Xanthine oxidase (XO) is an important therapeutic target for the treatment of hyperuricemia and gout. Based on the previously identified potent XO inhibitor 1, seventeen oxadiazoles and their ring-opening analogues were designed and synthesized via the bioisostere replacement strategy. Among them, compounds 2l, 2n, and 3b showed obvious XO inhibitory activity at the concentration of 10 μmol·L^-1, and compound 3b exhibited an IC₅₀ value of 1.45 μmol·L^-1.

Objective To observe the efficacy and safety of Morinda officinalis oligosaccharides in the continuation treatment of mild and moderate depression.Methods An open,single-arm,multi-center design was adopted in our study.Adult patients with mild and moderate depression who had received acute treatment of Morinda officinalis oligosaccharides were enrolled and continue to receive Morinda officinalis oligosaccharides capsules for 24 weeks,the dose remained unchanged during continuation treatment.The remission rate,recurrence rate,recurrence time,and the change from baseline to endpoint of Hamilton Depression Scale(HAMD),Hamilton Anxiety Scale(HAMA),Clinical Global Impression-Severity(CGI-S)and Arizona Sexual Experience Scale(ASEX)were evaluated.The incidence of treatment-related adverse events was reported.Results The scores of HAMD-17 at baseline and after treatment were 6.60±1.87 and 5.85±4.18,scores of HAMA were 6.36±3.02 and 4.93±3.09,scores of CGI-S were 1.49±0.56 and 1.29±0.81,scores of ASEX were 15.92±4.72 and 15.57±5.26,with significant difference(P＜0.05).After continuation treatment,the remission rate was 54.59％(202 cases/370 cases),and the recurrence rate was 6.49％(24 cases/370 cases),the recurrence time was(64.67±42.47)days.The incidence of treatment-related adverse events was 15.35％(64 cases/417 cases).Conclusion Morinda officinalis oligosaccharides capsules can be effectively used for the continuation treatment of mild and moderate depression,and are well tolerated and safe.

BACKGROUND:Prosthesis loosening and wear are still the main problems in the failure of total ankle replacement,which are closely related to the micro-motion of the implant-bone interface,the contact stress of the articular surface and joint motion.The design of artificial joint components,including insert and tibial/talar stem prosthesis,is a key factor affecting the force,motion,and micromotion of the contact interface of the ankle joint.The development of new inserts is of great significance to improve the survival rate of artificial ankle joints. OBJECTIVE:The finite element model of the total ankle replacement model was constructed to detect the biomechanical properties of the porous structure-optimized inserts,and the effect of the porous structure-optimized inserts on reducing prosthesis micromotion and improving the contact behavior of the articular surface was analyzed. METHODS:Based on the CT scan data of the right ankle joint of a healthy adult and the INBONE Ⅱ system product manual,a three-dimensional model including bone and artificial joint system was established,and the total ankle replacement model(model A)was obtained after osteotomy and prosthesis installation,and then through four new types of inserts,G50,G60,D50,and D60,were obtained by transforming the porous structure of the original insert,and the original one was replaced with different inserts to establish an optimized total ankle replacement model(models B-E)corresponding to the inserts.The gait loads were applied on the five models to simulate the gait conditions.The differences in micromotion and articular surface contact behaviors at the implant-bone interface of all five models were compared. RESULTS AND CONCLUSION:(1)In the gait cycle,the micromotion of the prosthesis of the four optimized total ankle replacement models was lower than that of the original model.Compared with model A,the micromotion of the prosthesis in models B-E decreased by 5.4%,10.1%,8.1%,and 20.9%,respectively.The high micromotion area of t ??he tibial groove dome in the optimized model was significantly smaller than that of the original model.(2)The four optimized models obtained a larger articular surface contact area.Compared with model A,the average contact area of t ??he inserts in models B-E increased by 11.8%,14.7%,8.1%,and 32.6%,respectively.(3)Similar to the effect of increasing the contact area,compared with the original model,the contact stress of the optimized model decreased in varying degrees,and the value of model E decreased the most significantly(P<0.05),it is due to good mechanical properties and large porosity of the Diamond lattice that constitutes the D60-type insert.(4)The research results show that the use of porous structure to improve the inserts can improve the elasticity of the inserts and increase its ability to absorb joint impact,for favorable conditions are created for reducing micromotion at the implant-bone interface and improving joint contact behavior.

Aim To investigate the effect of quercetin on the aging model of bone marrow mesenchymal stem cells established under microgravity. Methods Using 3D gyroscope, a aging model of bone marrow mesenchymal stem cells was constructed, and after receiving quercetin and microgravity treatment, the anti-aging effect of the quercetin was evaluated by detecting related proteins and oxidation indexes. Results Compared to the control group, the expressions of age-related proteins p21, pi6, p53 and RB in the microgravity group significantly increased, while the expressions of cyclin D1 and lamin B1 significantly decreased, with statistical significance (P<0.05). In the microgravity group, mitochondrial membrane potential significantly decreased (P<0.05), ROS accumulation significantly increased (P <0.05), SOD content significantly decreased and MDA content significantly increased (P<0.05). Compared to the microgravity group, the expressions of age-related proteins p21, pi6, p53 and RB in the quercetin group significantly decreased, while the expressions of cyclin D1 and lamin B1 significantly increased, with statistical significance (P<0.05). In the quercetin group, mitochondrial membrane potential significantly increased (P<0.05), ROS accumulation significantly decreased (P<0.05), SOD content significantly increased and MDA content significantly decreased (P<0.05). Conclusions Quercetin can resist oxidation, protect mitochondrial function and normal cell cycle, thus delaying the aging of bone marrow mesenchymal stem cells induced by microgravity.

Aim To explore the impacts of high mobility group box 1 (HMGB1) on the phenotypes, endocy-tosis and extracellular signal-regulated kinase (ERK)/ Jun N-terminal protein kinase (JNK)/P38 mitogen-ac-tivated protein kinase (MAPK) signaling pathway in indoxyl sulfate (IS) -induced dendritic cells (DCs). Methods After treatment with 30, 300 and 600 (xmol · L

Tinnitus is a clinically refractory disease with a high incidence.LAI's Tongyuan acupuncture method believes that tinnitus is nothing more than the two ends of deficiency and excess.The deficiency is closely related to original spirit,and the excess is related to the pathological factors such as externally-contracted six pathogenic factors,phlegm-damp and blood stasis,and qi stagnation and yang constraint.The Tongyuan acupuncture method is based on original spirit,takes the two vessels of conception vessel(CV)and governor vessel(GV)as the general outline,takes the regulation of yin and yang as the main method,pays attention to the combination of local and overall,and emphasizes the application of tonification and purgation,and has the clinical effect of reinforcing healthy qi and dispelling pathogen,cultivating the vital essence.In clinical application,the method of'unblocking governor vessel and nourishing spirit'is used to play the role of heart and brain nourishing spirit and warming and supporting yang qi.The method of'conducting qi back to its source'has the effect of cultivating the vital essence and regulating qi movement.The treatments should be cooperated according to the syndromes,so that the pathogens can be expelled and healthy qi can be settled.Qi and blood have origins of generation and transformation and normally nourishing in the ear,so as to effectively alleviate the patient's tinnitus symptoms.This paper summarizes and analyzes Professor LAI Xin-Sheng's Experience in the diagnosis and treatment of tinnitus by Tongyuan acupuncture method,and provides a new acupuncture treatment plan for clinical application.

Objective To investigate the clinical characteristics and prognosis of pneumococcal meningitis(PM),and drug sensitivity of Streptococcus pneumoniae(SP)isolates in Chinese children.Methods A retrospective analysis was conducted on clinical information,laboratory data,and microbiological data of 160 hospitalized children under 15 years old with PM from January 2019 to December 2020 in 33 tertiary hospitals across the country.Results Among the 160 children with PM,there were 103 males and 57 females.The age ranged from 15 days to 15 years,with 109 cases(68.1% )aged 3 months to under 3 years.SP strains were isolated from 95 cases(59.4% )in cerebrospinal fluid cultures and from 57 cases(35.6% )in blood cultures.The positive rates of SP detection by cerebrospinal fluid metagenomic next-generation sequencing and cerebrospinal fluid SP antigen testing were 40% (35/87)and 27% (21/78),respectively.Fifty-five cases(34.4% )had one or more risk factors for purulent meningitis,113 cases(70.6% )had one or more extra-cranial infectious foci,and 18 cases(11.3% )had underlying diseases.The most common clinical symptoms were fever(147 cases,91.9% ),followed by lethargy(98 cases,61.3% )and vomiting(61 cases,38.1% ).Sixty-nine cases(43.1% )experienced intracranial complications during hospitalization,with subdural effusion and/or empyema being the most common complication[43 cases(26.9% )],followed by hydrocephalus in 24 cases(15.0% ),brain abscess in 23 cases(14.4% ),and cerebral hemorrhage in 8 cases(5.0% ).Subdural effusion and/or empyema and hydrocephalus mainly occurred in children under 1 year old,with rates of 91% (39/43)and 83% (20/24),respectively.SP strains exhibited complete sensitivity to vancomycin(100% ,75/75),linezolid(100% ,56/56),and meropenem(100% ,6/6).High sensitivity rates were also observed for levofloxacin(81% ,22/27),moxifloxacin(82% ,14/17),rifampicin(96% ,25/26),and chloramphenicol(91% ,21/23).However,low sensitivity rates were found for penicillin(16% ,11/68)and clindamycin(6% ,1/17),and SP strains were completely resistant to erythromycin(100% ,31/31).The rates of discharge with cure and improvement were 22.5% (36/160)and 66.2% (106/160),respectively,while 18 cases(11.3% )had adverse outcomes.Conclusions Pediatric PM is more common in children aged 3 months to under 3 years.Intracranial complications are more frequently observed in children under 1 year old.Fever is the most common clinical manifestation of PM,and subdural effusion/emphysema and hydrocephalus are the most frequent complications.Non-culture detection methods for cerebrospinal fluid can improve pathogen detection rates.Adverse outcomes can be noted in more than 10% of PM cases.SP strains are high sensitivity to vancomycin,linezolid,meropenem,levofloxacin,moxifloxacin,rifampicin,and chloramphenicol.[Chinese Journal of Contemporary Pediatrics,2024,26(2):131-138]

To evaluate the effectiveness and safety of implantable D-shant atrial shunt device in patients with severe pulmonary arterial hypertension(PAH)and right heart failure.A 53-year-old female patient diagnosed with severe idiopathic PAH and right heart failure,her WHO FC grade was Ⅳ.The right heart catheter and implantation of D-shant atrial shunt device were performed under local anesthesia on November 30,2021.A 6 mm×4 cm peripheral artery balloon was selected to dilate the atrial septum and a D-shant atrial shunt device with a fixed 4 mm diameter orifice was implanted into the heart.The clinical symptoms and hemodynamics of the patient was improved after the intervention.Implantation of atrial shunt device as a palliative therapy to established a right to left shunt is another strategy for treating patients with severe PAH in late period,which has good effectiveness and safety.It could be the last replacement therapy to improve symptoms and prolonged lives to drug resistant and severe PAH patients.

DPP4 is a serine exopeptidase that is immobilized on the cell membrane and plays a crucial regulatory role in various physiological and pathological activities within the human body.In addition to acting as a transcription factor to regulate the tran-scription and expression of downstream target genes,DPP4 also functions as a transcription-independent regulator through pro-tein-protein interactions.In recent studies,DPP4 has been strongly linked to various diseases,and several substances with the potential to target DPP4 have been identified.This paper mainly reviews the multifunctionality of DPP4 in regulating vari-ous aspects of energy metabolism,inflammation,tissue repair and carcinogenesis in the body.It also reviews the screening of in vitro inhibitors of DPP4 and its research progress in regulating chronic liver disease,based on the pathological development process of chronic liver disease.

navirus disease 2019 (COVID-19) in the patients younger than 18 years old infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant, and to provide a basis for determining the chest CT changes and efficacy of COVID-19 caused by Omicron virus variant in patients younger than 18 years old. Methods　The clinical and imaging data of 30 cases of patients younger than 18 years old infected with COVID-19 Omicron variant, who admitted to the Third People's Hospital of Shenzhen from February 11 to March 26, 2022 were collected and retrospectively analyzed. The clinical manifestations, imaging features and dynamic changes of lesions were summarized. Results A total of 41 intrapulmonary lesions in 30 patients with COVID-19 caused by SARS-CoV-2 Omicron variant. The main manifestations were patchy or nodular ground-glass opacities and/or consolidation, with focal subpleural distribution, lesions mainly occur in the right lung (70.73%, 29/41). There were 42 lesion morphologies, with 22 (52.38%) striped shadows and 16 (38.10%) nodular shadows, with small lamellar and patchy shadows predominating. There were 36 lesion density variations, with ground glass shadows being the most common, with a total of 24 ground glass shadows (66.66%) in each lobe of the lung, and also 6 consolidation lesions (16.67%) and 6 mixed ground glass opacity and consolidation lesions (16.67%). With the progression of the disease, lesions gradually enlarged, appeared on the 2nd day (312.93 mm3), peaked on the 9th day (1 837.18 mm3). The average absorption time of the lesions was (16±3) days, and there was no significant difference between the absorption time of patchy and nodular lesions (ground glass and/or consolidation) (t=0.853, P>0.05). The lesions showed focal ground-glass opacity in the early stage, 77.78% lesions were absorbed after treatment in the late stage. Inflammatory nodules were absorbed slowly (9-19 days), without residual fibrotic changes. Conclusions　The imaging manifestations of COVID-19 in patients younger than 18 years old infected with SARS-CoV-2 Omicron variant have certain characteristics, showed patchy or nodular ground glass opacities and/or consolidation, mainly distributed in the subpleural area, with small and few lesions and slow change, didn't remain fibrosis. Being familiar with its clinical and imaging manifestations can assist in early diagnosis, but confirming the diagnosis requires a combination of epidemiological history, clinical symptoms, SARS-CoV-2 nucleic acid and radiological manifestations.