OBJECTIVE To form an expert consensus addressing clinical issues regarding the use of parenteral direct thrombin inhibitors （DTIs） in special populations. METHODS Led by the Sichuan Academy of Medical Sciences & Sichuan Provincial People’s Hospital（the Affiliated Hospital of UESTC）， a multidisciplinary working group was formed comprising experts from multiple fields， including clinical pharmacy， cardiac surgery， obstetrics， pediatrics and evidence-based medicine. Through literature review and the Delphi method， clinical questions regarding the efficacy and safety of parenteral DTIs used in special populations were identified. A structured design was adopted using the “Population-Intervention-Comparison-Outcome” （PICO） framework；systematic searches were conducted in CJFD， PubMed， Embase and other databases. Relevant evidence from randomized controlled trials，cohort studies and systematic reviews were included and synthesized. Evidence quality was assessed using the Grading of Recommendations Assessment，Development and Evaluation （GRADE） approach， and recommendations were formulated through three rounds of Delphi surveys and expert consensus meetings. RESULTS &CONCLUSIONS Seven clinical questions were ultimately selected （with a consensus rate exceeding 90%）， resulting in the formulation of seven recommendations on the use of parenteral DTIs in special populations， including children， pregnant women， patients with hepatic or renal impairment， patients with mesenteric venous thrombosis， and individuals with thrombophilia. These recommendations clarify the preferred agents， dosing ranges， monitoring parameters， and safety management strategies for parenteral DTIs in these special populations. This expert consensus， which is formulated based on the best available evidence， provides evidence-based guidance for standardized and individualized use of parenteral DTIs in special populations.

ObjectiveTo explore the potential mechanism of Xiezhuo Jiedu prescription in regulating autophagy in the treatment of ulcerative colitis （UC） by bioinformatics and animal experiments. MethodsThe differentially expressed genes （DEGs） in the colonic mucosal tissue of UC patients was obtained from the Gene Expression Omnibus （GEO）， and those overlapped with autophagy genes were obtained as the differentially expressed autophagy-related genes （DEARGs）. DEARGs were imported into Metascape and STRING， respectively， for gene ontology/Kyoto Encyclopedia of Genes and Genomics （GO/KEGG） enrichment analysis and protein-protein interaction （PPI） analysis. Finally， 15 key DEARGs were obtained. The core DEARGs were obtained by least absolute shrinkage and selection operator （LASSO） regression and receiver operating characteristic curve （ROC） analysis. The CIBERSORT deconvolution algorithm was used to analyze the immunoinfiltration of UC patients and the correlations between core DEARGs and immune cells. C57BL/6J mice were assigned into a normal group and a modeling group. The mouse model of UC was established by free drinking of 2.5% dextran sulfate sodium. The modeled mice were assigned into low-， medium-， and high-dose Xiezhuo Jiedu prescription and mesalazine groups according to the random number table method and administrated with corresponding agents by gavage for 7 days. The colonic mucosal morphology was observed by hematoxylin-eosin staining. The protein and mRNA levels of cysteinyl aspartate-specific proteinase 1 （Caspase-1）， cathepsin B （CTSB）， C-C motif chemokine-2 （CCL2）， CXC motif receptor 4 （CXCR4）， and hypoxia-inducing factor-1α （HIF-1α） in the colon tissue were determined by Western blot and real-time fluorescence quantitative polymerase chain reaction， respectively. ResultsThe dataset GSE87466 was screened from GEO and interlaced with autophagy genes. After PPI analysis， LASSO regression， and ROC analysis， the core DEARGs （Caspase-1， CCL2， CTSB， and CXCR4） were obtained. The results of immunoinfiltration analysis showed that the counts of NK cells， M0 macrophages， M1 macrophages， and dendritic cells in the colonic mucosal tissue of UC patients had significant differences， and core DEARGs had significant correlations with these immune cells. This result， combined with the prediction results of network pharmacology， suggested that the HIF-1α signaling pathway may play a key role in the regulation of UC by Xiezhuo Jiedu prescription. The animal experiments showed that Xiezhuo Jiedu prescription significantly alleviated colonic mucosal inflammation in UC mice. Compared with the normal group， the model group showed up-regulated protein and mRNA levels of caspase-1， CCL2， CTSB， CXCR4， and HIF-1α， which were down-regulated after treatment with Xiezhuo Jiedu prescription or mesalazine. ConclusionCaspase-1， CCL2， CTSB， and CXCR4 are autophagy genes that are closely related to the onset of UC. Xiezhuo Jiedu prescription can down-regulate the expression of core autophagy genes to alleviate the inflammation in the colonic mucosa of mice.

Objective To investigate the therapeutic efficacy of artesunate(AS)on polycystic ovary syndrome(PCOS)in mice and explore the potential mechanism primarily.Methods Twenty-five female C57BL/6J mice were randomly divided into Control group,model group(PCOS group),low-and high-dose AS groups(AS15 and AS30 groups)and metformin group(Met group).In addition to the Control group,the mouse model of PCOS was established by subcutaneous injection of dehydroepiandrosterone(DHEA,60 mg/kg)following by a high-fat diet for 21 d.After modeling,AS of 15 and 30 mg/kg was intraperitoneally injected into the mice of the AS 15 and AS30 groups,respectively,and 200 mg/kg Met was given to those of the Met group by gavage,once per day,for 6 weeks.ELISA was used to detect serum testosterone(T),fasting insulin(FINS),luteinizing hormone(LH)and follicle-stimulating hormone(FSH),and the LH/FSH ratio was calculated.The levels of fasting blood glucose(FBG),triglyceride(TG)and total cholesterol(TC)were detected by automatic biochemical analyzer,and the homeostasis model assessment of insulin resistance(HOMA-IR)was calculated.The estrous cycle was observed,and HE staining was performed for pathological changes in the ovary and uterus.Immunofluorescence assay was employed to measure the expression of p-eIF2α,ATF4 and CHOP in the ovarian tissue.After steroidogenic human granulosa-like tumor cell line KGN were exposed to 100 μmol/L DHEA to simulate the hyperandrogen environment of PCOS,and then treated with 5 and 10 μg/mL AS for 24 h,the protein levels of endoplasmic reticulum stress signaling pathway was detected by Western blotting.Results Compared with the Control group,the PCOS mice had disturbed estrous cycle,polycystic changes in the ovaries,and significantly increased serum T level and LH/FSH ratio(P＜0.05),and obviously elevated HOMA-IR,TC and TG levels in terms of metabolism(P＜0.01).The expression levels of p-eIF2α,ATF4 and CHOP were notably up-regulated in the ovarian granulosa cells of PCOS mice and KGN cells after DHEA exposure(P＜0.05).Additionally,AS treatment attenuated the pathological changes of ovary and uterine expression,decreased the serum T level and the LH/FSH ratio(P＜0.05),and reduced HOMA-IR,TC and TG levels(P＜0.05)when compared with the PCOS mice.Moreover,the expression levels of p-eIF2α,ATF4 and CHOP were significantly down-regulated after AS treatment in both ovarian granulosa cells of PCOS mice and KGN cells(P＜0.05).Conclusion AS significantly improves glycolipid metabolic disorder and reproductive dysfunction in PCOS mice,which may be associated with its suppressing endoplasmic reticulum stress by inhibiting the PERK/eIF2α/ATF4/CHOP pathway.

Instrument separation is a critical complication during root canal therapy, impacting treatment success and long-term tooth preservation. The etiology of instrument separation is multifactorial, involving the intricate anatomy of the root canal system, instrument-related factors, and instrumentation techniques. Instrument separation can hinder thorough cleaning, shaping, and obturation of the root canal, posing challenges to successful treatment outcomes. Although retrieval of separated instrument is often feasible, it carries risks including perforation, excessive removal of tooth structure and root fractures. Effective management of separated instruments requires a comprehensive understanding of the contributing factors, meticulous preoperative assessment, and precise evaluation of the retrieval difficulty. The application of appropriate retrieval techniques is essential to minimize complications and optimize clinical outcomes. The current manuscript provides a framework for understanding the causes, risk factors, and clinical management principles of instrument separation. By integrating effective strategies, endodontists can enhance decision-making, improve endodontic treatment success and ensure the preservation of natural dentition.
Humans ; Root Canal Therapy/adverse effects* ; Consensus ; Root Canal Preparation/adverse effects*

Glutamine provides carbon and nitrogen to support the proliferation of cancer cells. However, the precise reason why cancer cells are particularly dependent on glutamine remains unclear. In this study, we report that glutamine modulates the tumor suppressor F-box and WD repeat domain-containing 7 (FBW7) to promote cancer cell proliferation and survival. Specifically, lysine 604 (K604) in the sixth of the 7 substrate-recruiting WD repeats of FBW7 undergoes glutaminylation (Gln-K604) by glutaminyl tRNA synthetase. Gln-K604 inhibits SCFFBW7-mediated degradation of c-Myc and Mcl-1, enhances glutamine utilization, and stimulates nucleotide and DNA biosynthesis through the activation of c-Myc. Additionally, Gln-K604 promotes resistance to apoptosis by activating Mcl-1. In contrast, SIRT1 deglutaminylates Gln-K604, thereby reversing its effects. Cancer cells lacking Gln-K604 exhibit overexpression of c-Myc and Mcl-1 and display resistance to chemotherapy-induced apoptosis. Silencing both c-MYC and MCL-1 in these cells sensitizes them to chemotherapy. These findings indicate that the glutamine-mediated signal via Gln-K604 is a key driver of cancer progression and suggest potential strategies for targeted cancer therapies based on varying Gln-K604 status.
Glutamine/metabolism* ; Myeloid Cell Leukemia Sequence 1 Protein/genetics* ; Humans ; Proto-Oncogene Proteins c-myc/genetics* ; Cell Proliferation ; Signal Transduction ; Neoplasms/pathology* ; F-Box-WD Repeat-Containing Protein 7/genetics* ; Cell Survival ; Cell Line, Tumor ; Apoptosis

Objective:To investigate the effects of intravenous lidocaine infusion (IVLI) on the quality of intraoperative neurophysiologic monitoring (IONM) in patients with thyroid tumor.Methods:A prospective randomized controlled study was conducted. A total of 60 patients with thyroid tumor undergoing thyroidectomy in the First Clinical Medical College of Shanxi Medical University between September 2022 and May 2023 were selected. According to the random number table method, all patients were divided into the lidocaine group and the control group, 30 cases in each group. The patients in the lidocaine group were continually given IVLI during the operation and the patients in the control group were continually given the equal 0.9% NaCl solution infusion during the operation. All patients in the 2 groups were induced by the same way of total intravenous anesthesia, and no muscle relaxants were added during anesthesia except the induction dose, and enhanced nerve monitoring tracheal catheter was inserted in the 2 groups. According to the standardized procedure of IONM, the electrode impedance values were measured at the time of eliciting the V1 and V2 signals from the vagus nerve, respectively, and the difference value was defined as the drop in the aggregate impedance level (DAIL). DAIL, perioperative hemodynamic parameters and postoperative recovery quality were compared between the 2 groups.Results:There were no statistically significant differences in the baseline data, operation time, intraoperative dosage of propofol and remifentanil between the 2 groups (all P > 0.05). Compared with the control group, the lidocaine group had a higher proportion of patients with DAIL<50% [80.0% (24/30) vs. 40.0% (12/30), χ2 = 10.00, P = 0.002], a lower hemodynamic fluctuation during extubation [mean arterial pressure: (95±6) mmHg (1 mmHg = 0.133 kPa) vs. (104±7) mmHg, t = 31.00, P < 0.001; heart rate: (73±5) times/min vs. (92±6) times/min, t = 172.58, P < 0.001], a lower visual analog score 24 h after surgery [(2.0±0.7) scores vs. (3.7±0.8) scores, t = -8.86, P < 0.001], a higher score of quality of recovery-15 scale [(127±11) points vs. (118±13) points, t = 2.92, P = 0.005]. Conclusions:IVIL can improve the quality of IONM in patients with thyroid tumor during surgery, reduce perioperative hemodynamic fluctuation and improve postoperative recovery quality of patients.

Objective To investigate the radiological features of intracranial white epidermoid cysts(WECs).Methods A retro-spective analysis was conducted on the CT and MRI findings of 7 patients pathologically confirmed with WECs.All patients under-went plain CT and MRI scans,and six patients underwent enhanced MRI scans.Results All cases were solitary lesions,located in the right middle cranial fossa(2 cases),suprasellar area(2 cases),left cerebellopontine angle(1 case),right cerebellar vermis(1 case),and cerebellomedullary cistern(1 case),respectively.The lesions appeared oval or irregular in shape with clear boundaries and no perile-sional edema.The CT scans predominantly showed high density in 7 cases,with calcification in 1 case.On T1WI,7 cases exhibited high signal with mixed signals in some areas;6 cases showed primarily low signal on T2WI and fluid attenuated inversion recovery(FLAIR),with 1 case predominantly showed high signal;all 7 cases demonstrated low signal on diffusion weighted imaging(DWI).The margins of 1 lesion appeared"curly",and another exhibited a"swirl"pattern.5 cases had no enhancement,while 1 case had mild marginal enhancement.Conclusion Intracranial WECs has certain imaging characteristics.When a cystic lesion shows high density on CT,predominantly high signal on T1WI,and mostly no enhancement,considering the possibility of WECs.

Objective:This study aimed to evaluate the effects of hypertensive disorders of pregnancy (HDP), including their clinical subtypes, on neonatal heel blood methionine levels and explore potential dose-effect relationships.Methods:A retrospective cohort study was conducted among 11 007 singleton pregnancies and their neonates delivered at Beijing Obstetrics and Gynecology Hospital, Capital Medical University, from July 2021 to October 2022. Participants were stratified into an HDP group [ n=992; 480 with gestational hypertension, 512 with preeclampsia (including 229 severe cases)] and a non-HDP control group ( n=10 015). Methionine concentrations were measured using tandem mass spectrometry from heel blood dried filter paper samples collected within 72 hours post-delivery. Statistical analyses included non-parametric tests to compare intergroup differences, multiple linear regression to evaluate the effects of HDP on methionine levels, and multivariate logistic regression to identify risk factors for hypermethioninemia (>50 μmol/L). Results:(1) Baseline data: Maternal age was higher in the HDP group compared to controls [33 (30-36) vs. 33 (30-35) years, Z=－2.29, P=0.022], with elevated pre-pregnancy body mass index (BMI) [23 (21-26) vs. 21 (20-23) kg/m2, Z=－17.15, P<0.001] and increased gestational hyperglycemia prevalence [26.5% (263/992) vs. 19.8% (1 986/10 015), χ2=27.95, P<0.001]. (2) Methionine level: Neonates in the HDP group exhibited higher methionine levels [25.96 (21.58-30.89) vs. 24.77 (20.45-29.53) μmol/L, Z=－5.26, P<0.001], with a severity-dependent gradient: gestational hypertension [25.83 (21.77-30.61)], preeclampsia [26.05 (21.23-31.11)], and severe preeclampsia [26.15 (21.25-32.13)] ( Z=2.97, 3.92, 2.26; all P<0.05). Trend analysis confirmed a dose-effect relationship between HDP and neonatal methionine ( χ2=7.82, P=0.005). (3) Multivariate analysis: After adjusting for confounding factors such as maternal age and BMI, HDP remained independently associated with elevated methionine levels ( β=0.93, 95% CI: 0.47-1.40, t=3.92, P<0.001) and increased hypermethioninemia risk ( OR=2.75, 95% CI: 1.13-6.68). Subgroup analysis revealed ORs of 3.20 (95% CI: 1.07-9.57) for gestational hypertension, 3.25 (95% CI: 1.09-9.72) for preeclampsia, and 5.23 (95% CI: 1.54-17.82) for severe preeclampsia (all P<0.05). (4) Neonatal outcomes: Neonates in the HDP group had lower birth weights [3 230 (2 910-3 560) vs. 3 335 (3 070-3 600) g, Z=－7.43, P<0.001] and higher fetal growth restriction rates [10.3% (102/992) vs. 3.1% (306/10 015), χ2=136.47, P<0.001]. Conclusions:HDP demonstrates an elevation of neonatal methionine levels, correlating with disease severity, particularly in severe preeclampsia. These findings underscore the necessity for enhanced metabolic monitoring and long-term follow-up in offspring of mothers with HDP, especially those with severe preeclampsia.

Soy is a vital source of plant carbohydrates.However,it poses significant allergenic risks,particularly to young children and animals.Among the various proteins in soy,β-conglycinin,which con-stitutes approximately 30％of total soy carbohydrates,is a primary allergen.Undigested β-conglycinin can lead to intestinal damage by inhibiting cell growth,disrupting the cytoskeleton,and inducing apopto-sis.It can also enter the lymphatic and circulatory systems,triggering allergic reactions.Conventional ELISA methods for detecting β-conglycinin rely on polyclonal or monoclonal antibodies,which are limited by their large molecular weight,difficulty in accessing the protein core,and sensitivity to acidic and bas-ic conditions.To address these limitations,this study aimed to develop nanobodies(Nbs)against β-con-glycinin.Nbs,derived from the variable regions of heavy-chain antibodies found in camelids,have a mo-lecular weight approximately one-tenth that of conventional antibodies.They offer advantages such as small size,stable structure,high specificity,and strong affinity.A female alpacas was immunized five times using β-conglycinin,which showed a heavy chain antibody potency of 1∶16 000 by ELISA.Pe-ripheral blood lymphocytes were subsequently isolated and total RNA was extracted.The variable region of the heavy-chain antibody was amplified via PCR,and recombinant plasmids were constructed and transformed into the E.coli competency strain ER2738.The resulting library contained about 3.5×108 CFU/mL,which increased to 1.15×1012 PFU/mL after phage rescue,with a 100％Nbs gene insertion rate,indicating high diversity.Its Nbs phage output was significantly enriched by four rounds of solid-phase elution with an enrichment rate of 155.9.Four rounds of solid-phase panning yielded 35 positive clones,all of which shared the same amino acid sequence upon sequencing.The selected Nb was ex-pressed in a prokaryotic system,and its binding ability to β-conglycinin was confirmed using Western blotting and ELISA.The results demonstrated excellent specificity and affinity.This research lays the groundwork for developing a rapid and efficient detection method for β-conglycinin using Nbs,potentially enhancing food safety and allergen management.

Objective:To evaluate the feasibility of transjugular transcatheter tricuspid valve replacement (TTVR) using the LuX-Valve Plus system (Ningbo Jenscare Scientific, China) for the treatment of severe tricuspid regurgitation in real-world clinical settings.Methods:This prospective study enrolled 81 patients with severe ricuspid regurgitation (≥3+) who underwent TTVR with the LuX-Valve Plus system at the Department of Cardiology, West China Hospital of Sichuan University between May 2022 and March 2024. Among them, 44 patients were from a compassionate-use study, and 37 were from two premarket clinical trials. Baseline clinical data, preprocedural imaging, procedural outcomes, and postprocedural follow-up data were collected. The primary endpoint events included device success, procedural success, and 30 d composite adverse events.Results:The age of the cohort was (74.5±7.8) years, with 54 females (67%). Device success and procedural success rates were both 90% (73/81). Post-procedural tricuspid regurgitation improved, with a 6% (5/81) incidence of moderate-to-severe paravalvular leakage. The rate of permanent pacemaker implantation was 12% (10/81), of which 5% (4/81) had pre-existing indications for pacemaker implantation. Major bleeding events occurred in 10% (8/81) of patients, and the 30 d composite endpoint rate was 25% (20/81).Conclusion:TTVR using the LuX-Valve Plus system demonstrates promising feasibility for high-risk surgical patients with severe tricuspid regurgitation, effectively reducing or eliminating regurgitation with acceptable safety. However, challenges remain in reducing risks of major adverse events, including permanent pacemaker implantation and severe bleeding.