Objective:To compare the efficacy of anrikefon and tegileridine for analgesia in patients with moderate-to-severe pain after abdominal surgery with general anesthesia.Methods:In this multicenter, randomized, double-blind, active-controlled clinical trial, 101 patients with moderate to severe pain (numeric pain rating scale [NRS] score ≥4 within 4 h after operation) after abdominal surgery with general anesthesia between February 24 and April 1, 2025, aged 18-70 yr, with a body mass index of 18-40 kg/m 2, were assigned to anrikefon group ( n=50) and tegileridine group ( n=51) in a 1∶1 ratio using stratified blocked randomization. Double-dummy design was employed to maintain blinding. Each group received an initial intravenous injection of anrikefon 1 μg/kg or tegileridine 1 mg, followed by connection to a patient-controlled intravenous analgesia (PCIA) pump (the PCIA solution contained normal saline in anrikefon group; the PCIA solution contained tegileridine 5 mg in tegileridine pump) within 10 min. If the patient′s NRS score ≥4 at 8 and 16 h after the initial injection, anrikefon 1 μg/kg was intravenously injected in anrikefon group, and tegileridine group received the equal volume of normal saline. The primary efficacy endpoint was the sum of pain intensity difference (SPID) over the first 24 h after the initial dose (SPID 0-24h). The secondary efficacy endpoints included the incidence and severity of vomiting and nausea, incidence of postoperative nausea and vomiting(PONV), the proportion of patients who received antiemetic treatment, and total consumption of antiemetics within 0-24 h after the initial dose, NRS score at rest ≤ 1 at 24 h after the initial dose, and NRS score at rest ≤ 3 over the first 24 h after the initial dose. Safety indicators included adverse events, vital signs, physical examination findings, 12-lead ECG and laboratory test indicators, and adverse events of special interest. Results:Compared with tegileridine group, no significant change was found in the SPID 0-24h ( P>0.05), and the incidence of vomiting, PONV, proportion of patients requiring antiemetic medication, and total consumption of antiemetics were significantly decreased within the first 24 h after the initial dose in tegileridine group ( P<0.05). One treatment-emergent adverse event of Common Terminology Criteria for Adverse Events grade 3 or higher occurred in tegileridine group, while no treatment-emergent adverse events of Common Terminology Criteria for Adverse Events grade 3 or higher were found in anrikefon group. Among the adverse events of special interest, one case of respiratory depression and one case of cough occurred in tegileridine group, while one case of cough occurred in anrikefon group, with no respiratory depression. Conclusions:Anrikefon and tegileridine provide comparable analgesic efficacy for moderate-to-severe pain after abdominal surgery with general anesthesia. However, anrikefon exhibits an advantage in reducing the risk of PONV, with a superior safety profile.

Objective:To compare the efficacy of anrikefon and tegileridine for analgesia in patients with moderate-to-severe pain after abdominal surgery with general anesthesia.Methods:In this multicenter, randomized, double-blind, active-controlled clinical trial, 101 patients with moderate to severe pain (numeric pain rating scale [NRS] score ≥4 within 4 h after operation) after abdominal surgery with general anesthesia between February 24 and April 1, 2025, aged 18-70 yr, with a body mass index of 18-40 kg/m 2, were assigned to anrikefon group ( n=50) and tegileridine group ( n=51) in a 1∶1 ratio using stratified blocked randomization. Double-dummy design was employed to maintain blinding. Each group received an initial intravenous injection of anrikefon 1 μg/kg or tegileridine 1 mg, followed by connection to a patient-controlled intravenous analgesia (PCIA) pump (the PCIA solution contained normal saline in anrikefon group; the PCIA solution contained tegileridine 5 mg in tegileridine pump) within 10 min. If the patient′s NRS score ≥4 at 8 and 16 h after the initial injection, anrikefon 1 μg/kg was intravenously injected in anrikefon group, and tegileridine group received the equal volume of normal saline. The primary efficacy endpoint was the sum of pain intensity difference (SPID) over the first 24 h after the initial dose (SPID 0-24h). The secondary efficacy endpoints included the incidence and severity of vomiting and nausea, incidence of postoperative nausea and vomiting(PONV), the proportion of patients who received antiemetic treatment, and total consumption of antiemetics within 0-24 h after the initial dose, NRS score at rest ≤ 1 at 24 h after the initial dose, and NRS score at rest ≤ 3 over the first 24 h after the initial dose. Safety indicators included adverse events, vital signs, physical examination findings, 12-lead ECG and laboratory test indicators, and adverse events of special interest. Results:Compared with tegileridine group, no significant change was found in the SPID 0-24h ( P>0.05), and the incidence of vomiting, PONV, proportion of patients requiring antiemetic medication, and total consumption of antiemetics were significantly decreased within the first 24 h after the initial dose in tegileridine group ( P<0.05). One treatment-emergent adverse event of Common Terminology Criteria for Adverse Events grade 3 or higher occurred in tegileridine group, while no treatment-emergent adverse events of Common Terminology Criteria for Adverse Events grade 3 or higher were found in anrikefon group. Among the adverse events of special interest, one case of respiratory depression and one case of cough occurred in tegileridine group, while one case of cough occurred in anrikefon group, with no respiratory depression. Conclusions:Anrikefon and tegileridine provide comparable analgesic efficacy for moderate-to-severe pain after abdominal surgery with general anesthesia. However, anrikefon exhibits an advantage in reducing the risk of PONV, with a superior safety profile.

Objective To investigate the effects of acute hypervolemic hemodilution(AHH)on coagulation function and visceral perfusion in elderly patients undergoing hip replacement.Methods A retrospective study was conducted on 102 elderly patients who underwent hip replacement in Jinhua Municipal Central Hospital from January 2021 to June 2023.All patients were treated with AHH,autologous blood transfusion and controlled hypotension,and were divided into group A(n=55)and group B(n=47)according to the degree of AHH.The target dilution value was 30％hematocrit(HCT)for group A and 25％HCT for group B.The general data,urine volume,total infusion volume,blood loss,and heart rate,body temperature,prothrombin time(PT),fibrinogen(FIB),activated partial thromboplastin time(APTT),platelet(PLT)and gastric intramucosal carbon dioxide tension(PgCO2),gastric intramucosal pH(pHi)after anesthesia induction(T0),hemodilution(T1)and postoperative(T2)were compared between two groups.Results The total amount of expanded liquid and infusion in group B was higher than that in group A(P＜0.05).The heart rate and body temperature of T1 in two groups were lower than those of T0 and T2,and heart rate of T1 in group B was lower than that in group A(P＜0.05).The PT of T1 and T2 was longer than that of T0,FIB and PLT were lower than those of T0(P＜0.05).PLT of T1 and T2 in group B was lower than that in group A(P＜0.05).PgCO2 of T1 and T2 in two groups was higher than that of T0,pHi was lower than that of T0(P＜0.05),and pHi of T,and T2 in group B was significantly lower than that in group A(P＜0.05).Conclusion The overall safety of AHH is high when the target value is 25％to 30％of HCT.When the target value is 25％of HCT,PLT level is lower,but it is also in the normal range,while PgCO2 is increased,pHi is decreased.

Gastrointestinal malignant tumors are common worldwide,particularly gastric cancer(GC)and colorectal cancer(CRC),with complex and not fully understood molecular mechanisms behind their occurrence and progression.Treatment typically involves a comprehensive approach centered on surgery,which,despite achieving good outcomes,still faces challenges due to high recurrence rates and low survival rates impacting patient health.N6-methyladenosine(m6A)is the most abundant internal modification in mRNAs and plays a crucial role in regulating RNA post-transcriptional modifications and downstream functions.Fat mass and obesity-associated protein(FTO)was the first identified m6A demethylase capable of removing dynamic,reversible m6A modifications.During the development of gastrointestinal malignancies,FTO regulates the expression of specific genes,affecting tumor cell proliferation and metastasis;modulates the expression of tumor-related cytokines and immune-related molecules,influencing the tumor microenvironment;and plays a significant role in sensitivity and resistance to chemotherapy.FTO is upregulated in most types of GC,indicating poor prognosis.High FTO expression enhances GC cell migration and invasion,increases chemoresistance,promotes tumor stem cell proliferation and differentiation,and inhibits apoptosis,thus facilitating GC progression.In CRC,many studies show that FTO is upregulated in tissues and cells,promoting CRC progression by enhancing cell proliferation,migration,invasion,and resistance to chemotherapy.Low FTO expression can also elevate m6Am levels in CRC cell cytoplasmic mRNA,promoting tumor stem cell proliferation,differentiation,tumor formation,and increasing resistance.In contrast,high FTO expression inhibits tumor stem cell proliferation and differentiation.FTO is also upregulated in other gastrointestinal tumors like pancreatic and esophageal cancers,where high expression promotes progression and indicates poor prognosis.FTO has both promoting and inhibitory effects on liver and biliary malignancies.As research confirms FTO's widespread oncogenic role in the gastrointestinal tract,developing FTO inhibitors and related drugs offers new avenues for treating gastrointestinal malignancies.Currently identified agents like CS1,omeprazole,and mupirocin significantly inhibit CRC and GC progression by directly or indirectly suppressing FTO.Tumors can evade immune surveillance through FTO-mediated mechanisms,suggesting that blocking FTO-mediated immune escape and enhancing the antitumor effects of immune cells could provide treatment options for gastrointestinal malignancies.Targeting FTO in combination with immunotherapy to inhibit GC and CRC growth and metastasis and reduce resistance presents broad therapeutic prospects.

The Ly-6 and uPAR (LU) domain-containing proteins represent a large family of cell-surface markers. In particular, mouse Ly-6A/Sca-1 is a widely used marker for various stem cells; however, its human ortholog is missing. In this study, based on a systematic survey and comparative genomic study of mouse and human LU domain-containing proteins, we identified a previously unannotated human gene encoding the candidate ortholog of mouse Ly-6A/Sca-1. This gene, hereby named LY6A, reversely overlaps with a lncRNA gene in the majority of exonic sequences. We found that LY6A is aberrantly expressed in pituitary tumors, but not in normal pituitary tissues, and may contribute to tumorigenesis. Similar to mouse Ly-6A/Sca-1, human LY6A is also upregulated by interferon, suggesting a conserved transcriptional regulatory mechanism between humans and mice. We cloned the full-length LY6A cDNA, whose encoded protein sequence, domain architecture, and exon-intron structures are all well conserved with mouse Ly-6A/Sca-1. Ectopic expression of the LY6A protein in cells demonstrates that it acts the same as mouse Ly-6A/Sca-1 in their processing and glycosylphosphatidylinositol anchoring to the cell membrane. Collectively, these studies unveil a novel human gene encoding a candidate biomarker and provide an interesting model gene for studying gene regulatory and evolutionary mechanisms.
Humans ; Membrane Proteins/genetics* ; Pituitary Neoplasms/genetics* ; Biomarkers

Objective:To compare the influence of single and staged percutaneous coronary intervention (PCI) on long-term prognosis in patients with multi-vessel coronary artery disease.Methods:Using prospective research methods, 1 832 patients with multi-vessel coronary artery disease from January to December 2013 in Fuwai Hospital, Chinese Academy of Medical Sciences were selected. According to the time of PCI, the patients were divided into single PCI group (1 218 cases) and staged PCI group (614 cases). The patients were followed up for 2 years, the primary endpoint was major cardiovascular and cerebrovascular event (MACCE), including target vessel-related myocardial infarction (TV-MI), target vessel-related revascularization (TVR), cardiogenic death and stroke, and the secondary endpoint was stent thrombosis. The propensity score matching (PSM) was applied to balance the discrepancies between 2 groups, and the baseline and follow-up data were compared. The Kaplan-Meier survival curves were drawn to evaluate the survival rates events; multifactor Cox proportional risk regression was used to analyze whether staged PCI was an independent risk factor for the endpoint events.Results:The in-hospital stay, duration of procedure and synergy between percutaneous coronary intervention with taxus and cardiac surgery (SYNTAX) score in single PCI group were significantly lower than those in staged PCI group: (5.54±3.09) d vs. (9.50±4.06) d, (43.12±28.55) min vs. (79.54±44.35) min, (14.04±7.63) scores vs. (18.51±7.79) scores, and there were statistical differences ( P<0.01); there were no statistical difference in complete revascularization rate and SYNTAX score after PCI between 2 groups ( P>0.05). Based on 2-year follow-up, the incidences of TV-MI and stent thrombosis in staged PCI group were significantly higher than those in single PCI group: 2.1% (13/614) vs. 0.5% (6/1 218) and 2.0% (12/614) vs. 0.4% (5/1 218), and there were statistical differences ( P<0.01). Kaplan-Meier survival curves analysis results showed that the event-free survival rates of TV-MI and stent thrombosis in single PCI group were better than those in staged PCI group (99.5% vs. 97.9% and 99.6% vs. 98.0%, P<0.01). Multifactor Cox proportional risk regression analysis results showed that staged PCI was an independent risk factor for stent thrombosis ( HR = 3.91, 95% CI 1.25 to 12.18, P = 0.019). After PSM, the incidences of TV-MI and stent thrombosis in staged PCI group were significantly higher than those in single PCI group: 2.1% (13/614) vs. 0.7% (4/614) and 2.0% (12/614) vs. 0.5% (3/614), and there were statistical differences ( P<0.05); Kaplan-Meier survival curve analysis results showed that the event-free survival rates of TV-MI and stent thrombosis in single PCI group were significantly higher than those in staged PCI group: (99.3% vs. 97.9% and 99.5% vs. 98.0%, P<0.05); multifactor Cox proportional risk regression analysis results showed that staged PCI was not an independent risk factor of stent thrombosis ( HR = 2.29, 95% CI 0.58 to 9.00, P = 0.234). Both before and after PSM, there were no evidences for interaction between the type of angina pectoris and staged PCI ( P>0.05). Conclusions:Although a seemingly increase exists in the incidence of TV-MI and stent thrombosis in the staged PCI group, staged PCI is an independent risk factor neither for MACCE and its components, nor for stent thrombosis. In addition single PCI reduces the in-hospital days and duration of PCI procedure, which may be a relatively reasonable approach to clinical practice.

Bisecting N-acetylglucosamine(GlcNAc),a GlcNAc linked to the core β-mannose resi-due via a β1,4 linkage,is a special type of N-glycosylation that has been reported to be involved in various biological processes,such as cell adhesion and fetal development.This N-glycan structure is abundant in human trophoblasts,which is postulated to be resistant to natural killer cell-mediated cytotoxicity,enabling a mother to nourish a fetus without rejection.In this study,we hypothesized that the human amniotic membrane,which serves as the last barrier for the fetus,may also express bisected-type glycans.To test this hypothesis,glycomic analysis of the human amniotic membrane was performed,and bisected N-glycans were detected.Furthermore,our pro-teomic data,which have been previously employed to explore human missing proteins,were ana-lyzed and the presence of bisecting GlcNAc-modified peptides was confirmed.A total of 41 glycoproteins with 43 glycopeptides were found to possess a bisecting GlcNAc,and 25 of these gly-coproteins were reported to exhibit this type of modification for the first time.These results provide insights into the potential roles of bisecting GlcNAc modification in the human amniotic membrane,and can be beneficial to functional studies on glycoproteins with bisecting GlcNAc modifications and functional studies on immune suppression in human placenta.

Objective ToassessthevalueofGdGEOBGDTPAenhancedT1ρimaginginevaluatingtheseverityandinflammation gradeinnonalcoholicsteatohepatitis(NASH)rabbitsmodel.Methods NASH modelswereestablishedin26adultrabbitsbyfeeding withthehighGfat,highGcholesteroldietinavarieddurations (0,4,8,12 weeks).T1ρ,T1ρinthehepatobiliaryphase (HBP)and changeofT1ρ(Δ%)werecomparedamongthedifferentgroupswhichweredeterminedbydifferentnonGalcoholicfattyliverdisease activityscore(NAS)andinflammationgrades.SpearmancorrelationanalysiswasusedtoassessthecorrelationsofT1ρ,T1ρ(HBP) withNASscoresandinflammationgrades.ROCcurvewasperformedtoevaluatethediagnosticvalueofT1ρ,T1ρ(HBP)inpredicting NASHandadvancedinflammation.Results T1ρandT1ρ(HBP)werepositivelyassociatedwithNASandinflammationscores.The differencesofT1ρ(HBP)amongNASH,nonalcoholicfattyliver(NAFL)andnormalliverwerestatisticallysignificant(P＜0.05). T1ρ(HBP)wassignificantlydifferentintherabbitswithgrade3inflammationfromintherabbitswithgrade0,grade1andgrade2 inflammation (P＜0.05).AUCsofT1ρandT1ρ(HBP)fordifferentiatingNASH were0.849and0.949,respectively.AUCofT1ρand T1ρGHBPfordiagnosinggrade2andgrade3inflammationwere0.925and0.922,respectively.Fibrosisandinflammationwerethe mainindependentfactorsaffectingT1(HBP).Conclusion GdGEOBGDTPAenhancedT1ρimagingcanreflecttheseverityofNASH anddegreeofinflammation.T1ρ(HBP)mightbeamoresuperiornoninvasiveimagingbiomarkerthannonGenhancedT1ρforassessmentof NASHactivityandinflammationgrading.

Objective: To observe the impact and clinical outcome of intra-aortic balloon pump(IABP) use in patients underwent percutaneous coronary intervention (PCI). Methods: From January 2013 to December 2013, 10 724 consecutive patients undergoing PCI were enrolled.After 2 years′ follow-up, the incidence of major adverse cardiovascular and cerebrovascular events such as death, myocardial infarction, stent thrombosis, revascularization, recurrent stroke were recorded, propensity score was used to match baseline data, and the clinical outcomes in patients with IABP and non-IABP were compared. Results: The overall use of IABP was 1.3%(143/10 724), clinical and angiographic risks were significantly higher in IABP group than non-IABP group.The rate of cardiac shock was significantly higher (9.8%(14/143) vs. 0.2%(16/10 581), P<0.01) and left ventricular ejection fraction was significantly lower (54.3%±11.0% vs. 62.9%±7.2%, P<0.01) in the IABP group than in the non-IABP group.Patients in IABP group had a significantly higher rate of left main or triple-vessel disease (P<0.01), and their SYNTAX score, target lesion number, stent number were also significantly higher compared with non-IABP patients (all P<0.01). During the 2-year follow-up, all-cause mortality was significantly higher in IABP group than in non-IABP group (10.5%(15/142) vs. 1.1%(116/10 581), P<0.001). Multivariable analyses indicated that IABP was associated with increased mortality (HR=3.51, 95%CI 1.71-7.17, P=0.001). However, after propensity score matched analyses (137 pairs), IABP use was no longer an independent predictor of all-cause mortality (HR=2.09, 95%CI 0.72-6.13, P=0.177). Conclusions In this single large center of coronary heart disease in China, the IABP usage was about 1.3%.Propensity score matched analyses showed that during the 2 years′ follow-up, adverse effect including similar long-term mortality is similar between PCI patients with or without IABP after adjusting for confounders.

Objective To investigate the surgical methods and experience of laparoscopic radical cystectomy and orthotopic ileal neobladder for invasive bladder cancer. Methods The clinical data of 14 patients with invasive bladder cancer underwent laparoscopic radical cystectomy and orthotopic ileal neobladder were collected retrospectively during March 2011 and October 2014. Results The 13 patients with invasive bladder cancer were successfully completed laparoscopic radical cystectomy and orthotopic ileal neobladder. 1 case was treated with laparotomy because of unsatisfactory surgery ifeld caused by excessive tumor bleeding. Twelve cases of the urethra-neobaldder anastomosis were completed through the abdominal incision, while for the other 2 cases, the anastomosis was done under the laparoscope, 2 cases were performed neovesicourethral anastomosis using single-needle running sutures through laparoscopy. The median operative time was 444 minutes, the mean intraoperative blood loss was 490 ml. Postoperative pathologic results conifrmed that 12 cases were bladder transitional cell carcinoma (1 case with partial squamous cell carcinoma) and 2 cases with bladder adenocarcinoma. No severe complication occurred except for 2 cases of urinary leakage and 1 case of urinary incontinence. Patients were followed up for 6-56 months,within which 3 patients were died of distant metastasis, 1 case was detected with intracranial metastasis, 1 case was found with urethra-vesical anastomotic stenosis while cured after urethrotomy. Ten cases were well recovered and the mean volume of the neobladder was 300 ml. Conclusions Laparoscopic radical cystectomy and orthotopic ileal neobladder have the advantage of better therapeutic effects, safety, minimal invasion and rapid recovery, which are the preferred therapeutic methods for invasive bladder cancer.