Objective The aim is to utilize CRISPR/Cas9 gene editing technology to construct Dmd gene mutant mice with a point mutation in exon 23 of the Dmd gene. Subsequently, the phenotypic changes of the mice in muscles and immune systems are analyzed and verified, providing an evaluation model for Duchenne muscular dystrophy and other related diseases.MethodsBased on the sequence characteristics of exon 23 of the Dmd gene, small guide RNA (sgRNA) was designed and synthesized. Cas9 mRNA, sgRNA fragments, and oligo donor DNA were microinjected into fertilized eggs of C57BL/6J mice. After transferring the fertilized eggs to surrogate mice, F0 generation mice were born. After mating with F0 generation mice, offspring mice were obtained, and Dmd gene positive mutant (Dmd^Mu/+) mice were obtained after genotype identification. Male hemizygous Dmd^Mu/+(Dmd^Mu/Y) mice were selected for phenotype validation. The body weight of live 3- and 9-month-old mice were recorded. Muscle tension was evaluated through the grid test. Hearts and semitendinosus muscles were collected, and the histopathological changes were observed using HE staining. Further, the expression of Dmd protein in muscle tissue of 9-month-old mice was analyzed by Western blotting.An acute inflammation model was established in Dmd^Mu/Y mice using lipopolysaccharide induction. Peripheral blood from the submandibular vein was collected, and the changes in the proportion of neutrophils and monocytes were detected by flow cytometry.Results The results of genome sequencing and Western blotting confirmed the successful construction of Dmd gene point mutant mice (Dmd^Mu/+ mice). Dmd protein expression was not detected in skeletal muscle and myocardium of Dmd^Mu/+ mice, and it was significantly reduced compared to wild-type C57BL/6J mice (P<0.05). Compared with wild-type mice of the same background, Dmd^Mu/Y mice at 3 and 9 months of age showed significant weight loss (P<0.01) and decreased muscle tension (P<0.05). 9-month-old Dmd^Mu/Y mice exhibited significant pathological changes in skeletal muscle and myocardium, including widening of intermuscular space. Under normal condition, compared with wild-type mice, the proportion of neutrophils and monocytes in the peripheral blood of 3-month-old Dmd^Mu/Y mice was significantly lower than that of wild-type mice (P<0.01). After lipopolysaccharide stimulation, the proportion of neutrophils in peripheral blood of 3-month-old Dmd^Mu/Y mice remained significantly lower compared to that of wild-type mice (P<0.01). The proportion of neutrophils in peripheral blood of 9-month-old Dmd^Mu/Y mice significantly decreased after lipopolysaccharide induction (P<0.01), with a trend of change observed in monocytes between groups.Conclusion The successful construction of the Dmd gene mutant mouse model has confirmed the vital function of Dmd gene in maintaining normal muscle tissue morphology and muscle tone. It preliminarily indicated that Dmd gene deletion could significantly reduce the proportion of neutrophils in peripheral blood, offering a new perspective for the study of immune system alterations in Duchenne muscular dystrophy patients.

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.

Background::Contrast-enhanced ultrasound (CEUS) can detect lesions hidden in inflammatory regions and find necrosis or areas of severe fibrosis within the lesion. This retrospective study aimed to compare the diagnostic accuracy of solid pancreatic lesions using percutaneous ultrasound (US)-guided fine-needle aspiration (FNA) with or without CEUS assessment.Methods::Clinical, imaging, and pathologic data of 181 patients from January 2014 to December 2018 in Pecking Union Medical College Hospital, with solid pancreatic masses who underwent percutaneous US-FNA and ThinPrep cytologic test were retrospectively evaluated. Patients were divided into CEUS and US groups according to whether CEUS was performed before the biopsy. According to FNA cytology diagnoses, we combined non-diagnostic, neoplastic, and negative cases into a negative category. The positive category included malignant, suspicious, and atypical cases. The final diagnosis was confirmed by pathology or clinical and radiological follow-up for at least 12 months. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of US-FNA were evaluated between the two groups.Results::This study enrolled 107 male and 74 female patients (average age: 60 years). There were 58 cases in the US group and 123 cases in the CEUS group. No statistically significant differences in age, gender, or lesion size were found between the two groups. The diagnostic accuracy of the CEUS group was 95.1% (117/123), which was higher than the 86.2% (50/58) observed in the US group ( P = 0.036). The sensitivity, specificity, PPV, and NPV of the CEUS group were increased by 7.5%, 16.7%, 3.4%, and 18.8%, respectively, compared with the US group. However, the differences of the two groups were not statistically significant. Conclusions::Compared with the conventional US, the use of CEUS could improve the biopsy accuracy and avoid the need for a repeat biopsy, especially for some complicated FNA cases.

AL3810, a molecular dual inhibitor of the vascular endothelial growth factor receptor (VEGFR) and fibroblast growth factor receptor (FGFR), has earned the permission of phase II clinical trial for tumor treatment by China FDA. As a reversible ATP-competitive inhibitor, AL3810 targets ATP-binding site on intracellular region of VEGFR and FGFR, whereas, AL3810 lacking interplay with extracellular region of receptors rendered deficient blood-brain tumor barrier (BBTB) recognition, poor brain penetration and unsatisfactory anti-glioma efficacy. Integrin

Objective:To investigate the efficacy and safety of non-penetrating trabecular surgery combined with nearly 360-degree suture trabeculotomy for the treatment of primary congenital glaucoma (PCG).Methods:An observational case series study was conducted.A total of 29 cases (50 eyes) with PCG, including 21 males (35 eyes) and 8 females (15 eyes), were enrolled in Jiangsu Province Hospital and Nanjing Children's Hospital from January to November, 2019.The age of subjects ranged from 1 month to 4 years, and the median age was 6 months.Non-penetrating trabecular surgery was first performed in order to open the Schlemm canal.The cannulation and nearly 360-degree suture trabeculotomy were then performed with the twisted 6-0 polypropylene suture.Intraocular pressure (IOP), corneal diameter, cup-to-disc ratio (c/d) and complications were recorded preoperatively and 1 week, 1 month, 3 months, 6 months, 9 months, 12 months, and 24 months postoperatively, and the proportion of sutures successfully passed through the Schlemm canal and the success rate of operation were recorded.This study followed the Declaration of Helsinki.The study protocol was approved by an Ethics Committee of The First Affiliated Hospital of Nanjing Medical University (No.2019-SR-198). Written informed consent was obtained from the guardian of each subject prior to entering the study cohort.Results:Circumferential cannulation by suture was successfully performed in 90% of the subjects.The Harms trabeculotomy probe was applied in failed cases.Mean IOP was significantly lowered from preoperative (35.0±9.5) mmHg (1 mmHg=0.133 kPa) to (9.9±4.4), (10.0±4.2), (9.7±4.4), (9.0±2.9), (9.4±4.2), (9.3±3.3) and (9.5±3.8) mmHg at postoperative 1 week, 1 month, 3 months, 6 months, 9 months, 12 months and 24 months, respectively ( F=141.56, P<0.01). Mean corneal diameter was significantly reduced from preoperative (13.7±1.4) mm to (13.3±1.4), (12.9±1.4), (12.8±1.3), (12.7±1.2), (12.6±1.1), (12.6±1.1) and (12.8±0.4) mm at postoperative 1 week, 1 month, 3 months, 6 months, 9 months, 12 months and 24 months, respectively ( F=4.55, P<0.01). Mean c/d was significantly reduced from preoperative 0.81±0.15 to 0.55±0.22, 0.48±0.23, 0.45±0.22, 0.43±0.21, 0.41±0.20, 0.40±0.21 and 0.31±0.19 at postoperative 1 week, 1 month, 3 months, 6 months, 9 months, 12 months and 24 months, respectively ( F=21.07, P<0.01). Forty-two eyes (93.3%) achieved complete success and 45 eyes (100%) achieved qualified success at postoperative 12 months.No severe complications were observed during or after surgery. Conclusions:Non-penetrating trabecular surgery combined with nearly 360-degree suture trabeculotomy can effectively treat patients with PCG without any severe complications.

Objective To observe the effect of Kinesio Taping with lattice shapes on pregnancy-related low back pain (PLBP). Methods From March, 2017 to April, 2018, 56 patients with PLBP were randomly divided into the control group (n = 28) and experimental group (n = 28). Both groups received the core stability training, while the experimental group accepted Kinesio Taping with lattice shapes additionally. They were assessed with Visual Analogue Scale (VAS), Roland-Morris Dysfunction Questionnaire (RMDQ), range of lumbar activity and torso angle before, three days and two weeks after treatment. Results The range of lumbar activity improved significantly in both groups (t > 6.327, P < 0.01) three days after treatment, while the scores of VAS and RMDQ, and the torso angle improved significantly in the experimental group (t > 4.862, P < 0.001). The scores of VAS and RMDQ, the range of lumbar activity, and the torso angle improved significantly in both groups two weeks after treatment (P < 0.001), and improved more in the experimental group than in the control group (P < 0.05). Conclusion Kinesio Taping with lattice shapes combined with core stability training can further reduce the lower back pain and improve the function for the PLBP patients.

Objective · To investigate the status of depression and anxiety in patients with recurrent spontaneous abortion (RSA) and the possible influence factors and to provide theoretical support for further psychological intervention. Methods · RSA patients and women with no history of RSA were invited to complete a questionnaire, including basic information, Self-Rating Depression Scale (SDS) and Self-Rating Anxiety Scale (SAS). All data were analyzed by SPSS. Results · Of all 1064 cases included in this study, 725 were RSA cases, 217 cases with one spontaneous abortion and 122 in control group with no history of spontaneous abortion. Our results showed that both RSA patients and patients with one spontaneous abortion have significantly higher SDS and SAS scores than control group. Furthermore, non-pregnant RSA patients with lower education level, lower household income and 3-5 years of marriage have significantly higher levels of depression and anxiety. Patients with multiple miscarriages (≥4), history of induced abortion and no live birth, score significantly higher in SDS. Conclusion · Whether pregnant or not, RSA patients are much easier to become depressive and anxious, which may be associated with education level, household income, length of marriage, numbers of pregnancy losses and previous live birth. Women with one spontaneous abortion also show a significant higher tendency of depression and anxiety. These patients should be given proper psychological intervention if necessary.

Objective To analyze the mammographic features of invasive lobular carcinoma (ILC)compared to those of invasive ductal carcinoma (IDC).Methods Twenty cases with ILC and 95 cases with IDC were retrospectively evaluated by two breast radi-ologists according to the Breast Imaging Reporting and Data System (BI-RADS)lexicon.The mammographic findings were com-pared between ILC and IDC with the independent samples chi-square test or Fisher’s exact test,as appropriate.Results Mass was the most common finding in both ILCs and IDCs,but less frequent in ILCs (36.4% vs 63.9%,P =0.008).Mass in ILCs was more frequently lobular or irregular shape with spiculated margin.Architectural distortion and focal asymmetry were more frequent in ILCs than in IDCs,however,the differences were no significant.The frequency of calcifications was not significantly different between the two groups.The distributions of calcifications were more regional in ILCs,and more segmental or linear in IDCs (P =0.01).Conclu-sion ILCs are more usually shown as non-mass appearances on mammography.ILCs that appeared as mass are more frequently ir-regular in shape with spiculated margins.

Objective To establish normal reference interval for four items of blood coagulation on ACL‐TOP Automatic coagu‐lation analyzer .Methods The fasting anti‐coagulation blood samples were collected from 1 268 inpatients and people conducted physical examination ,all subjects without liver disease ,history of blood disease and coagulation disfunction .The prothrombin time (PT) ,activated partical prothrombin time(APTT) ,thrombin time(TT) and serum levels of fibrinogen(FIB) were determined by u‐sing ACL‐TOP automatic coagulation analyzer which was producted by America IL company .And data of determination results were used to establish the normal reference intervals of indexes in this laboratory .Results The precision and accuracy of this analy‐zer was good .There were differences of normal reference intervals between which established in this laboratory and which provided by the manufacturer .Conclusion Each laboratory should establish its own normal reference interval ,not blindly refer to reference interval provided by regents manual .

Objective To investigate the self-transcendence of the elderly patients with type 2 diabetes,and analyze the influencing factors. Methods A convenient sample design was used and a random questionnaire survey was conducted among 211 community elderly patients with type 2 diabetes for the current situation and influencing factors of self-transcendence in Taiyuan, from August to October 2014. Results The total score of self-transcendence was (41. 03 ± 4. 64). The surveys showed that the influencing factors of elderly patients′self-transcendence level were marital status, education level, occupation before retirement, monthly income, living conditions, personality characteristics, participation in collective activities, a significant event in half year or not, diabetes process, combined chronic diseases conditions, situation of diabetes complications and health. Further Multiple linear stepwise regression analysis showed that education level, living conditions, participation in collective activities, monthly income, diabetes duration were the main influencing factors ( R=0. 529,R2 =0. 280,F=13. 191;P<0. 01). Conclusions Through the concern of the self-transcendence of the elderly patients with type 2 diabetes, it provides the theoretical basis for future intervention measures, and finally makes the elderly patients with types 2 diabetes who dare to face the negative events in their lives, adjust the state of life, set up the positive outlook on life, continuously surpass ourselves to mature, so as to finally achieves groups of healthy aging and active aging.