In this study, we constructed a GLP-2R-HEK293 cell line and established a method for the determination of the in vitro biological activity of teduglutide based on HTRF, after optimizing experimental conditions and methodological verification. We also carried out relative potency detection of teduglutide pharmaceutical products using this method. The result showed that there was a quantitative-efficient relationship between the teduglutide activity and cAMP contents in GLP-2R-HEK293 cells, which conformed to four-parameter model. Method verification results of five concentrations of teduglutide (64%, 80%, 100%, 125% and 156%) met the requirements of the General Rules of Chinese Pharmacopoeia, 2020 edition, Volume IV (9401). We then analyzed the relative potency of three batches of teduglutide drug substances and three batches of drug products. The linearity, regression and parallelism of the obtained curves all fit the system suitability requirements. The relative potency of six batches of teduglutide was from 83% to 105%. In summary, the biological activity detection method established in this study was accurate, precise, simple and time-saving, which can be used for quality control of teduglutide pharmaceutical products.

Background::There is a need for effective and safe therapies for psoriasis that provide sustained benefits. The aim of this study was to assess the efficacy and safety of tildrakizumab, an anti-interleukin-23p19 monoclonal antibody, for treating moderate-to-severe plaque psoriasis in Chinese patients.Methods::In this multi-center, double-blind, phase III trial, patients with moderate-to-severe plaque psoriasis were enrolled and randomly assigned (1:1) to receive subcutaneous tildrakizumab 100 mg or placebo at weeks 0 and 4. Patients initially assigned to placebo were switched to receive tildrakizumab at weeks 12, 16, and every 12 weeks thereafter. Patients in the tildrakizumab group continued with tildrakizumab at week 16, and every 12 weeks until week 52. The primary endpoint was the Psoriasis Area and Severity Index (PASI 75) response rate at week 12.Results::At week 12, tildrakizumab demonstrated significantly higher PASI 75 response rates (66.4% [73/110] vs. 12.7% [14/110]; difference, 51.4% [95% confidence interval (CI), 40.72, 62.13]; P <0.001) and Physician’s Global Assessment (60.9% [67/110] vs. 10.0% [11/110]; difference, 49.1% [95% CI, 38.64, 59.62]; P <0.001) compared to placebo. PASI 75 response continued to improve over time in both tildrakizumab and placebo-switching to tildrakizumab groups, reaching maximal efficacy after 28 weeks (86.8% [92/106] vs. 82.4% [89/108]) and maintained up to 52 weeks (91.3% [95/104] vs. 87.4% [90/103]). Most treatment-emergent adverse events were mild and not related to tildrakizumab. Conclusion::Tildrakizumab demonstrated durable efficacy through week 52 and was well tolerated in Chinese patients with moderate-to-severe plaque psoriasis.Trial registration::ClinicalTrials.gov, NCT05108766.

Objectives:To investigate the clinical feasibility of three-dimensional(3D)high-resolution late gadolinium enhancement(LGE)MRI in accessing left atrial myocardial fibrosis in patients with atrial fibrillation(AF). Methods:A total of 34 AF patients referred for hybrid surgical ablation were retrospectively enrolled in this study.3D-LGE-MRI images were acquired by Siemens 3.0 T machine and analyzed by ADAS post-processing software by two experienced radiologists to obtain parameters such as the area and the area percentage of LGE.Regional analysis was performed by one of the two radiologists at ten left atrial segments.The Kappa test was used to assess the agreement for scoring image quality,and the interclass correlation coefficient(ICC)was used to evaluate the interobserver agreement of LGE parameters.The parameters of left atrial morphology,area(and area percentage)of LGE,and location of LGE were compared between patients with persistent AF and paroxysmal AF. Results:Images of all 34 patients were considered to have diagnostic value.The scores of the overall image quality and the clarity of the left atrial wall evaluated by two radiologists were(2.88±0.64)points and(3.26±0.75)points(radiologist 1),(2.97±0.58)points and(3.24±0.70)points(radiologist 2),respectively.The corresponding Kappa values were 0.724 and 0.859.Both the area and the area percentage of LGE showed good consistency among observers,and the ICCs were 0.969 and 0.950,respectively.The difference in the area of LGE and the area percentage of LGE between patients with paroxysmal and persistent atrial fibrillation was similar(both P＞0.05).Compared with patients with paroxysmal AF,patients with persistent AF had a higher Utah stage and more severe myocardial fibrosis in the right inferior pulmonary vein antrum and the left atrial septum(all P＜0.05). Conclusions:3D high-resolution LGE-MRI provides a non-invasive way to visualize and quantify left atrial myocardial fibrosis.The extent of left atrial fibrosis in patients with persistent AF is more severe than that in patients with paroxysmal AF,with a preferential distribution in the right inferior pulmonary vein antrum and the left atrial septum.

Objective:To observe the efficacy of cosmetic suturing techniques combined with topical recombinant human basic fibroblast growth factor (rh-bFGF) in repairing facial trauma.Methods:A prospective study was conducted on 140 patients with facial trauma admitted to the Department of Burn and Plastic Surgery, Northern Jiangsu People＇s Hospital from January to December 2022. Patients were divided into two groups based on different treatment methods using a random number table method: treatment group (70 cases), including 38 males and 32 females aged 3 to 54 (23.1±8.2) years, received cosmetic suturing techniques combined with topical rh-bFGF for wound repair; control group (70 cases), including 36 males and 34 females aged 2 to 49 (22.3±7.5) years, only received cosmetic suturing techniques for wound repair. Patients were followed up 2 weeks post-surgery to evaluate wound healing quality. Patient satisfaction was assessed using the visual analogue scale (VAS). Six months post-surgery, scar conditions were evaluated using the Vancouver scar scale (VSS).Results:In the treatment group, 65 cases were directly sutured, and 5 cases were repaired with skin flaps, with a first-class healing rate of 100% (70/70). In the control group, 66 cases were directly sutured, and 4 cases were repaired with skin flaps, with a first-class healing rate of 91.4% (64/70). The first-class healing rate in the treatment group was higher than that in the control group, with a statistically significant difference ( P=0.037). Two weeks post-surgery, the VAS score for surgical satisfaction in the treatment group was (1.13±0.52) scores, which was lower than that in the control group (2.56±1.32) scores, with a statistically significant difference ( P<0.001). Six months post-surgery, the VSS score for the treatment group was (2.49±1.27) scores, which was lower than that in the control group (4.67±1.93) scores, with a statistically significant difference ( P<0.001). Conclusions:In repairing facial trauma, the combination of cosmetic suturing techniques and topical rh-bFGF can improve wound healing quality, reduce wound scarring, and enhance patient satisfaction with surgery.

bstract: Objective To elucidate the distribution characteristics of mosquito species and the population genetic diversity of important mosquito species in the Wuyi Mountain Nature Reserve, with the aim of providing a scientific basis for the prevention and control of mosquito-borne diseases in the region. Methods Within Wuyi Mountain Nature Reserve 2022- 2023, 16 sampling sites were selected, where larvae were collected using the pipette method and adult mosquitoes were collected using the mosquito trap lamp method. Mosquito species identification was accomplished by integrating morphological characteristics and molecular identification techniques based on CO Ⅰ and CO Ⅱ gene sequences. Software tools such as ClustalX, DnaSP v5.0, and Network v4.6.1.0 were utilized to analyze the genetic differentiation (Fst), gene flow (Nm) among populations of Aedes japonicus, Aedes albopictus and Armigeres subalbatus. Results The mosquito specimens collected from the Wuyi Mountain Nature Reserve were identified as 30 species belonging to 8 genera within the Culicidae family. Among them, there were 10 species of Aedes, 13 species of Culex, 1 species each of Armigeres, Orthopodomyia, Uranotaenia, Tripyeroides, and Anopheles, and 2 species of Toxorhynchites. Analysis of the genetic structure of important mosquito populations showed that the haplotype diversity index (Hd) of Ae. japonicus was 0.994 7, with a generally moderate degree of differentiation between populations and a higher degree of genetic differentiation between populations 6 and 12; Aedeslbopictus had a haplotype diversity index of 0.634 0, with significant genetic differentiation between populations 1 and 2 compared to other groups; Armigeres subalbatus had a haplotype diversity index of 0.703 3, with substantial genetic differentiation and limited gene flow between population 2 and populations 3, 4, 6, and 7. Conclusions The mosquito species are rich in Wuyi Mountain Nature Reserve. A comprehensive survey of the composition and distribution of mosquito populations was carried out, and the characteristics of the population genetic structure of the important species of Ae. japonicus, Ae. Albopictus, and Ar. subalbatus populations were analyzed, providing valuable scientific data reference for local mosquito-borne ecological research and disease prevention and control.

This study constructed a LHCGR-CRE-luc-HEK293 transgenic cell line according to the activation of the cAMP signaling pathway after recombinant human chorionic gonadotropin binding to the receptor. The biological activity of recombinant human chorionic gonadotropin was assayed using a luciferase assay system. The relative potency of the samples was calculated using four-parameter model. And the method conditions were optimized to validate the specificity, relative accuracy, precision and linearity of the method. The results showed that there was a quantitative potency relationship of human chorinonic gonadotropin (hCG) in the method and it was in accordance with the four-parameter curve. After optimization, the conditions were determined as hCG dilution concentration of 2.5 μg·mL^-1, dilution ratio of 1∶4, cell number of 10 000-15 000 cells/well, and induction time of 6 h. The method had good specificity, relative accuracy with relative bias ranging from -8.9% to 3.4%, linear regression equation correlation coefficient of 0.996, intermediate precision geometric coefficient of variation ranging from 3.3% to 15.0%, and linearity range of 50% to 200%. This study successfully established and validated a reporter gene method to detect hCG biological activity, which can be used for hCG biological activity assay and quality control.

Objective To study the correlation between traditional Chinese medicine(TCM)constitution and pathogenic factors in patients with ankylosing spondylitis(AS).Methods One hundred patients of AS and their family members who had medical consultation in the Fifth Hospital of Xi'an(i.e.,Shaanxi Hospital of Integrated Traditional Chinese and Western Medicine)in August 2019 and September 2020 were selected as the study subjects.The guidelines of Classification and Determination of Traditional Chinese Medicine Constitution issued by the China Association of Chinese Medicine were adopted to determine the traditional Chinese medicine(TCM)constitution types of the study subjects.The sociodemographic information,living habits,clinical symptoms,and TCM constitution types of the AS patients and their family members were collected by means of questionnaires and clinical investigations,and then the pathogenic factors of the patients with AS were investigated.The binomial Logistic regression model was used to analyze the correlation between TCM constitution types and pathogenic factors in patients with AS.Results(1)Among the 100 AS patients,the majority of them had the biased constitutions,and the biased constitutions with the occurrence frequency in descending order were yang deficiency constitution,qi deficiency constitution,and damp-heat constitution,which accounted for 33.00%,14.00%,and 18.00%,respectively.(2)The prevalence rates of AS in the first-,second-,and third-degree relatives of AS patients were 56.25%,40.00%and 25.00%,respectively.For the positive rates of human leukocyte antigen B27(HLA-B27)in AS patients and their family members,HLA-B27 in AS patients was all positive,while the positive rates of HLA-B27 in the first-,second-,and third-degree relatives of AS patients were 44.31%,30.67%and 15.63%,respectively.(3)The results of regression analysis showed that the disease duration of AS patients was significantly correlated with qi deficiency constitution,the grading of sacroiliac arthritis was correlated with qi stagnation constitution,and age was correlated with blood stasis constitution(P＜0.05 or P＜0.01).The results indicated that disease duration and age were the important factors affecting the constitution types of AS patients,and disease duration was closely related to qi deficiency while age was closely related to blood stasis.Conclusion AS is a highly hereditary autoimmune disease,and its onset is associated with HLA-B27.Yang deficiency is the basic constitution type of AS,and damp-heat constitution is the main constitution type in the progression of AS(especially in the active stage of the disease).The prolongation of the disease will exacerbate the illness condition of AS and then the manifestations of qi deficiency will be more obvious.

BACKGROUND:In recent years,there have been many novel tympanic membrane repair materials,including patches and 3D-printed scaffolds.However,the tympanic membrane repaired by these materials is different from the natural tympanic membrane in terms of thickness and internal structure. OBJECTIVE:To explore the efficacy of bone marrow mesenchymal stem cells-loaded high-porosity polycaprolactone/collagen nanofiber membrane scaffolds in repairing chronic tympanic membrane perforation. METHODS:Polycaprolactone,polycaprolactone-collagen,and high-porosity polycaprolactone-collagen nanofiber membranes were prepared by electrospinning technology,and the surface morphology,porosity and cell compatibility of the scaffolds were characterized.The tympanic membrane perforation model of 50 male SD rats was established by puncturing the posterior lower part of both eardrums with a sterile 23-measure needle combined with mitomycin C and hydrocortisone.After 12 weeks of modeling,the rats were divided into five groups by the random number table method.The blank control group did not receive any treatment.In the other four groups,polycaprolactone nanofiber membrane(polycaprolactone group),polycaprolactone-collagen nanofiber membrane(polycaprolactone-collagen group),high-porosity polycaprolactone-collagen nanofiber membrane(high-porosity polycaprolactone-collagen group)and high-porosity polycaprolactone-collagen nanofiber membrane containing bone marrow mesenchymal stem cells(high-porosity polycaprolactone-collagen group)were implanted at the perforation of the tympanic membrane,respectively.Each group consisted of 10 animals.The healing of the tympanic membrane was examined by otoendoscopy after 1,2,3 and 4 weeks of stent implantation.Hematoxylin-eosin staining,Masson staining,and Ki-67 immunohistochemical staining were performed on the tympanic membrane after 4 weeks of implantation. RESULTS AND CONCLUSION:(1)Scaffold characterization:Scanning electron microscopy showed that compared with other nanofiber membranes,the high-porosity polycaprolactone-collagen nanofiber membranes had more orderly nanofiber structure,larger surface pore size,and higher porosity(P<0.001).Live/dead staining showed that bone marrow mesenchymal stem cells adhered well on the three scaffolds,and the number of living cells on the high-porosity polycaprolactone-collagen nanofiber membrane was more than that on the other two scaffolds.Almarin staining showed that the proliferation rate of bone marrow mesenchymal stem cells on the high-porosity polycaprolactone-collagen nanofiber membrane was higher than that of the other two fiber membranes.(2)Animal experiments:Except for the blank control group,the tympanic membrane of the other four groups healed gradually with the extension of the time of fibrous membrane implantation,among which the healing speed of the cell-loaded high-porosity polycaprolactone-collagen group was the fastest.Hematoxylin-eosin staining,Masson staining,and Ki-67 immunohistochemical staining showed that the tympanic membrane of rats in the cell-carrying high-porosity polycaprolactone-collagen group was moderate in thickness and a three-layer structure with uniform collagen fiber layers,similar to the normal tympanic membrane,and the repair quality of tympanic membrane was better than that of other fiber membrane groups.(3)The results showed that the high-porosity polycaprolactone-collagen nanofiber membrane containing bone marrow mesenchymal stem cells could not only rapidly repair the perforation of the tympanic membrane,but also the newly healed tympanic membrane was similar to normal tympanic membrane in structure and thickness.

Objective:To evaluate the curative effects of 3D printed microporous titanium (tantalum) prosthesis in reconstruction of large segmental bone defects caused by lower extremity osteomyelitis.Methods:A retrospective study was conducted to analyze the clinical data of 18 patients who had been treated for large segmental bone defects caused by lower extremity osteomyelitis between January 2020 to May 2022 at Department of Orthopaedics, The 920th Hospital of Joint Logistics Support Force. There were 10 males and 8 females with an age of (45.3±14.1) years. The defects were at the left side in 13 cases and at the right side in 5 cases, at the femur in 11 cases and at the tibia in 7 cases. The duration of osteomyelitis was 1.0 (1.0, 3.5) years. The length of bone defects was 8.35 (6.50, 9.84) cm. Their bone defects were repaired by an individually 3D printed microporous titanium (tantalum) prosthesis after operative removal of osteomyelitis lesions. The wound healing was observed after surgery. The clinical efficacy was comprehensively evaluated by the Paley grading for bone defect healing, visual analog scale (VAS), lower extremity functional scale (LEFS), and imaging examination.Results:The postoperative follow-up period for the 18 patients was (12.2±0.3) months. Wound infection occurred 2 months after surgery in one patient who was treated with Ilizarov bone transfer after removal of the microporous titanium prosthesis. The remaining 17 patients had good postoperative wound healing. At the last follow-up, the 18 patients had a VAS pain score of 2.0(1.0, 4.0) points, significantly lower than the preoperative one [(6.1±2.3) points], and a LEFS score of 54.00(34.50, 69.25) points, significantly higher than the preoperative one [18.50(9.00, 26.50) points] ( P<0.05). At the last follow-up, according to the Paley grading, the bone union was rated as excellent in 16 patients, as good in 1 patient and as poor in 1 patient. The integration of femoral fractures with 3D printed microporous titanium prostheses was fine. Conclusion:In reconstruction of large segmental bone defects caused by lower extremity osteomyelitis, implantation of a 3D printed microporous titanium (tantalum) prosthesis is feasible and effective, not only reducing pain but also restoring the limb function.

Objective:This study evaluates the agreement between a new low-load sleep monitoring system, QSA600, based on millimeter-wave radar technology, and polysomnography (PSG) in diagnosing obstructive sleep apnea (OSA).Methods:A total of 155 subjects were recruited for a parallel agreement study in the sleep laboratory of the Department of Otorhinolaryngology Head and Neck Surgery at Shanghai Sixth People′s Hospital from July to September 2023. The subjects underwent simultaneous monitoring with both PSG and the QSA600 system. One hundred and forty-five subjects consisting of 75 males and 70 females included in the final analysis, with an average age of (35.30±12.41) years, an average height of (168.23±8.08) cm, and an average weight of (68.28±13.74) kg. The subjects were divided into four groups based on the apnea-hypopnea index (AHI): <5.0 events/h (non-OSA group, 39 cases), ≥5.0-<15.0 events/h (mild OSA group, 47 cases), ≥15.0-<30.0 events/h (moderate OSA group, 25 cases), and≥30.0 events/h (severe OSA group, 34 cases). Intraclass correlation coefficients (ICC), Pearson correlation coefficients ( r), and Bland-Altman analysis were employed to assess the agreement between the two monitoring techniques regarding AHI and other parameters. Sensitivity and specificity of the QSA600 in diagnosing OSA were evaluated at different AHI thresholds. Statistical analyses were conducted using MATLAB R2022a. Results:Using AHI 5 events/h, 15 events/h and 30 events/h as thresholds, the sensitivity for diagnosing mild, moderate, and severe OSA was 88.68%, 89.83% and 97.06%, respectively. The specificity was 94.87%, 98.84% and 99.10%, respectively. The areas under the receiver operating characteristic (ROC) curve was 0.973 4, 0.990 9 and 0.999 5, respectively. The comparison of key indicators between QSA600 and PSG diagnostic results revealed:a Pearson correlation coefficient of 0.987 2( P<0.001) between the AHI measurement values. The mean difference between the Bland-Altman measurement values of the two was -1.43(95% CI:-8.74-5.88) events/h and the ICC between the two was 0.985 0(95% CI: 0.975 4-0.990 4). Conclusions:As a new low-load sleep monitoring system, QSA600 demonstrates high concordance with traditional PSG in diagnosing OSA and stratifying its severity, which has promising potential for clinical application. (Clinical trial registration number: NCT06038006)