Objective To explore the drug selection, usage, dosage and effect of clinical pharmacists in the treatment of secondary Candida bloodstream infection in patients with digestive tract perforation, and provide reference for rational clinical use of such anti-infection therapy. Methods During the treatment of Candida infection, anti-infection specialist clinical pharmacists suggested replacing fluconazole for anti-infection treatment, and adjusted the usage and dosage of caspofungin to ensure the application of full treatment course. Results The patient’s Candida bloodstream infection was effectively controlled. Conclusion Echininocandins such as caspofungin are the first choice for Candida infection. The maintenance dose should be reduced to 35 mg qd in patient with moderate liver function injury, and the anti-infection treatment should be done at least 14 days after the blood culture being negative. Clinical pharmacists participate in clinical pharmaceutical care practices such as clinical ward rounds, and actively assist doctors to develop individualized anti-infection programs, which could improve the level of clinical drug use and the clinical outcome of diseases.

Objective To explore the impact of suture configuration and fixation type on the biome-chanical strength of rotator cuff repair,using a factorial design study.Methods Sixteen fresh-frozen porcine shoulder samples were randomized into an anchorless double-row suture bridge transosseous su-tures(DS)group,an anchored double-row suture bridge transosseous-equivalent(DE)group,an an-chorless X-BOX construct transosseous sutures(XS)group,and an anchored X-BOX construct transos-seous-equivalent(XE)group,each of four,according to suture configuration(double-row suture bridge,traditional X-BOX construct)and fixation type(suture anchors,transosseous sutures).Then,their fatigue resistance(first-cycle excursion,gap length difference ratio,and the percentage of ex-posed footprints)and the failure strength(the maximum failure load and the re-tear type)were mea-sured using a biomechanical material testing machine.Results Different suture configurations affected failure strength(F=39.559,P<0.001),with the double-row suture bridge groups(693.07±58.35 N,746.76±138.57 N)showing significantly higher failure strength,compared to the traditional X-BOX groups(462.90±18.91 N,421.43±90.76 N).However,the fixation type did not significantly im-pact failure strength(F=1.161,P=0.302).Moreover,the suture configuration influenced the gap differ-ence ratio(F=7.781,P=0.016),but had no significant correlation with other fatigue resistance indica-tors(P>0.05).Meanwhile,failure strength and fatigue resistance were not correlated with fixation type,and the interaction between suture and fixation type(P>0.05).The incidence of failure types for the four suture configurations was as follows:Type I tendon tear:XS>XE>DS=DE;type II tendon tear:DS>XE>XS=DE;fixing material-related failure:DE>DS=XE=XS.Conclusion The failure strength and gap formation ratio in rotator cuff repair under fatigue loading are influenced by suture configuration,whereas no significant association has been observed with respect to fixation method,whether using transosseous sutures or suture anchors.

Objective To explore the impact of suture configuration and fixation type on the biome-chanical strength of rotator cuff repair,using a factorial design study.Methods Sixteen fresh-frozen porcine shoulder samples were randomized into an anchorless double-row suture bridge transosseous su-tures(DS)group,an anchored double-row suture bridge transosseous-equivalent(DE)group,an an-chorless X-BOX construct transosseous sutures(XS)group,and an anchored X-BOX construct transos-seous-equivalent(XE)group,each of four,according to suture configuration(double-row suture bridge,traditional X-BOX construct)and fixation type(suture anchors,transosseous sutures).Then,their fatigue resistance(first-cycle excursion,gap length difference ratio,and the percentage of ex-posed footprints)and the failure strength(the maximum failure load and the re-tear type)were mea-sured using a biomechanical material testing machine.Results Different suture configurations affected failure strength(F=39.559,P<0.001),with the double-row suture bridge groups(693.07±58.35 N,746.76±138.57 N)showing significantly higher failure strength,compared to the traditional X-BOX groups(462.90±18.91 N,421.43±90.76 N).However,the fixation type did not significantly im-pact failure strength(F=1.161,P=0.302).Moreover,the suture configuration influenced the gap differ-ence ratio(F=7.781,P=0.016),but had no significant correlation with other fatigue resistance indica-tors(P>0.05).Meanwhile,failure strength and fatigue resistance were not correlated with fixation type,and the interaction between suture and fixation type(P>0.05).The incidence of failure types for the four suture configurations was as follows:Type I tendon tear:XS>XE>DS=DE;type II tendon tear:DS>XE>XS=DE;fixing material-related failure:DE>DS=XE=XS.Conclusion The failure strength and gap formation ratio in rotator cuff repair under fatigue loading are influenced by suture configuration,whereas no significant association has been observed with respect to fixation method,whether using transosseous sutures or suture anchors.

Objectives:There is a lack of long-term follow-up study results on severe microvascular complications in a larger Chinese population with diabetes.This study aims to explore long-term impact of newly diagnosed diabetes(NDD)on the incidence and risk of severe microvascular complications.Methods:A total of 598 NDD and 493 normal glucose tolerance(NGT)subjects were included in this study in 1986.By questionnaire and systematic case review,the occurrence of severe microvascular complications,including severe diabetic retinopathy,severe diabetic nephropathy,and severe diabetic neuropathy,was followed up and collected over a period of 34 years.Results:The cumulative incidence of severe microvascular complications in the NDD population was 65.03%(95%CI:58.90%-70.48%)over 34 years,significantly higher than that in the NGT population(16.8%,95%CI:12.64%-20.11%).After adjusting for related risk factors,the risk of severe microvascular complications in the NDD population was 7.08 times than that of the NGT population(HR=7.08,95%CI:5.09-9.84,P<0.0001).Stratified analysis by sex showed that the cumulative incidence and risk of severe microvascular complications were slightly higher in male NDD population(68.02%,95%CI:57.27%-76.61%;HR=9.45,95%CI:5.78-15.47,P<0.0001)than in female NDD population(63.37%,95%CI:55.69%-70.09%;HR=5.86,95%CI:3.75-9.16,P<0.0001);however,the cumulative incidence increased more rapidly in women during the follow-up period of 10-25 years.Conclusions:The incidence and risk of severe microvascular complications in diabetes were significantly higher than those in the NGT population;and the incidence of severe vascular complications increased rapidly after the duration of diabetes exceeded 10 years,indicating that strict control of blood glucose in the early stage of diabetes is of vital importance.

Objectives:There is a lack of long-term follow-up study results on severe microvascular complications in a larger Chinese population with diabetes.This study aims to explore long-term impact of newly diagnosed diabetes(NDD)on the incidence and risk of severe microvascular complications.Methods:A total of 598 NDD and 493 normal glucose tolerance(NGT)subjects were included in this study in 1986.By questionnaire and systematic case review,the occurrence of severe microvascular complications,including severe diabetic retinopathy,severe diabetic nephropathy,and severe diabetic neuropathy,was followed up and collected over a period of 34 years.Results:The cumulative incidence of severe microvascular complications in the NDD population was 65.03%(95%CI:58.90%-70.48%)over 34 years,significantly higher than that in the NGT population(16.8%,95%CI:12.64%-20.11%).After adjusting for related risk factors,the risk of severe microvascular complications in the NDD population was 7.08 times than that of the NGT population(HR=7.08,95%CI:5.09-9.84,P<0.0001).Stratified analysis by sex showed that the cumulative incidence and risk of severe microvascular complications were slightly higher in male NDD population(68.02%,95%CI:57.27%-76.61%;HR=9.45,95%CI:5.78-15.47,P<0.0001)than in female NDD population(63.37%,95%CI:55.69%-70.09%;HR=5.86,95%CI:3.75-9.16,P<0.0001);however,the cumulative incidence increased more rapidly in women during the follow-up period of 10-25 years.Conclusions:The incidence and risk of severe microvascular complications in diabetes were significantly higher than those in the NGT population;and the incidence of severe vascular complications increased rapidly after the duration of diabetes exceeded 10 years,indicating that strict control of blood glucose in the early stage of diabetes is of vital importance.

In order to achieve the purpose of rapid detection of duck astrovirus type 1(DAstV-1),specific primers were designed based on the conservative region of ORF1a which belonged to DAstV-1(WF1202 strain).A real-time fluorescent quantitative PCR(qPCR)detective method for DAstV-1 was established.Clinical samples were detected by the qPCR method and the positive samples were used for virus isolation and identification.Results showed that the detection limit of the established method was 4.64×103 copies/μL,which was 10 times higher than the normal RT-PCR method.In addition,no cross-reactions were found with other common infectious disease pathogens in poultry,indicating that the qPCR method had good specificity.What's more,the coef-ficient of variations(Cv)in intra-and inter-assays were 0.85％-2.85％and 0.21％-2.94％,re-spectively,both less than 3％,indicating that the qPCR method had a good repeatability.Using this method,35 tissue samples from different duck farms in 10 provinces from 2020 to 2022 were detected for DAstV-1.Results showed that the positive rate was 25.71％(9/35),and the coinci-dence rate was 94.29％when compared with the normal RT-PCR method.A positive sample ran-domly taken for the virus isolation through duck embryo passage,and the allantoic fluid was col-lected and then was verified by the qPCR method and inoculated with 1-day-old healthy ducklings for the animal regression experiment.The infected ducklings suffered from transient disease but did not die.The liver tissues were all positive with DAstV-1 when detected by qPCR.Meanwhile,autopsy showed that there were slight changes in the livers,and the histopathological observation showed that the liver cells were steatosis.These findings indicated that the isolated DAstV-1 strain had weak pathogenicity and might be a low virulent strain.To sum up,the qPCR detection method of DAstV-1 was successfully established in this work,and could provide technical support for clini-cal diagnosis,isolation and identification,and molecular epidemiology monitoring of DAstV-1.

Objective To investigate the predictive value of a decision tree-based machine learning model for prognosis in acute paraquat(PQ)poisoning(APP)patients.Methods A retrospective study was conducted.The clinical data of APP patients from Cangzhou Central Hospital between May 2012 and August 2021 were collected,including gender,age,time from ingestion to gastric lavage,proportion of hemoperfusion,serum PQ concentration,biochemical indicators[white blood cell count(WBC),alanine aminotransferase(ALT),serum creatinine(SCr),serum amylase,and serum potassium],and blood gas indicators[arterial blood lactic acid(Lac),base excess(BE),and arterial partial pressure of oxygen(PaO2)].Patients were divided into a survival group(n = 56)and a death group(n = 74)based on 90-day prognosis,and the clinical data between the two groups were compared.The multivariate Logistic regression analysis was conducted to analyze the risk factors of prognosis in APP patients,and two decision tree models(i.e.,with/without serum PQ concentration)were constructed based on the risk factors.The predictive value was evaluated by the receiver operator characteristic(ROC)curve,and the area under the ROC curve(AUC)of two decision tree models was compared by Hanley&McNeil method.Results The 90-day survival rate of the patients was 43.1%(56/130).Compared with death group,patients in the survival group had lower WBC[×109/L:8.9(7.0,11.6)vs.17.4(11.9,23.1)],ALT[U/L:25.3(21.2,31.8)vs.29.3(23.2,40.3)],SCr[μmol/L:64.0(53.0,74.0)vs.91.0(72.5,141.5)],Lac[mmol/L:2.5(1.4,4.0)vs.7.1(3.7,11.0)],and serum PQ concentration[ng/L:0.3(0.1,0.9)vs.2.9(1.9,8.1)],the difference were statistically significant(all P<0.05),higher BE[mmol/L:-2.5(-4.2,-1.1)vs.-7.2(-10.9,-4.7)]and serum potassium[mmol/L:3.7(3.5,4.0)vs.3.2(2.8,3.7)],the difference were statistically significant(all P<0.05),and patients were younger[years:33.5(26.0,47.8)vs.42.5(26.0,58.0),P<0.05].Univariate Logistic regression analysis showed that age,WBC,ALT,SCr,serum potassium,Lac,BE and serum PQ concentration were independent risk factors of 90-day survival[odds ratio(OR)and 95%confidence interval(95%CI)were 1.03(1.01-1.05),1.30(1.18-1.44),1.04(1.01-1.07),1.02(1.01-1.04),7.59(3.25-17.70),1.64(1.35-1.99),1.51(1.29-1.76),7.00(3.41-14.37),P values were 0.018,<0.001,0.011,<0.001,<0.001,<0.001,<0.001,<0.001].Multivariate Logistic regression analysis with serum PQ concentration showed that WBC,serum potassium,and serum PQ concentration were independent risk factors for 90-day survival[OR and 95%CI were 1.17(1.03-1.33),7.29(1.66-32.01),5.49(2.48-12.13),P values were 0.014,0.008,<0.001].Multivariate Logistic regression analysis without serum PQ concentration showed that age,WBC,serum potassium and BE were independent risk factors for 90-day survival[OR and 95%CI were 1.05(1.01-1.08),1.20(1.07-1.34),3.12(1.01-9.66),1.41(1.16-1.72),P values were 0.008,0.002,0.049,0.001].The decision tree model based on serum PQ concentration and serum potassium showed an AUC of 0.94(95%CI was 0.89-0.98),along with 91.9%sensitivity,89.3%specificity,and 90.0%accuracy.The decision tree model based on WBC,BE,and age showed an AUC of 0.89(95%CI was 0.84-0.95),with 86.5%sensitivity,91.1%specificity,and 88.5%accuracy.Pairwise comparison of the AUC using Hanley&McNeil method demonstrated that no statistical difference between the two decision tree models(Z = 1.34,P = 0.180).Conclusion The decision tree-based models can provide quantitative and intuitive prediction tools for the early detection of prognosis in APP patients in clinical practice.

In order to achieve rapid detection of duck hepatitis A virus type 3(DHAV-3),this ex-periment initially performed prokaryotic expression of the non-structural protein 3D of DHAV-3,followed by immunization of BALB/c mice with the purified protein.After immunization,mouse spleen cells were fused with myeloma cells(SP2/0)to prepare monoclonal antibodies.Subsequent-ly,a double-antibody sandwich ELISA(DAS-ELISA)detection method was established using the monoclonal antibodies,and its sensitivity,specificity,and repeatability were evaluated.Finally,the established method was applied to the detection of clinical samples and validated for compliance with the RT-PCR method.The results showed that the DHAV-3 3D protein was efficiently ex-pressed in BL21(DE3),and its specificity was confirmed by Western blot after purification.After cell fusion and three rounds of subcloning,six hybridoma cells were successfully screened and named 1A3,1B6,1C7,1D9,2A1,and 3A9.The subtype identification of the antibodies showed that 1A3 belonged to IgG2b,1B6 belonged to IgG2a,3A9 belonged to IgG3,and 1C7,1D9,and 2A1 be-longed to IgG1.After screening,the high-affinity monoclonal antibodies 1B6 and 1 A3 were selected as the capture antibody and detection antibody,respectively,and use to establish the DAS-ELISA detection method.After optimizing the reaction conditions,the optimal coating concentration of the capture antibody 1B6 was determined to be 1×10-3 g/L,and the optimal dilution of the detection antibody 1A3 was 1∶1 000.The cut-off value was established as 0.256.The sensitivity test showed that the method had a minimum detection limit of 4.0 ×10-4 g/L for the 3D protein.The repeat-ability test showed that the within-batch and between-batch coefficients of variation were both less than 9％,indicating good repeatability.The specificity test showed that the method did not show specific reactions with duck adenovirus(DAdV),muscovy duck parvovirus(MDPV),duck circo-virus(DuCV),duck plague virus(DPV),duck reovirus(DRV),or Riemerella anatipestifer(RA),but cross-reacted with Duck hepatitis a virus type 1(DHAV-1),allowing simultaneous de-tection of DHAV-3 and DHAV-1 pathogens.The DAS-ELISA method established in this experi-ment was compared with the RT-PCR method for the detection of 186 clinical samples,and the DAS-ELISA method could simultaneously identify DHAV-1 and DHAV-3,with a compliance rate of 98.9％compared to the RT-PCR method.In conclusion,the established DAS-ELISA method showed good repeatability and high sensitivity,and can be used for the diagnosis of DHAV-1 and DHAV-3,providing technical support for the epidemiological investigation and prevention of Duck Hepatitis A.

In order to achieve rapid detection of duck hepatitis A virus type 3(DHAV-3),this ex-periment initially performed prokaryotic expression of the non-structural protein 3D of DHAV-3,followed by immunization of BALB/c mice with the purified protein.After immunization,mouse spleen cells were fused with myeloma cells(SP2/0)to prepare monoclonal antibodies.Subsequent-ly,a double-antibody sandwich ELISA(DAS-ELISA)detection method was established using the monoclonal antibodies,and its sensitivity,specificity,and repeatability were evaluated.Finally,the established method was applied to the detection of clinical samples and validated for compliance with the RT-PCR method.The results showed that the DHAV-3 3D protein was efficiently ex-pressed in BL21(DE3),and its specificity was confirmed by Western blot after purification.After cell fusion and three rounds of subcloning,six hybridoma cells were successfully screened and named 1A3,1B6,1C7,1D9,2A1,and 3A9.The subtype identification of the antibodies showed that 1A3 belonged to IgG2b,1B6 belonged to IgG2a,3A9 belonged to IgG3,and 1C7,1D9,and 2A1 be-longed to IgG1.After screening,the high-affinity monoclonal antibodies 1B6 and 1 A3 were selected as the capture antibody and detection antibody,respectively,and use to establish the DAS-ELISA detection method.After optimizing the reaction conditions,the optimal coating concentration of the capture antibody 1B6 was determined to be 1×10-3 g/L,and the optimal dilution of the detection antibody 1A3 was 1∶1 000.The cut-off value was established as 0.256.The sensitivity test showed that the method had a minimum detection limit of 4.0 ×10-4 g/L for the 3D protein.The repeat-ability test showed that the within-batch and between-batch coefficients of variation were both less than 9％,indicating good repeatability.The specificity test showed that the method did not show specific reactions with duck adenovirus(DAdV),muscovy duck parvovirus(MDPV),duck circo-virus(DuCV),duck plague virus(DPV),duck reovirus(DRV),or Riemerella anatipestifer(RA),but cross-reacted with Duck hepatitis a virus type 1(DHAV-1),allowing simultaneous de-tection of DHAV-3 and DHAV-1 pathogens.The DAS-ELISA method established in this experi-ment was compared with the RT-PCR method for the detection of 186 clinical samples,and the DAS-ELISA method could simultaneously identify DHAV-1 and DHAV-3,with a compliance rate of 98.9％compared to the RT-PCR method.In conclusion,the established DAS-ELISA method showed good repeatability and high sensitivity,and can be used for the diagnosis of DHAV-1 and DHAV-3,providing technical support for the epidemiological investigation and prevention of Duck Hepatitis A.

Objective To explore the effect of mucle force on contact force, peak pressure and contact area of foot joint in in vitro biomechanical experiment of foot and ankle, so as to provide references for choosing appropriate loading modes. Methods In neutral position of the ankle joint, fresh calf and foot specimens were simulated with or without mucle force loading. The contact force, peak pressure and contact area of the 1st metatarsophalangeal joint, the 2nd metatarsophalangeal joint, the 1st tarsometatarsal joint, the 2nd tarsometatarsal joint, the medial cuneonavicular joint, the intermediate cuneonavicular joint, the talonavicular joint, the calcicocuboid joint, the subtalar joint ( posterior articular surface) and the tibiotalar joint of normal foot under loading were measured, the results are compared and analyzed. Results Under muscle force loading, the contact force of the 1st metatarsophalangeal joint, the 2nd metatarsophalangeal joint, the 1st tarsometatarsal joint,the 2nd tarsometatarsal joint, the medial cuneonavicular joint, the intermediate cuneonavicular joint, the talonavicular joint and the tibiotalar joint were significantly greater than those without muscle force loading (P<0. 05), and the change percentages were 719. 28% , 311. 37% , 128. 67% , 50. 82% , 54. 89% , 57. 63% ,79. 98% and 50. 34% , respectively. The peak pressures of the 1st metatarsophalangeal joint , the 1st tarsometatarsal joint and the talonavicular joint under muscle force loading were significantly higher than those without muscle force loading ( P < 0. 05), and the change percentages were 176. 14% , 62. 91% and 40. 07% ,respectively. The contact area of the 1st metatarsophalangeal joint, the 1st tarsometatarsal joint, the intermediate cuneonavicular joint and the subtalar joint ( posterior articular surface) under muscle force loading increased significantly (P<0. 05), and the change percentages were 132. 20% , 55. 41% , 30. 97% and 26. 87% , respectively. Conclusions In biomechanical experiment of foot and ankle specimens, muscle force loading has a significant effect on contact force, peak pressure and contact area of each foot joint, especially the forefoot.Therefore, it is necessary to consider the effect of muscle force loading on stress of foot and ankle in the study ofrelated in vitro specimens