Objective To monitor the antifungal resistance of clinical isolates of Candida spp.in the East China region.Methods MALDI-TOF MS or molecular methods were used to re-identify the strains collected from January 2018 to December 2022.Antifungal susceptibility testing was performed using the broth microdilution method.The susceptibility test results were interpreted according to the breakpoints of 2022 Clinical and Laboratory Standards Institute(CLSI)documents M27 M44s-Ed3 and M57s-Ed4.Results A total of 3 026 strains of Candida were collected,65.33％of which were isolated from sterile body sites,mainly from blood(38.86％)and pleural effusion/ascites(10.21％).The predominant species of Candida were Candida albicans(44.51％),followed by Candida parapsilosis complex(19.46％),Candida tropicalis(13.98％),Candida glabrata(10.34％),and other Candida species(0.79％).Candida albicans showed overall high susceptibility rates to the 10 antifungal drugs tested(the lowest rate being 93.62％).Only 2.97％of the strains showed dose-dependent susceptibility(SDD)to fluconazole.Candida parapsilosis complex had a SDD rate of 2.61％and a resistance rate of 9.42％to fluconazole,and susceptibility rates above 90％to other drugs.Candida glabrata had a SDD rate of 92.01％and a resistance rate of 7.99％to fluconazole,resistance rates of 32.27％and 48.24％to posaconazole and voriconazole non-wild-type strains(NWT),respectively,and susceptibility rates above 90％to other drugs.Candida tropicalis had resistance rates of 29.55％and 26.24％to fluconazole and voriconazole,respectively,resistance rates of 76.60％and 21.99％to posaconazole and echinocandins non-wild-type strains(NWT),and a resistance rate of 2.36％to echinocandins.Conclusions The prevalence and species distribution of Candida spp.in the East China region are consistent with previous domestic and international reports.Candida glabrata exhibits certain degree of resistance to fluconazole,while Candida tropicalis demonstrates higher resistance to triazole drugs.Additionally,echinocandins resistance has emerged in Candida albicans,Candida glabrata,Candida tropicalis,and Candida parapsilosis.

To clone and express the K26 gene of Leishmania isolated from three types of visceral leishmaniasis epidemic ar-eas in China and evaluate its effect on detecting specific antibodies against visceral leishmaniasis.The K26 fragments from Leishmania isolated KS-6,SC6 and JIASHI-1 was synthesized and cloned into pET32a vector.The recombinant plasmid pET32a-K26 was transformed into Escherichia coli BL21 strains and induced by isopropyl-β-D-thiogalactopyranoside(IPTG).The expressed recombinant protein was purified by the His-tagged affinity column(Ni-NTA).Serum samples of 110 visceral leishmaniasis patients were used for evaluating the sensitivity by ELISA.Serum samples from patients with malaria,schisto-somiasis japonica,cystechinococcosis,toxoplasmosis,paragon-imiasis,clonorchiosis and 40 healthy people were used for eval-uating the specificity.Detection results of ELISA were compared with that of rK39 strip of American InBios company.Comparation among three K26 antigens were given by x2 test.The sensitivity of the recombinant K26 protein of KS-6,SC6 and JIASHI-5 strains of Leishmania and rK39 strip test to detect the sera of patients with visceral leishmaniasis was 90.00％(99/110),92.73％(102/110),90.91％(100/110)and 93.64％(103/110),respectively.There was no cross reactivity with malaria(10),schistosomiasis japonica(10),cystechinococcosis(10),toxoplasmosis(5),paragonimiasis(5)and clonorchiosis(5),and 40 sera from healthy people were also negative.The specificity was 100.00％.There was no statistical difference in the sensitivity of the recombinant K26 protein of KS-6,SC6 and JIASHI-1 strains of Leishmania and rK39 strip test,x2 values are 0.97,0.07 and 0.57 respectively and the P values are 0.33,0.79 and 0.45,respectively.There was no statis-tical difference in the sensitivity of three K26 antigens(x2=0.53,P=0.97).Conclusion The recombinant K26 antigen has po-tential application value in the diagnosis of visceral leishmaniasis.

Objective To investigate the effect and mechanism of IL-17 on heart failure(HF)in hy-pertensive rats based on NF-κB/sarco-endoplasmic reticulum calcium ATPase 2(SERCA2)signa-ling pathway.Methods Thirty SPF male spontaneously hypertensive rats(SHR)aged 6-8 weeks were divided into control group,model group,phosphate buffer salt(PBS)solution injec-tion group(PBS group),IL-17 protein injection group(IL-17 group)and IL-17 and antibody injec-tion group(IL-17+IgG group),with 6 animals in each group.Hypertensive HF model was estab-lished,and corresponding agents were applied to the PBS group,IL-17 group and IL-17+IgG group intraperitoneally,respectively.The role of IL-17,NF-κB and SERCA2 in hypertensive HF was studied with HE staining,immunohistochemical assay,Western blotting,RT-qPCR and ELISA.Results Significantly higher serum levels of NT-proBNP and IL-17,enhanced myocardial expression of IL-17 mRNA and NF-κB protein,lower serum VEGF level,and down-regulated pro-tein level of SERCA2 in heart tissue were observed in the model group and the PBS group when compared with the control group(P＜0.01).The IL-17 group had obviously higher serum NT-proBNP and IL-17 levels and myocardial expression of IL-17 mRNA and NF-κB protein,and reduced serum VEGF level and SERCA2 protein level in heart tissue than the model group(P＜0.01).IL-17+IgG treatment resulted in notably lower serum IL-17 level and myocardial NF-κB protein level when compared with those of model group(8.98±1.20 vs 11.19±1.22,0.88±0.03 vs 0.93±0.03,P＜0.01),and also resulted in remarkably reduced serum levels of NT-proBNP and IL-17 and myocardial expression of IL-17 mRNA and NF-κB protein but increased serum VEGF level and SERCA2 protein level in heart tissue when compared with the IL-17 group(P＜0.01).The heart rate,SBP,IVSd,LVPWd,LVEDD and LVESD were significantly lower,while LVFS was notably higher in the IL-17+IgG group than the model group and IL-17 group(P＜0.01).The IL-17+IgG group had obviously higher LVEF than the IL-17 group[(70.81±6.50)％vs(62.77±5.43)％,P＜0.01].Conclusion IL-17/NF-κB/SERCA2 signaling pathway is involved in the regulation of inflammatory response after hypertensive HF,and inhibiting IL-17 can effective-ly improve the cardiac dysfunction caused by hypertensive HF.

Objective To design a novel oxygenator to solve the existing problems of extracorporeal membrane oxygenation(ECMO)machine in high transmembrane pressure difference,low efficiency of blood oxygen exchange and susceptibility to thrombosis.Methods The main body of the oxygenator vascular access flow field was gifted with a flat cylindrical shape.The topology of the vascular access was modeled in three dimensions,and the whole flow field was cut into a blood inlet section,an inlet buffer,a heat exchange zone,a blood oxygen exchange zone,an outlet buffer and a blood outlet section.The oxygenator was compared with Quadrox oxygenator by means of ANSYS FLUENT-based simulation and prototype experiments.Results Simulation calculations showed the oxygenator designed was comparable to the clinically used ones in general,and gained advantages in transmembrane pressure difference,blood oxygen exchange and flow uniformity.Experimental results indicated that the oxygenator behaved better than Quadrox oxygenator in transmembrane pressure difference and blood oxygen exchange.Conclusion The oxygenator has advantages in transmem-brane pressure difference,temperature change,blood oxygen ex-change and low probability of thrombosis.[Chinese Medical Equipment Journal,2024,45(3):23-28]

Objective To explore the genetic polymorphism and mutation rate of 36 Y-STR loci in Sichuan Han population and provide basic data for their forensic applications.Methods Blood samples were collected from 307 unrelated male individuals and 367 father-son pairs in Sichuan Han population using FTA blood sampling cards.The Y41SE-v1.2 kit was used to type 36 Y-STR loci,and the population genetic parameters and mutation rates of each locus were calculated.The genetic relationship between Sichuan Han population and other ethnic populations was analyzed in combination with 19 other populations in China.Results A total of 79 mutations were observed in 36 Y-STR loci in 367 father-son pairs of Sichuan Han population,with an average mutation rate of 6.00×10-3.There were 74(93.67%)one-step mutations and 5(6.33%)multi-step mutations.A total of 383 alleles were found at 36 Y-STR loci in 307 Sichuan Han males.The number of alleles at each locus ranged from 5(0.016 29)to 56(0.182 41),GD ranged from 0.100 02(DYS645)to 0.959 99(DYS385),and 306 haplotypes were found.The HD,DC and HMP values were 0.999 973,99.67%and 0.003 284,respectively.The results of genetic distance(Fst)analysis showed that the Sichuan Han population had the closest genetic distance with the Chongqing Han population(0.000 9)and the furthest genetic distance with the Xinjiang Mongolian group(0.032 0).The MDS based on genetic distance was basically consistent with the results of cluster analysis.Conclusion The 36 Y-STR loci have high genetic polymorphism in the Sichuan Han population.The study data can provide data support for the construction of the Y-STR database in this region,and also provide basic genetic information for forensic investigation and population genetics research.

Aggregatibacter aphrophilus(A.aphrophilus)is a normal bacterial flora in the oropharynx,and rarely causes lumbar spine infection in clinical practice.As fastidious bacteria,A.aphrophilus has high nutritional requirements,thus is difficult to be cultured and identified,and prone to be missed in detection.A.aphrophilus was detected from the blood culture of a patient with lumbar spine infection in a hospital.The anti-infection treat-ment based on detection results for the patient was effective after adjusting antimicrobials.This paper reports a rare case of A.aphrophilus lumbar spine infection with literature reviews.

Massive rotator cuff tears, with mean tendon tears>5 cm or involving two or more tendons in a tear, often result in shoulder pain, stiffness, limited range of motion and impaired function, significantly impacting the patients′ quality of life. At present, massive rotator cuff tears are mainly treated surgically with joint cleaning, rotator cuff repair and patch graft repair, etc, but the problems such as tendon end retraction and high rotator tension after surgical repair lead to high postoperative retear rate. The autogenous long head of biceps tendon (LHBT), as an autograft which has the advantages of high accessibility and low cost, has been employed in the repair of massive rotator cuff tears. However, there is still controversy in the choice of specific surgical method. To this end, the authors reviewed the research progress on the application of LHBT in the repair of massive rotator cuff tears, aiming to provide reference for its clinical treatment.

Objective To compare the blood glucose control effect and safety between insulin degludec and insulin aspart and insulin aspart 30 in non-obese patients with type 2 diabetes mellitus(T2DM).Methods Non-obese patients with T2DM were divided into treatment group and control group according to different treatment methods.The control group was treated with insulin aspart 30,and the treatment group was treated with insulin degludec and insulin aspart.Pancreatic islet related indicators[fasting C-peptide(FCP)and 2-hour postprandial C-peptide(2 h CP)],blood glucose control effect[fasting blood glucose(FBG),2-hour postprandial blood glucose(2 h PG)and glycated hemoglobin(HbA1c)],serum 25-hydroxyvitamin D[25(OH)D]and the risk of hypoglycemia were compared between the two groups.Results There were 41 cases in treatment group and 39 cases in control group.After treatment,FCP levels in treatment group and control group were(0.84±0.09)and(1.07±0.14)nmol·L-1;2 h CP levels were(1.03±0.15)and(1.69±0.17)nmol·L-1;FBG levels were(5.46±0.57)and(6.18±0.67)mmol·L-1;2 h PG levels were(8.17±0.85)and(9.03±0.94)mmol·L-1;HbA1 c were(5.35±0.57)％and(6.47±0.68)％;25(OH)D levels were(26.33±2.75)and(20.54±2.17)nmol·L-1,all with significant difference(all P＜0.05).The incidence rates of non-severe hypoglycemia in treatment group and control group were 14.63％and 35.90％,with statistically significant difference(P＜0.05).The incidence rates of severe hypoglycemia in treatment group and control group were 9.76％and 12.82％;the incidence rates of nocturnal hypoglycemia were 19.51％and 17.95％,without statistically significant difference(all P＞0.05).Conclusion The overall therapeutic effect of insulin degludec and insulin aspart on non-obese patients with T2DM is better than that of insulin aspart 30.The former can effectively regulate blood glucose and pancreatic islet cell function,lower the risk of non-severe hypoglycemia.

ObjectiveUltra performance liquid chromatography-quadrupole-electrostatic field orbitrap high resolution mass spectrometry（UPLC-Q-Exactive Orbitrap MS） was used to analyze the differences in chemical components between raw products and wine-processed products of Polygonatum cyrtonema rhizome. MethodUPLC-Q-Exactive Orbitrap MS was used to analyze the chemical compositions of P. cyrtonema rhizome before and after processing， and the effective response ions were extracted after raw data processing， and the differential compounds before and after processing were screened combined with multivariate statistical analysis and according to the conditions of variable importance in the projection（VIP） value>1， P<0.05， fold change（FC）>2 or FC<0.5， based on the retention time， quasi-molecular ions， fragment ions and other information， the components were identified in combination with the control products and the literature， and the significant difference compounds were identified by clustering thermal analysis and relative quantitative analyzed， in order to clarify the change rule of the main components in P. cyrtonema rhizome before and after processing. ResultA total of 72 differential constituents between raw products and wine-processed products were identified， including 15 alkaloids， 12 organic acids， 12 amino acids， 6 flavonoids， 4 saccharides and 23 others. There were a total of 18 significantly different components， among which 13 compounds， including L-malic acid， lactic acid and 9，12，13-trihydroxy-10-octadecenoic acid， showed an increasing trend in content after wine processing， 5 compounds such as trans-3-indoleacrylic acid， L-arginine， D-tryptophan， showed a decreasing trend after processing. ConclusionThe chemical components of P. cyrtonema rhizome are significantly different before and after processing， mainly organic acids， saccharides， amino acids， flavonoids and alkaloids， which can lay the foundation for the in-depth study of the processing mechanism of Polygonati Rhizoma.

Rare diseases still lack effective treatments, and the development of drugs for rare diseases (known as orphan drugs) is an urgent medical problem. As natural active ingredients in living organisms, some biomacromolecule drugs have good biocompatibility, low immunogenicity, and high targeting. They have become one of the most promising fields in drug research and development in the 21st century. However, there are still many obstacles in terms of in vivo delivery. In view of the unique advantages of nanocarriers prepared from polymers, lipids, organic biomimetic and inorganic materials in drug delivery, researchers are committed to building an efficient delivery system with versatility and synergy to solve the bottleneck issues in treating rare diseases with biomacromolecule drugs. Therefore, this article reviews the research progress of nanocarrier delivering proteins, peptides and nucleic acids in the field of rare disease treatment in the past ten years, which provides ideas for researches on biomacromolecule drug nanosystems in the field of treatment of rare diseases.