Traditional treatment for type 1 diabetes mellitus （T1DM） primarily involves insulin replacement， yet some patients encounter issues such as significant blood glucose fluctuations， high risk of hypoglycemia， and weight gain. In recent years， the adjuvant therapeutic role of non-insulin hypoglycemic drugs in T1DM has gradually gained attention. This article reviews the mechanisms of action and clinical research progress of five types of non-insulin hypoglycemic drugs in the treatment of T1DM： amylin analogues （pramlintide）， biguanides （metformin）， sodium-glucose co-transporter 2 inhibitor， dipeptidyl peptidase-4 inhibitor， and glucagon-like peptide-1 receptor agonist. It is found that these drugs can enhance clinical benefits for T1DM patients by improving insulin sensitivity， delaying gastric emptying， promoting urinary glucose excretion， and regulating incretin levels， thereby reducing glycated hemoglobin levels， decreasing insulin dosage， and managing body weight. Simultaneously， these drugs also present limitations such as low patient compliance due to complex dosing regimens， increased risk of diabetic ketoacidosis， and heterogeneity in glycemic control. Future research could focus on developing individualized treatment strategies， combining pharmacogenomics with novel biomarkers to precisely identify subpopulations of patients who may benefit， and delving into the potential value of these drugs in delaying diabetic vascular complications and improving patients’ quality of life.

Hemophilia A and hemophilia B are hereditary coagulation bleeding disorders. Traditional treatment primarily relies on factor replacement therapy using coagulation factor Ⅷ(FⅧ) or coagulation factor Ⅸ (FⅨ)products. Although conventional therapies can alleviate bleeding symptoms to some extent, they also have certain limitations, such as the need for frequent infusions, the risk of infection, and the potential development of inhibitors in some patients. Currently, treatment strategies for hemophilia are gradually shifting toward non-factor therapies, providing the appearence of novel non-factor drugs. However, these novel therapies not only interfere with traditional coagulation assays but may also fail to comprehensively evaluate their efficacy and safety through conventional coagulation tests. Therefore, there is an urgent need to develop and optimize new laboratory testing methods to ensure accurate assessment of patients′ responses to non-factor therapies and the hemostatic capacity of the drugs themselves. Although some studies have explored the coagulation factor equivalence of non-factor agents, such equivalence cannot fully reflect the actual hemostatic effect in patients after treatment and is therefore unsuitable as a prognostic indicator. Compared with assessing coagulation factor equivalence, total coagulation assays, such as the thrombin generation assay (TGA), can more accurately evaluate efficacy and safety. TGA can take into account multiple factors in the coagulation process, providing a more comprehensive assessment of coagulation function. Furthermore, combining TGA with patient symptoms for comprehensive analysis can enhance its prognostic predictive ability, offering more reliable support for clinical decision-making.

Objective:To analyze the levels of thrombin generation and activated protein C resistance (APC-R) in lupus anticoagulant (LA)-positive patients, and to assess their effectiveness in predicting thrombotic risk in these patients.Methods:Retrospective case-control study. A total of 185 patients with positve LA [91 males, 94 females; age (47.59±19.14) years] in Ruijin Hospital of Shanghai Jiaotong University School of Medicine from November 1st, 2024 to March 31st, 2025 were included. Patients were stratified into thrombotic ( n=91) and non-thrombotic groups ( n=94) based on clinical diagnosis and imaging evidence of thrombosis. The basic characteristics and routine laboratory coagulation levels of LA-positive patients were analyzed. Post-test plasma samples were collected from 43 cases with positive or strongly positive LA, categorized into thrombotic ( n=23) and non-thrombotic ( n=20) groups. Additionally, plasma was collected from 80 healthy controls [40 males and 40 females, age (38.37±15.74) years]. Using simple random sampling method, plasma samples from 10 selected males and 10 selected females were mixed to make 1 group of healthy control, thus accordingly resulted in a total of 4 healthy control groups. Thrombin generation assays (TGA) were then employed to measure prothrombin generation and activated protein C resistance (APC-R) levels in the healthy control, non-thrombotic, and thrombotic groups. One-way analysis of variance was utilized to compare thrombin generation and APC-R levels across these groups. Results:Among the routine laboratory coagulation indexes, the median levels of activated partial thromboplastin time (APTT), fibrin degradation product (FDP) and protein C (PC) in thrombotic group were 30.9 (28.8, 35.5) s, 2.5 (1.3, 2.8) mg/L, and 107.0 (93.0, 127.0)%, respectively, which were significantly higher compared with the non-thrombosis group (all P<0.05). However, between the thrombotic and non-thrombotic group, no statistically significant differences were observed for the levels of prothrombin time (PT), thrombin time (TT), fibrinogen (Fg), or D-dimer (D-D) ( P>0.05). The TGA results showed that the total thrombin generation, the maximal thrombin generation and APC-R levels of patients in the thrombotic group were (1 118.72±387.34) nmol/L·min, (106.01±59.00) nmol/L and (0.33±0.22), respectively, which were significantly higher compared with those in the non-thrombotic group (all P<0.05). Conclusion:Significantly increased thrombin generation and enhanced APC-R were present in the LA-positive patients with thrombosis, indicating the important values of thrombin generation and APC-R in assessing thrombosis risk among this population.

Objective:To compare the accuracy of one-stage clotting assay and chromogenic substrate assay for testing an extended half-life recombinant FⅧ and to explore standardized conversion models between methods.Methods:Observational study. FⅧ activity (FⅧ:C) in plasma samples with theoretical values of 1 000, 800, 600, 500, 400, and 300 IU/L was measured using both one-stage clotting assay (employing Siemens Actin FSL reagent, Werfen SynthASil reagent, Stago PTT-A reagent) and the chromogenic substrate assay from Hyphen Biomed. Differences in FⅧ:C measured by the various methods were compared using the SNK test. Recovery rates were calculated to evaluate the accuracy of each assay. Sample activity was verified using the thrombin generation assay (TGA). Correlations between activities determined by the different assay systems were assessed using linear regression analysis.Results:Observational study. FⅧ activity (FⅧ:C) in diluted plasma samples with theoretical values of 1 000, 800, 600, 500, 400, and 300 IU/L was measured using both one-stage clotting assay (employing Siemens Actin FSL reagent, Werfen SynthASil reagent, Stago PTT-A reagent) and the chromogenic substrate assay from Hyphen Biomed. Differences in FⅧ:C measured by the various methods were compared using the SNK test. Recovery rates were calculated to evaluate the accuracy of each assay. Sample activity was verified using the thrombin generation assay (TGA). Correlations between activities determined by the different assay systems were assessed using linear regression analysis.Conclusion:Some marked one-stage clotting assay system has limitations in the clinical detection of extended half-life recombinant FⅧ. While the chromogenic substrate assay provides more accurate results. The one-stage clotting assay values can undergo cross-assay correction for FⅧ:C using a standardized conversion coefficient, which can further elevate the accuracy of monitoring hemophilia treatment efficacy.

Congenital coagulation factor Ⅶ deficiency is a rare autosomal incomplete recessive disorder caused by a defect in the coagulation factor Ⅶ (FⅦ) gene, with an incidence of approximately 1 in 500 000. Antiphospholipid antibody syndrome is relatively common and is a common cause of acquired thrombosis. However, the combination of the latter and the former is extremely rare in clinical practice, which brings difficulties to diagnosis and treatment. This article reported the laboratory examination, diagnosis and treatment of a patient with congenital coagulation factor Ⅶ deficiency and antiphospholipid syndrome after portal vein thrombosis, and reviewed the relevant literature.

A 64-year-old male patient with hemophilia A was scheduled for the surgical removal of a pulmonary mass. Preoperative evaluation revealed that the coagulation factor Ⅷ (FⅧ) activity was 0.5%, with an F Ⅷ inhibitor level of 32 BU/ml; the R value could not be detected on the thromboelastogram. Thoracoscopic lobectomy was successfully completed. On the day of the operation and the first day after the operation, 6 mg of recombinant activated coagulation factor Ⅶ (rFⅦa) was intravenously administered every 6 h. On postoperative day 1, the patient’s blood pressure dropped and the HGB gradually declined from 102 g/L to 65 g/L. Chest X-ray revealed a large amount of pleural effusion on the left side, and urgent thoracoscopic thoracic exploration was performed. A total of 3200 mL fresh blood was cleared, and a thoracic drainage tube was placed. On postoperative day 2, the rFⅦa dose was increased to 6 mg, which was intravenously administered every 4 h, and concentrated red cells were intermittently infused to correct anemia. Four days later, due to the inability to obtain rFⅦa, PCC (50 IU/kg every 8 hours) was administered. Additionally, treatment with methylprednisolone (40 mg/d) and cyclophosphamide (200 mg, every 2 weeks) was initiated to remove FⅧ inhibitors. The thoracic drainage tube was removed on postoperative day 9, and the patient was successfully discharged 3 weeks later.

Objective:To analyze and predict the biological properties and function of Treponema pallidum OmpH protein by bioinformatics methods, purify the target protein, and prepare polyclonal antibodies. Methods:From January 2024 to February 2025, the research team from the Department of Clinical Laboratory at The First Affiliated Hospital of Hunan Traditional Chinese Medical College (Hunan Province Directly Affiliated Traditional Chinese Medical Hospital) conducted a study employing integrative approaches combining bioinformatics analysis with animal experimentation. During this investigation, the coding sequence of the T. pallidum outer membrane protein H (TpOmpH) was systematically retrieved from the National Center for Biotechnology Information (NCBI) database. And the bioinformatics tools, such as Protparam, Protscale,SignalP 6.0,NetNGlyc-1.0,TMHMM2.0,NetPhos-3.1,SOPMA,AlphaFold3,IEDB,STRING,C-immsim were used to analyze and predict the biological and immunological characteristics of TpOmpH protein. The full length of TpOmpH gene was synthesized and was cloned into the pET28a to construct the recombinant plasmid pET28a-TpOmpH. The the expression of target protein was induced by IPTG and was purified using affinity chromatography. The TpOmpH protein was used to immunize mice and the anti-serum was harvested, then the titer of antibody was detected. Results:TpOmpH is a hydrophobic outer membrane protein with a molecular weight of 19.7 kDa and strong stability. The TpOmpH protein is located outside the cell membrane and contains 11 serine, 4 threonine, and 1 tyrosine phosphorylation site, but no glycosylation sites. The 77.91% of the amino acids in TpOmpH protein are alpha helix, 8.72% are extended strand, 10.47% are random coils, and 2.91% are beta turns. The tertiary structure predicted by AlphaFold3 is in its optimal state. The TpOmpH protein has 4 CTL epitopes, 4 linear epitopes, and 5 spatial epitopes. The TpOmpH protein can interact with Tp92,MutS,SurA,TPANIC_0600 and other proteins which may be involved in Tp invasion. TpOmpH protein can induce an increase in B cell count, antibody content, Th cell count, NK cell count, as well as the expression of various cytokines. High purity TpOmpH protein was obtained through Ni 2+ affinity chromatography, which is consistent with the theoretical molecular weight. TpOmpH protein can induce mice to secrete polyclonal antibodies with antibody titers higher than 1∶10 000. Conclusion:TpOmpH protein is a hydrophobic protein located on the outer membrane of Tp, can induce mice to secrete high titer antibodies, which providing experimental basis for the pathogenesis of Tp and vaccine development.

Objective:To quickly identify the causes of morphological abnormalities of microcytic hypochromic erythrocytes that are detected during health checkups for recruitment of flying cadets, and to explore its role in medical selection.Methods:Students with hemoglobin (Hb)≥110 g/L and morphological abnormalities of microcytic hypochromic erythrocytes detected during the 2023 medical selection of flying cadets by Guangzhou Selection Center were selected. Their medical history was collected, and iron metabolism, Hb electrophoresis and hemoglobin H (HbH) inclusion bodies were examined to screen for thalassemia and iron deficiency. The diagnosis of thalassemia was confirmed by thalassemia gene testing. Those with iron deficiency received iron supplementation therapy and the recovery of Hb was observed.Results:Ninety-one students were diagnosed with Hb≥110 g/L and morphological abnormalities of microcytic hypochromic erythrocytes, accounting for 4.35% of the total. Among these cases, 85 with abnormal Hb electrophoresis and/or positive HbH inclusion body detection were confirmed as thalassemia minor via thalassemia genetic testing, and 3 cases with normal iron metabolism, Hb electrophoresis, and negative HbH inclusion body detection. A total of 88 cases of thalassemia minor were diagnosed, accounting for 96.70% of the total. Among them, 2 cases were complicated with iron deficiency while 3 were diagnosed with iron deficiency erythropoiesis. Out of the 91 students with Hb≥110 g/L and morphological abnormalities of microcytic hypochromic erythrocytes, 9 were recruited, including 7 cases with thalassemia minor (Hb≥130 g/L), 1 case with thalassemia minor combined with iron deficiency erythropoiesis (Hb≥130 g/L after iron supplementation), and 1 case with iron deficiency erythropoiesis (Hb≥130 g/L after iron supplementation). Among the 9 recruits, 8 were followed up for over one year and the results of their military physical fitness tests all reached or exceeded the standards, but the remaining one dropped out and lost contact.Conclusions:Among physical examinees during medical selection of flying cadets in South China, thalassemia is the leading cause of morphological abnormalities of microcytic hypochromic erythrocytes. Results of iron metabolism, Hb electrophoresis, and HbH inclusion body detection can help identify thalassemia and iron deficiency quickly. Cases of morphological abnormalities of microcytic hypochromic erythrocytes caused by iron deficiency can be considered eligible for selection after Hb levels return to normal following iron supplementation therapy. Students who are diagnosed with thalassemia with Hb<130 g/L can be determined as ineligible. Such rapid identification can facilitate the medical selection of the above 2 types of students.

Objective To investigate the diagnostic efficacy of targeted biopsy(TB)combined with ipsilateral hemiglandular systematic biopsy(SB)of the dominant lesion,so as to explore a novel reduced-core biopsy strategy.Methods A retrospective analysis was conducted on the clinical data of 299 patients treated in our hospital during Sep.1,2022,and Feb.28,2023,who had a Prostate Imaging Reporting and Data System(PI-RADS)score ≥3 and underwent combined TB and SB.The dominant lesion was defined as the lesion with the highest PI-RADS score on multi-parametric magnetic resonance imaging(mpMRI);in cases of identical scores,the largest was designated as the dominant.SB was categorized as ipsilateral(ipsi-SB)or contralateral(contra-SB)to the dominant lesion.The consistency in detecting clinically significant prostate cancer(csPCa)was compared between TB with ipsi-SB(TB+ipsi-SB),TB with contra-SB(TB+contra-SB),and TB with SB(TB+SB).Subgroup analyses were performed based on PI-RADS score,prostate-specific antigen(PSA)level,prostate volume(PV),and mpMRI lesion distribution to evaluate csPCa detection rates across different variables.Results TB+ipsi-SB demonstrated comparable detection rate to TB+SB(46.2％vs.46.8％).The K values for TB+ipsi-SB and TB+contra-SB relative to TB+SB were 0.987(95％CI:0.969-1.000,P＜0.01)and 0.933(95％CI:0.892-0.974,P＜0.01),respectively.Across all subgroups,TB+ipsi-SB showed the highest agreement with TB+SB.Notably,in subgroups with PI-RADS 3 and 5,PSA＞0-20 ng/mL,PV＜25 mL,bilateral or multiple mpMRI lesions,TB+ipsi-SB achieved complete concordance with TB+SB in csPCa detection[K=1.000(95％CI:1.000-1.000),P＜0.01].Conclusion For patients with PI-RADS score ≥3,TB+ipsi-SB exhibits near-perfect consistency with TB+SB in csPCa detection while requiring fewer biopsy cores.TB+ipsi-SB represents a promising refinement of the TB+SB approach.

This study identified the types and pathogen carrying status of fleas on the surface of sheep in some areas of southern Xinjiang,and analyzed the genetic evolution differences with respect to related pathogens.The aim was to provide a reference for the local prevention and control of fleas and insect borne infectious diseases.A total of 1 586 fleas were collected from agricultural and pas-toral areas of Tumushuke City and Hotan Prefecture.Flea species were identified on the basis of morphology and the Pulex irritans mi-tochondrial COII gene.Flea DNA was extracted,and PCR was conducted to amplify the Bartonella gltA gene;Arsenophonus,Ana-plasma,Ehrlichia,and Wolbachia 16S rRNA genes;RickettsiaOmpA,17kDa,16S rRNA genes,and Yersinia pestis 16S rDNA gene.The amplified products were sequenced,and the homology of the genes of the three detected pathogens(gltA gene of Bartonella,16S rRNA gene of Wolbachia,and Anaplasma phagocytophilum)with respect to known corresponding genes of the same pathogen in Gen-Bank was analyzed.Phylogenetic trees were constructed with the adjacency method in MEGA 11.0.According to morphological and mo-lecular biology identification results,all fleas collected in this study were Pulex irritans.PCR indicated that the target gene fragments had been added to the mitochondrial COII,BartonellagltA,Wolbachia,and autophagosomal 16S rRNA genes of human fleas,all of which were consistent with the expected fragment sizes.Target bands were not amplified from Ehrlichia,Arsenophonus,spotted fever group Rickettsia,and Yersinia pestis.According to homology and genetic evolution analysis of human flea mitochondrial COII and the corresponding genes of the above-described pathogens,the COX2 gene(ON455234.1)of human fleas in Tumushuke city and Iran ob-tained in this study showed the highest homology(99.84%).The COII gene(NC_063709.1)of human fleas in Hetan City and Hunan region showed the highest homology(100%).Our findings further confirmed that the flea species was Pulex irritans.The PCR amplifi-cation results indicated that the collected Pulex irritans carried multiple pathogens,among which Bartonella and Wolbachia had the highest infection rates,and the infection rate with Anaplasma phagocytophilum was relatively low.This study is the first to discover flea species on the surface of sheep in some areas of southern Xinjiang.Our findings preliminarily confirmed that Bartonella,Wolba-chia,and Anaplasma phagocytophilum are the main Pulex irritans pathogens.