Patients with inflammatory bowel disease (IBD) require long-term pharmacotherapy. Due to the wide variety of clinically available drugs, medication safety has become increasingly concerning. As an indispensable component of pharmaceutical formulations, drug excipients may induce various adverse reactions, including rash, allergic responses, and gastrointestinal discomfort, and may even lead to severe organic injury. However, they are often overlooked in clinical practice. Therefore, identifying and managing excipient-related adverse reactions is crucial for ensuring medication safety. To address this issue, this article systematically reviews common excipients in IBD therapeutics, the underlying mechanisms of excipient-induced adverse reactions, and corresponding management strategies, aiming to enhance clinicians' awareness of excipient-related issues, improve their ability to recognize and manage such reactions, and ultimately ensure patient safety.

Cardiac troponin I (cTnI), a widely used biomarker for assessing cardiovascular risk, can provide a window for the evaluation of drug-induced myocardial injury. Label-free biosensors are promising candidates for detecting cell secretomes, since they do not require labor-intensive processes. In this work, a label-free electrochemical aptasensor is developed for in situ monitoring of cardiac cell secretomes in cell culture media based on target-induced strand displacement. The aptasensing system contains an aptamer-functionalized signal nanoprobe facing trimetallic metal-organic framework nanosheets and a gold nanoparticle-based detection working electrode modified with DNA nanotetrahedron-based complementary DNA for indirect target detection. The signal nanoprobes (termed CAHA) consisted of copper-based metal-organic frameworks, AuPt nanoparticles, horseradish peroxidase, and an aptamer. When the aptasensor is exposed to cardiac cell secretomes, cTnI competitively binds to the aptamer, resulting in the release of signal nanoprobes from the biorecognition interface and electrochemical signal changes. The aptasensor exhibited rapid response times, a low detection limit of 0.31 pg/mL, and a wide linear range of 0.001-100 ng/mL. We successfully used this aptasensor to measure cTnI concentrations among secreted cardiac markers during antitumor drug treatment. In general, aptasensors can be used to monitor a variety of cardiac biomarkers in the evaluation of cardiotoxicity.

Objective: To perform transient transfection of recombinant human Factor X(rhFX) into HEK293 cells,to optimize transfection parameters,to develop a high-yield in vitro expression system for rhFX production,and to assess the biological activity of expressed rhFX. Methods: The eukaryotic expression vector pcDNA3. 1-EGFP-FX was constructed by inserting the F10 gene into pcDNA3. 1-EGFP and subsequently transfected into HEK293cells to validate the transfection system efficiency. The recombinant expression vector pcDNA3. 1-FX was generated through ligation of the F10 gene fragment with pcDNA3. 1, followed by liposome-mediated transfection into HEK293 cells. The expression of rhFX in the cell supernatant was analyzed by Western blot and sodium dodecyl sulfate-polyacrylamide gel electrophoresis(SDS-PAGE). Transfection conditions were systematically optimized,and rhFX concentration was quantified by enzyme-linked immunosorbent assay(ELISA). The coagulation bioactivity of rhFX was evaluated through prothrombin time(PT) assay and chromogenic substrate method. Results: rhFX was successfully expressed in the supernatant of HEK293 cells. rhFX was successfully expressed in the supernatant of HEK293 cells. The highest expression level of rhFX was achieved on the third day after transfection when the cell density was 80% and the ratio of plasmid DNA to polyethyleneimine(PEI) transfection reagent was 1 ∶ 2.Triplicate ELISA measurements demonstrated a maximum rhFX concentration of 5. 20 ng/mL in the supernatant.The prothrombin time(PT) of rhFX-containing supernatant was significantly shorter(P 50) of etoxaban was determined to be 1. 449 nmol/L using the chromogenic substrate method based on rhFX,which was in the same order of magnitude as the reported 0. 78 nmol/L in the literature. Conclusion HEK293cells successfully express biologically active recombinant human Factor X(rhFX) protein,laying a foundation for advancing the development of rhFX-based therapeutics.

The contents of Zhang Zhongjing's works Treatise on Exogenous Febrile Disease,the Jade Case Classic of the Golden Cabinet,and Essentials from the Golden Cabinet(collectively known as the three classical medical books of Zhang Zhongjing),as well as Important Formulas Worth A Thousand Gold Pieces and Supplement to"Important Formulas Worth a Thousand Gold Pieces",which were cited in the Arcane Essentials from the Imperial Library(Wai Tai Mi Yao Fang)during comparative proofreading were analyzed.Wai Tai Mi Yao Fang is a book edited and public by the Bureau of Revising Medical Books in Northern Song Dynasty.The contents in the collation records for Wai Tai Mi Yao Fang were compared to the original text of the above five classical medical books proofread in Song Dynasty.The results showed that:(1)the ministers of Song Dynasty which were in charge of the proofreading mainly took the previously-proofread books as references,and widely referenced to the other editions of Wai Tai Mi Yao Fang,which reflected the proofreading principles of the Bureau of Revising Medical Books in Northern Song Dynasty,i.e.,collecting various editions widely and then identifying similarities and differences;(2)the analysis of the collation record in Zhongjing's Treatise on Exogenous Febrile Disease by using comparative proofreading method plus reasoning proofreading method showed that,the medical knowledge of the ministers of Song Dynasty had some limitations;(3)some of the medical terminology used by the ministers of Song Dynasty in their collation record influenced the naming convention of later generations of medical science,for example,making the Piyue Pills be the synonym of the Maziren Wan(Maren Wan).The results indicated that the complexity and uncertainty of the textual content of the popular edition of Wai Tai Mi Yao Fang should deserve the attention,and their influences on the development of later generations'scholarship need further in-depth study.

Objective:To explore the effect of necroptosis inhibitor necrosulfonamide (NSA) on traumatic brain injury (TBI) mouse model and BV2 cell pyroptosis model and their mechanisms.Methods:(1) In vivo experiments: 50 mice were randomly divided into sham-operated group, TBI group, TBI+1 mg/kg NSA group, TBI+5 mg/kg NSA group, and TBI+10 mg/kg NSA group, with 10 mice in each group. TBI model was established using a modified Feeney's weight-drop method; 4 h after modeling, 90% corn oil, 1 mg/kg NSA, 5 mg/kg NSA, or 10 mg/kg NSA was administered into the mice, respectively. Mice in the sham-operated group only had circular bone window opened without being subjected to impact. At 48 hours after modeling, neurological function was evaluated by modified neurological function score (mNSS), serum lactate dehydrogenase (LDH) content was detected by LDH detection kit, contents of interleukin (IL)-18, IL-1β and tumor necrosis factor-α (TNF-α) in the brain tissues were detected by enzyme-linked immunosorbent assay (ELISA), and expressions and localizations of ionized calcium binding adaptor molecule 1 (IBA-1), cysteinyl aspartate specific proteinase-1 (Caspase-1) p20 and gasdermin D (GSDMD) in the injured parietal cortex were detected by double immunofluorescent staining. (2) In vitro experiments: BV2 cells were divided into control group, lipopolysaccharide (LPS)+adenosine triphosphate (ATP)+dimethyl sulfoxide (DMSO) group, LPS+ATP+5 μmol/L NSA group, LPS+ATP+10 μmol/L NSA group, and LPS+ATP+15 μmol/L NSA group. Cells in the latter 4 groups were induced by LPS+ATP to establish BV2 cell pyroptosis model, and incubated with 2 μL DMSO, 5 μmol/L NSA, 10 μmol/L NSA, and 15 μmol/L NSA for 1 hour, respectively; cells in the control group were cultured conventionally. Contents of LDH, IL-1β, IL-18, and TNF-α in the cell culture supernatant were detected by ELISA; pyroptosis was detected by calcein acetoxymethyl ester (CAM)/propidium iodide (PI) double staining; protein expressions of nucleotide binding domain-like receptor protein 3 (NLRP3), Caspase-1 p20, GSDMD, and N-terminal fragment of GSDMD (GSDMD-N) were detected by Western blotting. Results:(1) Compared with the TBI group, the TBI+1 mg/kg NSA group, TBI+5 mg/kg NSA group and TBI+10 mg/kg NSA group had decreased mNSS score and serum LDH content, decreased IL-1β and IL-18 contents in the brain tissues and number of Caspase-1 p20 + cells in the injured parietal cortex, successively, with significant differences ( P<0.05). Compared with the TBI group ([287.80±12.26] cells/mm 2), the TBI+1 mg/kg NSA group, TBI+5 mg/kg NSA group, and TBI+10 mg/kg NSA group had decreased number of Iba-1 +GSDMD + cells in the injured parietal cortex ([213.70±11.87] cells/mm 2, [205.30±9.15] cells/mm 2, [131.70±13.69] cells/mm 2),successively, with significant differences ( P<0.05). Compared with the TBI group, the TBI+5 mg/kg NSA group and TBI+10 mg/kg NSA group had significantly decreased number of Iba-1 + cells in the injured parietal cortex, and the TBI+10 mg/kg NSA group had significantly decreased TNF-α content in the brain tissues and number of GSDMD + cells in the injured parietal cortex ( P<0.05). Compared with the TBI group ([247.20±9.88] cells/mm 2), the TBI+10 mg/kg NSA group had significantly decreased number of Iba-1 +Caspase-1 p20 + cells in the injured parietal cortex ([181.70±9.37] cells/mm 2, P<0.05). (2) Compared with the LPS+ATP+DMSO group, the LPS+ATP+5 μmol/L NSA group, LPS+ATP+10 μmol/L NSA group, and LPS+ATP+15 μmol/L NSA group had decreased IL-18 content in the supernatant, successively, with significant differences ( P<0.05); and compared with the LPS+ATP+DMSO group, the LPS+ATP+10 μmol/L NSA group and LPS+ATP+15 μmol/L NSA group had significantly decreased contents of LDH, IL-1β, and TNF-α in the supernatant and ratio of PI +/CAM + cell counts ( P<0.05). Compared with the LPS+ATP+DMSO group (2.62±0.50), the LPS+ATP+10 μmol/L NSA group and LPS+ATP+15 μmol/L NSA group had significantly decreased Caspase-1 p20 protein expression (1.36±0.14, 1.32±0.07, P<0.05). Compared with the LPS+ATP+DMSO group (5.00±1.67), the LPS+ATP+5 μmol/L NSA group and LPS+ATP+15 μmol/L NSA group had significantly decreased GSDMD protein expression (1.42±0.26, 1.68±0.32, P<0.05). Compared with the LPS+ATP+DMSO group (2.28±0.24), the LPS+ATP+15 μmol/L NSA group had significantly decreased GSDMD-N protein expression (1.23±0.08, P<0.05). Conclusion:NSA can inhibit microglial pyroptosis after TBI by inhibiting the Caspase-1 p20/GSDMD pathway, thereby playing a neuroprotective role.

Objective:To explore the effect of necroptosis inhibitor necrosulfonamide (NSA) on traumatic brain injury (TBI) mouse model and BV2 cell pyroptosis model and their mechanisms.Methods:(1) In vivo experiments: 50 mice were randomly divided into sham-operated group, TBI group, TBI+1 mg/kg NSA group, TBI+5 mg/kg NSA group, and TBI+10 mg/kg NSA group, with 10 mice in each group. TBI model was established using a modified Feeney's weight-drop method; 4 h after modeling, 90% corn oil, 1 mg/kg NSA, 5 mg/kg NSA, or 10 mg/kg NSA was administered into the mice, respectively. Mice in the sham-operated group only had circular bone window opened without being subjected to impact. At 48 hours after modeling, neurological function was evaluated by modified neurological function score (mNSS), serum lactate dehydrogenase (LDH) content was detected by LDH detection kit, contents of interleukin (IL)-18, IL-1β and tumor necrosis factor-α (TNF-α) in the brain tissues were detected by enzyme-linked immunosorbent assay (ELISA), and expressions and localizations of ionized calcium binding adaptor molecule 1 (IBA-1), cysteinyl aspartate specific proteinase-1 (Caspase-1) p20 and gasdermin D (GSDMD) in the injured parietal cortex were detected by double immunofluorescent staining. (2) In vitro experiments: BV2 cells were divided into control group, lipopolysaccharide (LPS)+adenosine triphosphate (ATP)+dimethyl sulfoxide (DMSO) group, LPS+ATP+5 μmol/L NSA group, LPS+ATP+10 μmol/L NSA group, and LPS+ATP+15 μmol/L NSA group. Cells in the latter 4 groups were induced by LPS+ATP to establish BV2 cell pyroptosis model, and incubated with 2 μL DMSO, 5 μmol/L NSA, 10 μmol/L NSA, and 15 μmol/L NSA for 1 hour, respectively; cells in the control group were cultured conventionally. Contents of LDH, IL-1β, IL-18, and TNF-α in the cell culture supernatant were detected by ELISA; pyroptosis was detected by calcein acetoxymethyl ester (CAM)/propidium iodide (PI) double staining; protein expressions of nucleotide binding domain-like receptor protein 3 (NLRP3), Caspase-1 p20, GSDMD, and N-terminal fragment of GSDMD (GSDMD-N) were detected by Western blotting. Results:(1) Compared with the TBI group, the TBI+1 mg/kg NSA group, TBI+5 mg/kg NSA group and TBI+10 mg/kg NSA group had decreased mNSS score and serum LDH content, decreased IL-1β and IL-18 contents in the brain tissues and number of Caspase-1 p20 + cells in the injured parietal cortex, successively, with significant differences ( P<0.05). Compared with the TBI group ([287.80±12.26] cells/mm 2), the TBI+1 mg/kg NSA group, TBI+5 mg/kg NSA group, and TBI+10 mg/kg NSA group had decreased number of Iba-1 +GSDMD + cells in the injured parietal cortex ([213.70±11.87] cells/mm 2, [205.30±9.15] cells/mm 2, [131.70±13.69] cells/mm 2),successively, with significant differences ( P<0.05). Compared with the TBI group, the TBI+5 mg/kg NSA group and TBI+10 mg/kg NSA group had significantly decreased number of Iba-1 + cells in the injured parietal cortex, and the TBI+10 mg/kg NSA group had significantly decreased TNF-α content in the brain tissues and number of GSDMD + cells in the injured parietal cortex ( P<0.05). Compared with the TBI group ([247.20±9.88] cells/mm 2), the TBI+10 mg/kg NSA group had significantly decreased number of Iba-1 +Caspase-1 p20 + cells in the injured parietal cortex ([181.70±9.37] cells/mm 2, P<0.05). (2) Compared with the LPS+ATP+DMSO group, the LPS+ATP+5 μmol/L NSA group, LPS+ATP+10 μmol/L NSA group, and LPS+ATP+15 μmol/L NSA group had decreased IL-18 content in the supernatant, successively, with significant differences ( P<0.05); and compared with the LPS+ATP+DMSO group, the LPS+ATP+10 μmol/L NSA group and LPS+ATP+15 μmol/L NSA group had significantly decreased contents of LDH, IL-1β, and TNF-α in the supernatant and ratio of PI +/CAM + cell counts ( P<0.05). Compared with the LPS+ATP+DMSO group (2.62±0.50), the LPS+ATP+10 μmol/L NSA group and LPS+ATP+15 μmol/L NSA group had significantly decreased Caspase-1 p20 protein expression (1.36±0.14, 1.32±0.07, P<0.05). Compared with the LPS+ATP+DMSO group (5.00±1.67), the LPS+ATP+5 μmol/L NSA group and LPS+ATP+15 μmol/L NSA group had significantly decreased GSDMD protein expression (1.42±0.26, 1.68±0.32, P<0.05). Compared with the LPS+ATP+DMSO group (2.28±0.24), the LPS+ATP+15 μmol/L NSA group had significantly decreased GSDMD-N protein expression (1.23±0.08, P<0.05). Conclusion:NSA can inhibit microglial pyroptosis after TBI by inhibiting the Caspase-1 p20/GSDMD pathway, thereby playing a neuroprotective role.

The diagnostic technology of acute stroke by microwave imaging has the advantages of being non-ionizing, fast, small, and low-cost. Therefore, this technology is expected to become an auxiliary or alternative means to CT and MRI technology. As the signal transmitting and receiving device of the microwave imaging system, the antenna has an important influence on the performance of the imaging system. At present, there are many antennas with different performances used in imaging systems, but there is a lack of clear evaluation criteria for them. In this paper, several typical antennas were introduced, their advantages and disadvantages from the perspective of bandwidth and near-field were analyzed, and the common requirements of imaging systems for antennas and the performance indicators of various types of imaging systems were summarized. Moreover, the development trend of antenna technology for microwave imaging was pointed out to provide a reference for the study of stroke microwave imaging technology.

BACKGROUNDAdvances in transplantation immunology show that the balance between dendritic cells (DCs) and their subsets can maintain stable immune status in the induction of tolerance after transplantation. The aim of this study was to investigate if DCs and DC subpopulations in recipient peripheral blood are effective diagnostic indicators of acute rejection following kidney transplantation.

METHODSImmunofluorescent flow cytometry was used to classify white blood cells (WBCs), the levels of mononuclear cells and DCs (including the dominant subpopulations, plasmacytoid DC (pDC) and myeloid DC (mDC)) in peripheral blood at 0, 1, 7, and 28 days and 1 year after kidney transplantation in 33 patients. In addition, the blood levels of interleukin-10 (IL-10) and IL-12 were monitored before and after surgery. Fifteen healthy volunteers served as normal controls. Patients were undertaking hemodialysis owing to uremia before surgery.

RESULTSThe total number of DCs, pDC, and mDC in peripheral blood and the pDC/mDC ratio were significantly lower in patients than controls (P < 0.05). Peripheral DCs suddenly decreased at the end of day 1, then gradually increased through day 28 but remained below normal levels. After 1 year, levels were higher than before surgery but lower than normal. The mDC levels were higher in patients with acute rejection before and 1 day after surgery (P < 0.005). There was no significant difference in IL-10 and IL-12 levels between patients with and without acute rejection.

CONCLUSIONThe changes in DCs and DC subpopulations during the acute rejection period may serve as effective markers and referral indices for monitoring the immune state, and predicting rejection and reasonably adjusting immunosuppressants.

Adolescent ; Adult ; Dendritic Cells ; immunology ; Graft Rejection ; immunology ; Humans ; Kidney Transplantation ; adverse effects ; Middle Aged ; Myeloid Cells ; immunology ; Young Adult

Objective To evaluate the role of autophagy in the development of neuropathic pain (NP) in rats.Methods Thirty male Sprague-Dawley rats,weighing 200-220 g,were randomly divided into 3 groups (n =10 each) using a random number table:sham operation group (sham group),NP group and rapamycin (autophagy inducer) group (Rap group).Intrathecal catheter was inserted into the subarachnoid space and advanced caudally until the tip reached L4,5 segment.NP was induced by ligation of the left L5 spinal nerve (SNL) in NP and Rap groups.The L5 spinal nerve was only exposed,but not ligated in group sham.At 30 min before ligation and 2 days after operation,rapamycin 60 μg was injected intrathecally via the intrathecal catheter in Rap group,while the equal volume of vehicle (5％ dimethyl sulfoxide) was injected in sham and NP groups.The mechanical and thermal pain thresholds were measured on 1,3,5 and 7 days after ligation (T-4).The rats were sacrificed after the last measurement of pain threshold at T4.The ipsilateral L5 segment of spinal dorsal horn was removed for examination of autophagosomes (using transmission electron microscope) and for determination of the expression of LC3 Ⅱ and p62 (by Western blot) and content of IL-1β (by ELISA).Results Compared with sham group,the mechanical pain threshold at each time point and thermal pain threshold at T2-4 were significantly decreased,and the LC3 Ⅱ and p62 expression and IL-1β content were increased at T4 in group NP (P ＜ 0.05).Compared with NP group,the mechanical pain threshold at each time point,thermal pain threshold at T2-4 and LC3 Ⅱ expression at T4 were significantly increased,and the p62 expression and IL-1β content were decreased at T4 in group Rap (P ＜ 0.05).Microscopic examination showed that autophagosomes were observed in the spinal dorsal horn in NP and Rap groups,and the damage to organelles was lighter in Rap group than in NP group.Conclusion The development of NP is related to autophagic dysfunction in rats.

Objective To analyze the dynamic changes of dendritic ceils (DCs) and their subsets plasmacytoid DC (pDC) and myeliod DC (mDC) in peripheral blood of renal transplantation patients,and to confer the relationship between DCs subsets and graft rejection.Methods White blood cells (WBC) and mononuclear cells (PBMNCs) in peripheral blood of 28 renal transplantation recipients (test group) were measured before operation and at 1st,7th,28th day after operation.The number of DCs and subsets,and pDC/mDC were detected by using flow cytometry,and IL-10 and IL-12 levels were determined by using ELISA before and after operation.Ten volunteers (control group) served as controls.Results The levels of DCs,pDC and mDC before operation in test group were lower than in control group (P＜0.05),but there was no statistically significant difference in pDC/mDC ratio between two groups (P＞0.05).The number of DCs in test group was significantly decreased on the first day after operation up to the lowest level,then slowly increased,and recovered 73.7 ％ at 28th day after operation.The number of mDC and pDC was also decreased after operation,but mDC recovered faster than pDC (P＜0.05).On the day 7th after operation,the number of mDC in the recipients with graft rejection was higher than in those without graft rejection in test group (P＜0.01 ).There was no significant difference before and after operation in the levels of IL-10 and IL-12 in test group.Conclusion The number of DCs and subsets are related to the recipients' immune state,and their abnormality displays unstable immune state of recipients.The number of DCs and subsets can be used as an assistance index to diagnose graft rejection.