Objective:A camelid natural nanobody library was screened to target S100 calcium-binding protein B (S100B) for obtaining high-affinity and specific nanobodies (Nbs), which provided a molecular basis for the early diagnosis and prognostic treatment of malignant melanoma.Methods:In this study, affinity panning was employed to isolate S100B-specific nanobodies with unique complementarity-determining region 3 (CDR3) sequences from a camelid natural nanobody library. The selected Nbs were expressed in a prokaryotic system and purified via Ni-NTA affinity chromatography. The affinity, specificity, and diagnostic potential of the Nbs were evaluated using enzyme-linked immunosorbent assay (ELISA), western blot, and bio-layer interferometry (BLI).Results:A camelid natural anti-S100B nanobody library with a capacity of 1.91×10 8 CFU was successfully constructed. Affinity panning yielded 30 S100B-specific Nbs, among which Nb107, Nb122, Nb212, and Nb324 with distinct CDR3 sequences were selected for expression. Following Ni-NTA purification, all four anti-S100B Nbs exhibited high purity. Western blot analysis confirmed their ability to recognize recombinant S100B. ELISA and BLI analyses revealed that Nb212 demonstrated high affinity (1.96×10 -11 mol). Additionally, Nb107, Nb122, and Nb212 exhibited broad-spectrum recognition capabilities, binding to various tumor cell lines (Hepa1-6, GL261, 4T1, CT26) as well as murine/human melanoma cells. These Nbs also effectively bound to native murine/human antigens in serum samples from melanoma (A375, B16F10) mouse models. Conclusions:Specific anti-S100B Nbs are successfully screened and expressed, demonstrating not only recognition of native conformational antigens but also broad-spectrum binding and high affinity. These findings highlight their significant potential for developing early diagnostic assays and broad-spectrum targeted vaccines or therapeutics against diverse tumor cells.

Objective:A camelid natural nanobody library was screened to target S100 calcium-binding protein B (S100B) for obtaining high-affinity and specific nanobodies (Nbs), which provided a molecular basis for the early diagnosis and prognostic treatment of malignant melanoma.Methods:In this study, affinity panning was employed to isolate S100B-specific nanobodies with unique complementarity-determining region 3 (CDR3) sequences from a camelid natural nanobody library. The selected Nbs were expressed in a prokaryotic system and purified via Ni-NTA affinity chromatography. The affinity, specificity, and diagnostic potential of the Nbs were evaluated using enzyme-linked immunosorbent assay (ELISA), western blot, and bio-layer interferometry (BLI).Results:A camelid natural anti-S100B nanobody library with a capacity of 1.91×10 8 CFU was successfully constructed. Affinity panning yielded 30 S100B-specific Nbs, among which Nb107, Nb122, Nb212, and Nb324 with distinct CDR3 sequences were selected for expression. Following Ni-NTA purification, all four anti-S100B Nbs exhibited high purity. Western blot analysis confirmed their ability to recognize recombinant S100B. ELISA and BLI analyses revealed that Nb212 demonstrated high affinity (1.96×10 -11 mol). Additionally, Nb107, Nb122, and Nb212 exhibited broad-spectrum recognition capabilities, binding to various tumor cell lines (Hepa1-6, GL261, 4T1, CT26) as well as murine/human melanoma cells. These Nbs also effectively bound to native murine/human antigens in serum samples from melanoma (A375, B16F10) mouse models. Conclusions:Specific anti-S100B Nbs are successfully screened and expressed, demonstrating not only recognition of native conformational antigens but also broad-spectrum binding and high affinity. These findings highlight their significant potential for developing early diagnostic assays and broad-spectrum targeted vaccines or therapeutics against diverse tumor cells.

Sepsis is one of the common severe diseases caused by the dysregulated host response to infection， which seriously threatens the life and health of human beings all over the world. The incidence and mortality of the disease are extremely high， and it has always been an urgent problem to be solved in the field of acute and critical diseases. At present， anti-infection， fluid resuscitation， mechanical ventilation and other programs are most used in clinic to treat sepsis， but their poor prognosis and high cost and other issues remain to be resolved. Therefore， it is necessary to explore a new， efficient， safe and inexpensive drug and treatment model at this stage. The treatment of traditional Chinese medicine （TCM） is based on syndrome differentiation and holistic concept. It can effectively regulate the progression of sepsis， maintain the homeostasis of the body， and has fewer adverse reactions. It has achieved good clinical results. In recent years， a large number of studies have shown that TCM can reduce the inflammatory response by regulating the Toll-like receptor 4（TLR4） signaling pathway， thereby reducing the severity and mortality of sepsis patients. However， there is still a lack of systematic exposition of TCM regulating TLR4 signaling pathway in the treatment of sepsis. Therefore， this article summarizes the relationship between TLR4 signaling pathway and sepsis and the mechanism of TCM in the disease by searching and consulting relevant literature in recent years. It is found that some Chinese medicine monomers and active ingredients， Chinese medicine compounds and Chinese medicine preparations can effectively reduce systemic inflammatory response， repair organ damage and improve the prognosis of sepsis by inhibiting the activation of TLR4 signaling pathway. However， due to various limitations， some studies have directly focused on the differential expression and function of TLR4， ignoring the downstream molecular expression and phenotypic effects of TLR4. The alternative mechanism， relationship and specific molecular mechanism of the pathway are still unclear. There are problems such as unclear pharmacokinetics and unclear mechanism in the pro- and anti-inflammatory balance， which need to be further studied and explored in order to provide new ideas for the potential treatment and drug development for sepsis.

Sepsis is a life-threatening Organ Dysfunction disease caused by the dysregulated response of the body to infection.It is characterized by fever,chills,shortness of breath,altered consciousness,and even severe complications such as Multiple Organ Dysfunction Syndrome(MODS).The morbidity and mortality of this disease are high year after year,and there are problems such as large consumption of medical resources and poor prognosis,which seriously affect the quality of life and economic burden of patients.Therefore,it is important to explore new treatments with high efficiency,safety and low cost.The disease pathogenesis is complex,including inflammation imbalance is the main pathogenesis of sepsis.Mitogen-Activated Protein Kinases(MAPK)signaling pathway is a signaling pathway activated by environmental factors or inflammatory factors,which mediates proliferation,differentiation,inflammatory response and apoptosis,and plays a key role in the occurrence and development of sepsis.At present,antibiotics,fluid resuscitation and mechanical ventilation are the main methods for clinical treatment of sepsis.Although they can curb the progress of some diseases,some treatment effects are not good.A large amount of literature has confirmed that Chinese medicine intervention in sepsis has significant advantages,its through many channels,regulation and control of multiple targets,MAPK signaling pathways,inhibit inflammation,strengthening immune defense and effective in the treatment of sepsis,sepsis is current research hotspot.However,there is still a lack of systematic reviews on the regulation of MAPK signaling pathway by traditional Chinese medicine in the treatment of sepsis.Therefore,based on the retrieval database sepsis related literature at home and abroad in recent years,a systemic summary of MAPK signal pathway and sepsis relations and the role of traditional Chinese medicine in them,will be new drugs for the treatment of sepsis and development provides new theoretical support.

Sepsis is a life-threatening Organ Dysfunction disease caused by the dysregulated response of the body to infection.It is characterized by fever,chills,shortness of breath,altered consciousness,and even severe complications such as Multiple Organ Dysfunction Syndrome(MODS).The morbidity and mortality of this disease are high year after year,and there are problems such as large consumption of medical resources and poor prognosis,which seriously affect the quality of life and economic burden of patients.Therefore,it is important to explore new treatments with high efficiency,safety and low cost.The disease pathogenesis is complex,including inflammation imbalance is the main pathogenesis of sepsis.Mitogen-Activated Protein Kinases(MAPK)signaling pathway is a signaling pathway activated by environmental factors or inflammatory factors,which mediates proliferation,differentiation,inflammatory response and apoptosis,and plays a key role in the occurrence and development of sepsis.At present,antibiotics,fluid resuscitation and mechanical ventilation are the main methods for clinical treatment of sepsis.Although they can curb the progress of some diseases,some treatment effects are not good.A large amount of literature has confirmed that Chinese medicine intervention in sepsis has significant advantages,its through many channels,regulation and control of multiple targets,MAPK signaling pathways,inhibit inflammation,strengthening immune defense and effective in the treatment of sepsis,sepsis is current research hotspot.However,there is still a lack of systematic reviews on the regulation of MAPK signaling pathway by traditional Chinese medicine in the treatment of sepsis.Therefore,based on the retrieval database sepsis related literature at home and abroad in recent years,a systemic summary of MAPK signal pathway and sepsis relations and the role of traditional Chinese medicine in them,will be new drugs for the treatment of sepsis and development provides new theoretical support.

The treatment of patients with diabetes mellitus, which is characterized by defective insulin secretion and/or the inability of tissues to respond to insulin, has been studied for decades. Many studies have focused on the use of incretin-based hypoglycemic agents in treating type 2 diabetes mellitus (T2DM). These drugs are classified as GLP-1 receptor agonists, which mimic the function of GLP-1, and DPP-4 inhibitors, which avoid GLP-1 degradation. Many incretin-based hypoglycemic agents have been approved and are widely used, and their physiological disposition and structural characteristics are crucial in the discovery of more effective drugs and provide guidance for clinical treatment of T2DM. Here, we summarize the functional mechanisms and other information of the drugs that are currently approved or under research for T2DM treatment. In addition, their physiological disposition, including metabolism, excretion, and potential drug-drug interactions, is thoroughly reviewed. We also discuss similarities and differences in metabolism and excretion between GLP-1 receptor agonists and DPP-4 inhibitors. This review may facilitate clinical decision making based on patients' physical conditions and the avoidance of drug-drug interactions. Moreover, the identification and development of novel drugs with appropriate physiological dispositions might be inspired.

OBJECTIVE: To compare the biomechanical differences among the five internal fixation modes in treatment of Day type Ⅱ crescent fracture dislocation of pelvis (CFDP), and find an internal fixation mode which was the most consistent with mechanical principles. METHODS: Based on the pelvic CT data of a healthy adult male volunteer, a Day type Ⅱ CFDP finite element model was established by using Mimics 17.0, ANSYS 12.0-ICEM, Abaqus 2020, and SolidWorks 2012 softwares. After verifying the validity of the finite element model by comparing the anatomical parameters with the three-dimensional reconstruction model and the mechanical validity verification, the fracture and dislocated joint of models were fixed with S ₁ sacroiliac screw combined with 1 LC-Ⅱ screw (S ₁+LC-Ⅱ group), S ₁ sacroiliac screw combined with 2 LC-Ⅱ screws (S ₁+2LC-Ⅱ group), S ₁ sacroiliac screw combined with 2 posterior iliac screws (S ₁+2PIS group), S ₁ and S ₂ sacroiliac screws combined with 1 LC-Ⅱ screw (S ₁+S ₂+LC-Ⅱ group), S ₂-alar-iliac (S ₂AI) screw combined with 1 LC-Ⅱ screw (S ₂AI+LC-Ⅱ group), respectively. After each internal fixation model was loaded with a force of 600 N in the standing position, the maximum displacement of the crescent fracture fragments, the maximum stress of the internal fixation (the maximum stress of the screw at the ilium fracture and the maximum stress of the screw at the sacroiliac joint), sacroiliac joint displacement, and bone stress distribution around internal fixation were observed in 5 groups. RESULTS: The finite element model in this study has been verified to be effective. After loading 600 N stress, there was a certain displacement of the crescent fracture of pelvis in each internal fixation model, among which the S ₁+LC-Ⅱ group was the largest, the S ₁+2LC-Ⅱ group and the S ₁+2PIS group were the smallest. The maximum stress of the internal fixation mainly concentrated at the sacroiliac joint and the fracture line of crescent fracture. The maximum stress of the screw at the sacroiliac joint was the largest in the S ₁+LC-Ⅱ group and the smallest in the S ₂AI+LC-Ⅱ group. The maximum stress of the screw at the ilium fracture was the largest in the S ₁+2PIS group and the smallest in the S ₁+2LC-Ⅱ group. The displacement of the sacroiliac joint was the largest in the S ₁+LC-Ⅱ group and the smallest in the S ₁+S ₂+LC-Ⅱ group. In each internal fixation model, the maximum stress around the sacroiliac screws concentrated on the contact surface between the screw and the cortical bone, the maximum stress around the screws at the iliac bone concentrated on the cancellous bone of the fracture line, and the maximum stress around the S ₂AI screw concentrated on the cancellous bone on the iliac side. The maximum bone stress around the screws at the sacroiliac joint was the largest in the S ₁+LC-Ⅱ group and the smallest in the S ₂AI+LC-Ⅱ group. The maximum bone stress around the screws at the ilium was the largest in the S ₁+2PIS group and the smallest in the S ₁+LC-Ⅱ group. CONCLUSION For the treatment of Day type Ⅱ CFDP, it is recommended to choose S ₁ sacroiliac screw combined with 1 LC-Ⅱ screw for internal fixation, which can achieve a firm fixation effect without increasing the number of screws.
Adult ; Male ; Humans ; Finite Element Analysis ; Fracture Fixation, Internal/methods* ; Fractures, Bone/surgery* ; Pelvis ; Spinal Fractures/surgery* ; Fracture Dislocation/surgery* ; Joint Dislocations/surgery* ; Biomechanical Phenomena

Objective: To investigate the awareness of HIV non-occupational post-exposure prophylaxis (nPEP) among residents in Yangzhou City, Jiangsu Province, so as to provide basis for further publicity and application of nPEP in genenral population. Methods: Community residents at ages of 18 years and older in Yangzhou City were sampled using the multi-stage random sampling method from January to June, 2022, and a cross-sectional survey was conducted to collect their demographic information, acquired immune deficiency syndrome (AIDS)-related knowledge, attitude and behaviors and awareness of nPEP. A multivariable logistic regression model was used to identify factors affecting awareness of nPEP. Results: Totally 1 488 questionnaires were allocated, and 1 447 valid questionnaires were recovered, with an effective recovery rate of 97.24%. There were 644 males and 803 females, with mean age of (36.33±11.90) years. There were 585 residents (40.43%) employed by government agencies, enterprises and public institutions; 750 residents (51.83%) with awareness of AIDS; 413 (28.54%), 651 (44.99%) and 383 residents (26.47%) had low, medium and high levels of AIDS discrimination, respectively; 201 residents (13.89%) with HIV detection experience; and 792 residents (54.73%) with regular health checkup. The awareness rate of nPEP was 47.89%. Multivariable logistic regression analysis identified career (government agencies, enterprises and public institutions, OR=1.530, 95%CI: 1.170-1.999; students, OR=1.450, 95%CI: 1.027-2.047), awareness of AIDS (OR=3.201, 95%CI: 2.495-4.106), having HIV detection experience (OR=1.908, 95%CI: 1.339-2.719), regular health checkup (OR=2.308, 95%CI:1.807-2.949) and discrimination against AIDS (medium, OR=0.703, 95%CI: 0.532-0.928; high, OR=0.699, 95%CI: 0.502-0.974) as factors affecting awareness of nPEP. Conclusions The awareness of nPEP among residents in Yangzhou City needs to be improved. Employees in government agencies, enterprises and public institutions and students have higher awareness of nPEP.