱ collagen decreased in the traditional model group and the digital model group,while the expression of matrix metalloproteinase 13 increased(P＜0.05).ELISA results showed that the expression levels of inflammatory factors interleukin-1β and tumor necrosis factor-α in the traditional and digital model groups were higher than those in the control group at 8 weeks,and the expression levels of interleukin-1β and tumor necrosis factor-α in the digital model group were higher than those in the traditional model group(P＜0.05).To conclude,the personalized metal tube designed and produced by 3D printing technology can quickly guide the osteoarthritis-like lesions of the temporomandibular joint without repeated trial and adjustment,which is reproducible and suitable for promotion and application.

Brucellosis is a zoonotic infectious disease caused by Brucella infection. So far, animal to animal Brucellosis has not been eradicated, and there is a lack of safe and effective human vaccine. Therefore, "early, combined, sufficient, and full course" drug treatment remains an important strategy in the management of human Brucellosis. The goal of treating brucellosis is to alleviate and shorten the symptom period, reduce complications, relapses, and chronicity. At present, although antibiotic treatment is effective for most patients, there are still some patients who experience treatment failure or later recurrence, so the treatment strategy for brucellosis urgently needs to be optimized. This article elaborates on the treatment principles, clinical treatment status, and future development trends of brucellosis, in order to provide references for optimizing drug treatment methods for brucellosis.

[Objective] To Compare the effectiveness of conventional local anesthesia (CLA) and two-plane local anesthesia (TPLA) in percutaneous nephrolithotomy (PCNL) so as to provide reference for clinical selection of appropriate anesthetic methods. [Methods] Clinical data of 345 patients with renal or ureteral calculi who underwent PCNL under local infiltration anesthesia in our hospital during Jan.2013 and Dec.2023 were retrospectively analyzed.The patients were divided into CLA group (n=114) and TPLA group (n=231) according to anesthetic methods.The intraoperative visual analogue scale (VAS) score, stone-free rate and incidence of complications were compared between the two groups. [Results] There were no significant differences in the baseline data between the two groups (P>0.05). When the cutaneous and renal channels were established, the VAS score was lower in the TPLA group than in the CLA group [(3.2±0.5) vs. (3.8±0.4), P=0.023]. However, there was no significant difference in the VAS score during lithotripsy [(3.3±0.5) vs. (3.4±0.5), P=0.061]. There were no significant differences between the two groups in terms of operation time, stone-free rate, hemoglobin drop, postoperative hospital stay, and time to remove nephrostomy tube and DJ tube retention time (P>0.05). [Conclusion] Both CLA and TPLA can provide good analgesia in PCNL, but TPLA can significantly reduce the pain sensation when the cutaneous and renal channels are established.