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 Mobile artificial lumbar complex(MALC)which suitable for reconstruction after subtotal lumbar resection in goats was developed,and to test stability of the complex and postoperative lumbar segmental motor function.Methods Eighteen male boer goats aged from 1 to 2 years old(weighted from 35 to 45 kg)were selected and divided into con-trol group,fusion group and non-fusion group,with 6 goats in each group.According to preoperative CT scans and MRI exami-nations of lumbar,the goat MALC was designed and performed by 3D printed for non-fusion group.Operation was performed on three groups respectively,and only vertebral body and disc were exposed in control group.In fusion group,L4 part of vertebral body and the upper and lower complete disc tissues were removed,and the lumbar spine bone plate fixation was performed with titanium mesh bone grafting.In non-fusion group,vertebral body and disc were removed in the same way,and MALC was im-planted.AP and lateral X-rays of lumbar vertebrae in goat were taken at 6 months after surgery,in order to understand whether the plant was dislocated,displaced and fractured.Biomechanical tests were performed on the specimens by mechanical instru-ment to measure range of motion(ROM)of L2,3,L,4,L4,5intervertebral space and the overall ROM of L2-5 lumbar vertebrae.Results MALC of lumbar vertebra was designed by 3D printing,and its component artificial vertebrae and upper and lower ar-tificial end plates were manufactured.The semi-spherical structure was fabricated by precision lathe using high-crosslinked polyethylene material,and the prosthesis was assembled.Postoperative AP and lateral X-rays of lumbar vertebra at 6 months showed the implant position of implant and MALC were good without displacement and dislocation.In vitro biomechanical test of lumbar vertebrae specimens:(1)There were no statistical significance in ROM of lumbar intervertebral space flexion and extension,lateral flexion and rotation on L.4 and L4,5,between non-fusion group and control group(P＞0.05),while ROM of fu-sion group was significantly reduced compared with the other two groups(P＜0.05).There were no significant difference in ROM of L2.3 intervertebral flexion and extension,lateral flexion and rotation between non-fusion group and control group(P＞0.05),while fusion group was significantly increased compared with the other two groups(P＜0.001).(2)There was no signifi-cant difference in overall lumbar ROM of L2-5(P＞0.05).Conclusion The individual MALC could restore intervertebral height of lumbar vertebra while maintaining the stability of lumbar vertebra and re-establishing motor function of lumbar space.

Objective To investigate the mid-term effect and complications of arthroscopic popliteal tendon suture in the treatment of lateral meniscus injury.Methods From January 2016 to December 2020,the data of 57 patients with lateral meniscus popliteal tendon injury treated by arthroscopic popliteal tendon suture fixation were retrospectively analyzed,includ-ing 35 males and 22 females,aged from 18 to 47 years old with an average of(32.9±7.9)years old.Knee function was evaluat-ed using the International Knee Documentation Committee(IKDC)and Lysholm scores both before the operation and at the fi-nal follow-up.Meniscus healing was evaluated according to the postoperative Barrett standard.Wound healing complications,such as vascular injury,nerve injury,and lower extremity venous thrombosis,were recorded.Results All 57 patients were fol-lowed up for 12 to 58 months with an average of(38.1±14.9)months.The incisions of the patients after the operation were all Grade A healing without infection,popliteal tendon injury,blood vessel injury,nerve injury and lower extremity venous throm-bosis.The IKDC score increased from(49.7±3.6)points preoperatively to(88.5±4.4)points in the final follow-up(P＜0.05).The Lysholm score increased from(48.8±4.9)points preoperatively to(91.9±3.9)points at the final follow-up(P＜0.05).At 3,6 months and 1 year after operation,according to Barrett's criteria,54 cases were clinically healed,the healing rate was 94.7％(54/57).Conclusion This study preliminarily confirmed that arthroscopic suture technique can result in clinical sta-bility through suture and fixation of the meniscus in the injured lateral popliteal tendon area.No adverse effects on knee joint function were found in the mid-term follow-up after the operation.

Objective To compare the clinical efficacy of the posterior hemipelvectomy of the greater trochanter approach with the standard Kocher-Langenbeck(K-L)approach in the treatment of posterior acetabulum wall fractures and to explore a more optimal approach for the treatment of posterior acetabulum wall fractures.Methods Total of 26 patients with posterior ac-etabulum wall fractures were retrospectively analysed and divided into two groups:the posterior hemipelvectomy of the greater trochanter group(test group)and the standard K-L approach group(control group).In the test group,there were 24 patients including 16 males and 8 females with an average age of(42.00±4.52)years old,the time of injury to surgery was(6.75±1.15)d.In the control group,there were 23 patients including 16 males and 7 females with an average age of(41.00±5.82)years old,the time of injury to surgery was(7.09±1.20)days.The total hospital stay,length of incision,operation time,intraoperative bleeding,postoperative drainage,discharge,fracture reduction quality(Matta criteria),hip abduction muscle strength,hip func-tion(Merle d'Aubigne-Postel score),postoperative complications and the incidence of ectopic ossification were compared.Results All cases were followed up for 6 months.There was no significant difference in incision length,intraoperative bleeding and postoperative drainage between two groups(P＞0.05).However,the operation time of the test group was shorter than that of the control group(P＜0.05).There was no statistically significant difference in fracture reduction and hip function between two groups(P＞0.05).The hip abduction muscle strength of test group was better than that of control group(P＜0.05).In addition,there was no significant difference in the incidence of postoperative complications and heterotopic ossification between two groups(P＞0.05).Conclusion Compared with the standard K-L approach,the posterior hemipelvectomy of the greater trochanter approach can shorten the operative time,has better recovery of the postoperative hip abduction muscle strength,ex-poses the view of the fracture involving the more comminuted posterior acetabulum wall or the fracture of the roof of the socket,improved the rate of fracture anatomical repositioning,provides a new idea for the clinical treatment of posterior acetabulum wall fractures,and allows patients to perform functional exercises at an early stage.

Mitral annular calcification(MAC)is an age-related,chronic,degenerative change in localized fibrous support structures,and current research suggests that it is a process similar to the active onset of atherosclerosis and aortic valve calcification,both of which are accompanied by the deposition of lipoprotein(α)[Lp(α)]and the formation of chronic inflammatory foci.Among them,Lp(α)is the hot spot of research.In recent years,the relationship between Lp(α)and aortic valve calcification has received extensive attention.A large number of studies have demonstrated that elevated Lp(α)and its associated oxidized phospholipids(OxPL)can promote aortic valve calcification and stenosis through multiple calcium-regulated pathways,but the pathophysiological process of MAC is much more complex and unclear,and there has been a preliminary exploration of the relationship between Lp(α)and MAC.To make the current relationship between the two clearer,and thus provide new possibilities for preventing or delaying MAC,the paper will review the three aspects of MAC,Lp(α),and the research progress between the two.

This study was aimed at exploring the epidemiological characteristics of plague,and the evolutionary relation-ships among the isolated plague strains in the Yunnan border area,to provide clues for further studying epidemic causes and ep-idemiological patterns.Plague epidemic data in the border area during the second epidemic period(1982-2007)were collected and analyzed with descriptive epidemiological methods.Whole genome sequences of 262 strains of Yersinia pestis in the border area were obtained for phylogenetic analysis.Plague outbreaks occurred in 17 counties(cities)among 25 border counties(cit-ies);a total of 552 epidemic foci and 123 human cases were identified.The 1.ORI2,1.ORI3,1.IN3,2.ANT and 2.MED geno-types were identified among Yersinia pestis isolated from the Yunnan border area,among which the 1.ORI2 population was dominant.A total of 258 strains of Yersinia pestis from the 1.OR12 population belonged to four subclusters.The Myanmar and Vietnam clade was embedded within the Yunnan clade in the overall phylogeny.The above results indicated that during the sec-ond period of the epidemic,the intensity of plague epidemics in Yunnan's border areas was high,showing a trend of devel-opment from west to south and east.Our findings indicated a risk of cross-border transmission of plague between Yunnan and neighboring countries;therefore,the surveillance,pre-vention,and control of plague in border areas should be strengthened.

This study was aimed at creating an engineered strain of Bacillus subtilis for efficient expression of biologically active type 2 toxin B(TcdB2)derived from a highly virulent strain of Clostridium difficile.The TcdB2 gene was cloned from ST1/RT027 strain genome DNA,incorporated into the PHT01 vector,and then transformed into B.subtilis strain WB800N for prokaryotic expression.Cell toxicity assays revealed that the recombinant TcdB2 exhibited cytotoxic effects in various cells.The engineered B.subtilis strain effectively expressed biologically active TcdB2,thus providing a basis for further exploration of the pathogenic mechanisms of highly virulent strains of C.difficile and establishing a foundation for potential vaccine can-didate targets.

The implementation of amplicon sequencing and metagenomic sequencing methods in the whole-genome sequen-cing for MPXV testing was compared,to provide a technical reference for sequencing,tracing,and epidemic prevention and control of MPXV.For amplicon sequencing,targeted amplification of the viral whole genome was performed on MPXV DNA,and was followed by next-generation sequencing of the amplification products.For metagenomic sequencing,next-generation sequencing was performed directly on MPXV DNA.After the sequences were obtained,software such as CLC and IGV were used to analyze the effective data percentage,sequencing depth,and whole-genome sequencing coverage under different sequen-cing depths for both sequencing methods,to evaluate sequencing quality.Nextclade was used to analyze virus typing,muta-tions,and deletions.Subsequently,the similarity and completeness of sequences obtained through both sequencing methods were further compared.On the basis of mapping to the refer-ence sequence of strain MPXV-M5312_HM12_Rivers(Gen-Bank number NC_063383.1),the percentage effective data obtained from amplicon sequencing and metagenomic sequen-cing was 99.72％and 7.54％,respectively,with a sequencing depth range of 0× to 334 839 ×,and 44 × to 1 000 ×.On the basis of a sequencing depth of 10 ×,the site coverage of the above was 90.3％and 100％,respectively.IGV was used to validate the whole-genome coverage under different sequencing depths.The depth coverage of whole-genome sites for metagenomic sequencing was uniform,whereas that of the whole-genome sites for amplicon sequencing was uneven and significantly differed.Virus typing and sequence similarity analysis indicated that the viral sequences obtained with the two sequencing methods all belonged to the Ⅱb B.1 lineage of MPXV.Comparison with the reference sequence indicated that metagenomic sequencing identified 73 nucleotide mutation sites,whereas amplicon sequen-cing identified 68 mutation sites.Further analysis demonstrated that seven common mutation sites of Ⅱb B.1 were not detected in the amplicon sequencing,and two false positive private mutation sites were identified.Amplicon or metagenomic sequencing methods thus can be flexibly used in MPXV virus whole-genome sequencing.Amplicon sequencing yields more effective data,whereas metagenomic sequencing provides better uniformity of coverage and sequence accuracy.This study provides a prelimi-nary understanding of the efficacy of each method and may serve as a technical reference for improving the success rate of whole-genome sequencing of MPXV.

Objective:To detect the pharmacokinetic(PK)parameters of coagulation factor Ⅷ(FⅧ)in adult patients with severe hemophilia A,identify the potential factors influencing FⅧ PK,and optimize the use of FⅧ in individual prophylaxis regimens.Methods:PK characteristics of FⅧ were studied in a total of 23 severe hemophilia A adults.The correlation of patients'characteristics including age,von Willebrand factor antigen(vWF:Ag),blood group,weight,body mass index(BMI)and FⅧ genotype,with FⅧ PK were evaluated.Individual prophylaxis regimens were given based on FⅧ PK parameters.Results:The mean terminal half-life(t1/2)of FⅧ was 20.6±9.3 h,ranged from 11.47 h to 30.12 h.The age(r=0.580)and vWF:Ag(r=0.814)were significantly positively correlated with t1/2 of FⅧ.The mean area under the plasma concentration curve(AUC)of FⅧ was 913±399(328-1 878)IU h/dl,and the AUC of FⅧ was positively correlated with age(r=0.557)and vWF:Ag(r=0.784).The mean residence time(MRT)of FⅧ was 24.7±12.4(13.2-62.2)h,and the MRT of FⅧ was positively correlated with age(r=0.664)and vWF:Ag(r=0.868).The mean in vivo recovery(IVR)of FⅧ was 2.59±0.888(1.5-4.29)IU/dl per IU/kg,the mean clearance(CL)of FⅧ was 3±1.58(0.97-7.18)ml/(kg·h),and there was no significant correlation of IVR and CL with age and vWF:Ag.According to the individual PK parameters,ultra low-dose,low-dose and moderate-dose FⅧ were applied to 15,6,2 adults patients with severe hemophilia A for prophylaxis,respectively.Conclusion:There are significant individual differences in the FⅧ half-life of adult patients with severe hemophilia A.The older the patient,the higher the vWF:Ag level,and the longer the FⅧ half-life.Individual administration is required based on the FⅧ PK parameters to optimize prophylaxis treatment.

Objective:To clarify the causal relationship between obesity and male infertility through Mendelian randomization(MR)study.Methods:We assessed the causal effect of genetically predicted body mass index(BMI)on the risk of male infertility via a two-sample MR analysis,with the BMIs of 99 998 cases and 12 746 controls as the exposure factor and genetic information on male infertility obtained from a genome-wide association study of 73 479 Europeans.In the univariable MR(UVMR)analysis of the causal relationship,we mainly used inverse variance weighting(IVW),with MR-Egger regression and weighted median filtering as the supplementary methods.Sensitivity analyses including the Cochran's Q test,Egger intercept test,MR-PRESSO,leave-one-out analysis and funnel plot were performed to verify the robustness of the MR results.To evaluate the direct causal effects of BMI on MI risk,mult-ivariable MR(MVMR)was performed.Results:UVMR indicated a causal relationship between genetically predicted BMI and an in-creased risk of male infertility(OR:1.237,95%CI:1.090-1.404,P=0.001).Sensitivity analysis revealed little evidence of bias in the current study(P>0.05).With such risk factors as type 2 diabetes,alcohol consumption and smoking adjusted,MVMR confirmed a direct causal effect of genetically predicted BMI on the risk of male infertility(P<0.05).Conclusion:Genetically pre-dicted BMI may be associated with an increased risk of male infertility.Further studies are expected to explore the underlying mecha-nisms of this association and provide some new strategies for the prevention and treatment of BMI-related male infertility.