ObjectiveTo investigate the mechanism of action of remifentanil （RMZL） in alleviating lung ischemia-reperfusion injury （LIRI） in rats by inhibiting pyroptosis through modulating hypoxia inducible factor-1α （HIF-1α）/NOD-like receptor thermal protein domain associated protein 3 （NLRP3） pathway. MethodsRats were stochastically assigned into Control group， LIRI group， RMZL low-dose group， RMZL medium-dose group， RMZL high-dose group， and RMZL high-dose+HIF-1α activator dimethyloxallyl glycine （DMOG） group， with 18 rats in each group. Rats in Control group only had their left pulmonary hilum free and did not undergo ischemia-reperfusion treatment. Except for the Control group， LIRI models were constructed in all other groups. Rats in LIRI group were intraperitoneally injected with an equal amount of physiological saline 15 minutes before constructing LIRI model； rats in Control group were intraperitoneally injected with an equal amount of physiological saline 15 minutes before freeing left pulmonary hilum； rats in other groups were intraperitoneally injected with corresponding dose of drug 15 minutes before constructing LIRI model. The wet/dry weight ratio of lungs was calculated. HE staining was used to study lung tissue pathology. Immunofluorescence staining was used to detect the relative fluorescence intensity of gasdermin D （GSDMD） and NLRP3 double positive cells in lung tissue. ELISA was used to detect interleukin-1β and IL-18 in lung tissue. Western blot was used to detect HIF-1α， NLRP3， cysteine-aspartic protease-1 （Cleaved caspase-1）， and gasdermin D-N （GSDMD-N） proteins in lung tissue. ResultsCompared to the Control group， the LIRI group showed disordered alveolar structure， thickened alveolar septa， and abundant inflammatory cell infiltration in rats. The lung wet/dry weight ratio， relative fluorescence intensity of GSDMD and NLRP3 double positive cells in lung tissue， IL-1β， IL-18 levels， and HIF-1α， NLRP3， Cleaved caspase-1， and GSDMD-N proteins increased （P0.05）. For the LIRI group， rats in the RMZL low， medium， and high-dose groups displayed attenuated alveolar septal thickening and reduced inflammatory cell infiltration. The lung wet/dry weight ratio， relative fluorescence intensity of GSDMD and NLRP3 double positive cells in lung tissue， IL-1β， IL-18 levels， and HIF-1α， NLRP3， Cleaved caspase-1， and GSDMD-N proteins declined， and the RMZL high-dose group showed the most prominent trend （P0.05）. Compared with the RMZL high-dose group， rats in the RMZL high-dose+DMOG group exhibited thickened alveolar septa and more inflammatory cell infiltration， along with increased lung wet/dry weight ratio， relative fluorescence intensity of GSDMD and NLRP3 double positive cells in lung tissue， levels of IL-1β and IL-18， and protein expression of HIF-1α， NLRP3， Cleaved caspase-1， and GSDMD-N （P0.05）. ConclusionRMZL may inhibit pyroptosis in LIRI rats by suppressing HIF-1α/NLRP3 pathway.

Objective:To construct a lentiviral interference plasmid targeting collapse response regulatory protein 1(CRMP1)gene,to establish a human neuroblastoma cell line(SH-SY5Y)with stable CRMP1 knockdown,and to investigate its impact on expression of NLRP3 inflammasome protein.Methods:Double-stranded shRNA was designed and synthesized targeting h-CRMP1 mRNA sequence,and cloned into PLKO.1 vector.Recombinant shCRMP1 plasmids were constructed correctly,which was transfected into HEK-293T cells for lentiviral packaging.Obtained lentivirus supernatant was concentrated and then infected into SH-SY5Y cells.The interference effect of shCRMP1 plasmid and protein expressions of NLRP3 inflammasome components in SH-SY5Y cells were detected by Western blot.Results:DNA sequencing results showed that insertion sequences of recombinant interference plasmids pLKO.1-shCRMP1 were consistent with designed sequences,which confirmed successful construction of shCRMP1 lentivirus interfering plasmids and transfected into HEK-293T cells for lentivirus packaging,and protein level of CRMP1 in HEK-293T cells were decreased.SH-SY5Y cells were infected with lentivirus concentrate obtained from packaging and screened with puromycin.Western blot results showed that shCRMP1 recombinant lentiviral plasmids could significantly down-regulate CRMP1 protein expression in SH-SY5Y cells.It was also found that in SH-SY5Y cell line with stable CRMP1 knockdown,inhibition of CRMP1 expression could effectively inhibit NLRP3 inflammasome activation under MPP+induction.Conclusion:pLKO.1-shCRMP1 lentiviral interfering plas-mids have been successfully constructed,and interference with CRMP1 can inhibit activation of NLRP3 inflammasome in MPP+-in-duced SH-SY5Y cells.This study provides guidance for further research on mechanism of CRMP1 in neurodegenerative diseases such as Parkinson's disease.

A microchannel-based electrochemiluminescence(ECL)sensor was developed for detection of tetracycline(TC)utilizing luminol/H2O2 as ECL reporting system.The low excitation potential of luminol/H2O2 effectively mitigated the impact of clamping voltage,thereby enhancing the detection performance of the microchannel-based ECL sensor.The microchannel modified with TC aptamer selectively recognized and captured target TC.The positively charged TC reduced the surface charge density within the microchannel,thereby increasing the ionic current in the microchannel,leading to change of ECL signal of system.The experimental conditions such as electrolyte concentration,TC-aptamer concentration,and reaction time between TC and TC-aptamer were optimized.Under optimal conditions,the difference of ECL signal in the absence and presence of TC(?ECL)exhibited a good linear relationship with TC concentration in the range from 1.00 ng/mL to 200 ng/mL,with a detection limit as low as 0.69 ng/mL.The sensor had good selectivity and was successfully used in detection of TC in milk samples.

Objective:To investigate spinal cord morphological changes and risk factors in upper cervical spine surgery using C 2 medial "in-out-in" pedicle screws in patients with atlantoaxial dislocation (AAD) and high-riding vertebral artery (HRVA). Methods:A retrospective analysis was conducted on 41 patients with AAD who underwent C 2 medial "in-out-in" pedicle screw implantation at our hospital between January 2019 and December 2023. The cohort included 12 males and 29 females, with a mean age of 47.6±10.3 years (range: 18-68 years). Among them, 30 patients received unilateral C 2 medial "in-out-in" screws, while 11 patients received bilateral screws. All patients underwent posterior reduction and internal fixation. Measurements included C 2 pedicle height, C 2 pedicle width, C 2 horizontal spinal canal width, screw invasion distance into the spinal canal, and spinal canal invasion rate based on CT findings. MRI evaluations included spinal canal-dura mater distance, dura mater-spinal cord distance, spinal canal-spinal cord distance, and spinal cord cross-sectional area. The change rate of spinal cord cross-sectional area was calculated and categorized into >20% decrease group (decreasing group) and ≤20% decrease group (non-decreasing group). Postoperative outcomes were assessed using the Visual Analogue Scale (VAS) and Japanese Orthopedic Association (JOA) scores. Results:The mean operative time was 165.5±30.1 minutes (range: 120-220 minutes). No spinal cord vascular injuries or severe complications were observed. However, five patients experienced cerebrospinal fluid (CSF) leakage, requiring delayed removal of drainage tubes, but their wounds healed successfully. Follow-ups (range: 6-24 months) showed no loosening of internal fixation, fractures, or bone graft nonunion, with a 100% bone fusion rate at 6 months postoperatively. VAS scores improved significantly from a preoperative median of 5.0 (3.5, 6.0) (range: 1-7) to 2.0 (2.0, 3.0) at 3 months and 1.0 (1.0, 1.0) at 6 months ( Z=36.716, P< 0.001). JOA scores improved from 10.0 (9.0, 12.0) (range: 4-14) preoperatively to 13.0 (11.0, 13.5) at 3 months and 14.0 (12.0, 15.0) at 6 months ( Z=67.093, P<0.001). The height of C 2 pedicle was 5.50±1.78 mm, the width of C 2 pedicle was 2.27±1.23 mm, the width of C 2 horizontal spinal canal was 23.76±4.91 mm, the spinal canal-dura mater distance was 3.08±0.85 mm, dura mater-spinal cord distance was 3.23±0.85 mm, the spinal canal-spinal cord distance was 6.31±1.11 mm, the distance of screw invasion into the spinal canal was 2.80±1.54 mm, the rate of spinal canal invasion was 12.1%±6.8%, the preoperative spinal cord cross-sectional area was 69.81±13.27 mm 2, and the postoperative spinal cord cross-sectional area was 68.81±13.94 mm 2. Based on spinal cord cross-sectional area changes, 32 patients were classified into the non-decreasing group, and 9 patients into the decreasing group. The intraclass correlation coefficient (ICC) values ranged from 0.733 to 0.984, indicating high measurement reliability. There were significant differences in the proportion of C 2 bilateral medial "in-out-in" screws (χ 2=6.903, P=0.009), the incidence of CSF leakage (χ 2=15.391, P<0.001), the distance of screw invasion into the spinal canal ( t=4.990, P<0.001) and the rate of spinal canal invasion ( t=4.045, P<0.001) in the decreasing group versus the non-decreasing group. The JOA scores of the non-decreasing group were significantly higher at 3 and 6 months postoperatively compared to the decreasing group ( P<0.05). No other parameters showed significant differences between the groups. Binary logistic regression analysis identified spinal canal invasion rate [ OR=1.963, 95% CI (1.010, 3.817), P=0.047] as an independent risk factor for spinal cord cross-sectional area reduction. The Jordan index was 0.875, with a spinal canal invasion rate threshold of 14.18%, a sensitivity of 1.000, a specificity of 0.875, and an AUC of 0.983, indicating strong predictive value. Conclusion:The C 2 medial "in-out-in" screw technique provides effective posterior fixation and fusion for AAD patients with HRVA. However, to minimize spinal cord morphological changes and associated risks, the spinal canal invasion rate should be kept below 14.18% when using this technique.

Thyroid eye disease(TED), also known as thyroid-associated ophthalmopathy(TAO) or Graves' ophthalmopathy(GO), is an organ-specific autoimmune disorder associated with autoimmune thyroid disease and can severely impair vision and quality of life. The pathogenesis of TED is closely linked to dysregulated cytokine networks; however, current therapies yield limited response rates in patients with moderate-to-severe TED. This review synthesizes the mechanisms of action of key cytokines and evaluates the translational potential of emerging targeted therapies, aiming to provide a rationale for overcoming current therapeutic bottlenecks and advancing precision treatment strategies.

Objective:To evaluate the effectiveness of fosaprepitant in preventing postoperative nausea and vomiting (PONV) following gynecological laparoscopic surgery.Methods:In this randomized parallel-controlled trial, 100 American Society of Anesthesiologists Physical Status classification Ⅰ or Ⅱ patients, aged 18-64 yr, undergoing elective gynecological laparoscopic surgery under general anesthesia at the First Affiliated Hospital of Zhengzhou University, were selected and divided into 2 groups ( n=50 each) in a ratio of 1∶1 using blocked randomization: fosaprepitant group (group F) and tropisetron group (group T). At 30 min before anesthesia induction, fosaprepitant 150 mg was intravenously infused in group F, and tropisetron 5 mg was intravenously infused in group T, both diluted in 150 ml of normal saline. Anesthesia was induced by intravenous injection of midazolam, etomidate, sufentanil and cisatracurium. Anesthesia was maintained by intravenous infusion of remifentanil and propofol. Patient-controlled intravenous analgesia was performed with hydromorphone at the end of operation until 48 h after operation. Metoclopramide was given as rescue antiemetic. The PONV, requirement for antiemetic drugs and related adverse reactions were recorded within 24 h after surgery. Results:The incidence of PONV (10% vs 30%), the incidence of vomiting(2% vs 16%) and the rescue rate of antiemetic drugs(2% vs 12%)were significantly lower in group F than in group T ( P<0.05). There was no significant difference in the incidence of related adverse reactions between the two groups ( P>0.05). Conclusions:Intravenous infusion of fosaprepitant 150 mg at 30 min before anesthesia induction effectively prevents PONV in patients undergoing gynecological laparoscopic surgery, and the efficacy is superior to that of the conventional use of tropisetron.

Objective:To investigate the correlation between membranous urethral length (MUL) and early urinary continence recovery after robot-assisted radical prostatectomy (RARP).Methods:A retrospective analysis was conducted on 71 prostate cancer patients who underwent RARP by a single surgeon at the PLA General Hospital between January 2020 and December 2023. Patient characteristics included: age of (65.32±6.04) years, BMI (25.21 ± 2.59) kg/m 2, prostate volume 32.41 (24.75, 44.40) ml, PSA 11.67 (8.22, 22.66) ng/ml. Gleason score [6/7/8/9-10: 15 (21.2%)/29 (40.8%)/16 (22.5%)/11 (15.5%)], Clinical stage [cT 1/cT 2/cT 3: 4 (5.6%)/61 (85.9%)/6 (8.5%)]. Measured MUL using multiparametric prostate MRI, median MUL was 13.25 (10.41-14.99) mm. Neurovascular bundle (NVB) preservation in 13 (18.3%) cases. Patients were grouped based on continence recovery at 1 and 3 months post-catheter removal. Age, BMI, prostate volume, PSA, Gleason score, clinical stage, NVB preservation, pathological stage, catheter indwelling time, and MUL were compared between groups. Multivariate analysis identified independent predictors of continence recovery. Results:All 71 surgeries were successful, pathological stage [pT 2/pT 3-4: 47 (66.2%)/24 (33.8%)], and catheter indwelling time 2.7 (2.0, 3.0) weeks. Follow-up data at 2 months were available for 71 patients, at 1 month, 42 patients achieved continence (continence group) and 29 had incontinence (incontinence group).No significant differences were observed between continence and incontinence groups in age [(64.93±6.48)years vs. (65.79±5.89) years], BMI [(26.26±2.52)kg/m 2 vs. (24.52±2.42) kg/m 2], prostate volume [32.00 (24.12, 41.11)ml vs. 33.00 (25.27, 47.97) ml], PSA [12.55 (8.31, 24.00) ng/ml vs. 11.30 (7.92, 20.65) ng/ml], Gleason score [6/7/8/9-10: 6 (14.2%)/18 (42.9%)/12 (28.6%)/6 (14.3%) vs. 9 (31.0%)/11 (37.9%)/4 (13.8%)/5 (17.3%)], clinical stage [cT 1/cT 2/cT 3: 2 (4.8%)/35 (83.3%)/5 (11.9%) vs. 2 (6.9%)/26 (89.7%)/1 (3.4%)], NVB preservation [7 (16.7%) vs. 6 (20.7%)], pathological stage [pT 2/pT 3-4: 27 (64.3%)/15 (35.7%) vs. 20 (69.0%)/9 (31.0%)], or catheter indwelling time [2.6(2.0, 3.0) weeks vs. 2.9 (2.0, 3.4) weeks]. However, MUL was significantly longer in the continence group [13.77 (11.70, 15.32) mm vs. 10.32 (9.65, 13.57) mm, P<0.01]. Follow-up data at 3 months were available for 69 patients, At 3 months, 61 patients achieved continence (continence group) and 8 remained incontinent (incontinence group). No significant differences were observed in age [(64.89±6.25)years vs. (68.13±4.09) years], BMI [(25.34±2.64)kg/m 2 vs. (24.36±2.49) kg/m 2], prostate volume [32.41 (24.44, 44.16)ml vs. 36.13 (27.48, 48.26) ml], PSA [12.50 (8.28, 22.76)ng/ml vs. 13.34 (5.88, 23.39) ng/ml], Gleason score [6/7/8/9-10: 12 (19.7%)/25 (41.0%)/14 (23.0%)/10 (16.3%) vs. 3 (37.5%)/3 (37.5%)/2 (25.0%)/0], clinical stage [cT 1/cT 2/cT 3: 3 (4.9%)/52 (85.2%)/6 (9.8%) vs. 1 (12.5%)/7 (87.5%)/0], NVB preservation [9 (14.8%) vs. 3 (37.5%)], pathological stage [pT 2/pT 3-4: 41 (67.2%)/20 (32.8%) vs. 5 (62.5%)/9 (31.0%)], or catheter indwelling time [2.7(2.0, 3.0)weeks vs. 3.0 (2.3, 3.7) weeks]. MUL remained significantly longer in the continence group [13.57 (10.57, 15.10)mm vs. 10.12 (9.36, 10.42) mm, P=0.002]. Multivariate logistic regression incorporating age, BMI, prostate volume, MUL, NVB preservation, and catheter indwelling time identified MUL as an independent protective factor for continence recovery at both 1 month [ OR=0.62, 95 CI 0.49-0.79, P<0.01] and 3 months [ OR=0.61, 95 CI 0.41-0.92, P=0.017]. Conclusions:MUL is independently associated with early urinary continence recovery after RARP, serving as a protective predictor at both 1 and 3 months after catheter removal.

Objective:To investigate the risk factors for positive surgical margins（PSM）after robot-assisted radical prostatectomy（RARP），and to develop and validate a predictive nomogram.Methods:We retrospectively analyzed the clinicopathological data of 874 prostate cancer patients who underwent RARP performed by a single surgeon at the First Medical Center of Chinese PLA General Hospital between January 2012 and December 2018. Patients were divided into positive surgical margin（n=327）and negative surgical margin（n=547）groups based on postoperative margin status.The PSM group had significantly higher preoperative median tPSA［31.200（19.050，54.400）ng/ml vs. 15.050（9.840，27.590）ng/ml， P<0.01］，higher proportion of patients with PSAD>1 ng/ml 2［49.5%（162/327）vs. 21.2%（116/547）， P<0.01］，biopsy Gleason score ≥8［33.3%（109/327）vs. 21.2%（116/547）， P<0.01］，ISUP grade 4-5［33.3%（109/327）vs. 21.2%（116/547）， P<0.01］，clinical T stage ≥cT 3［11.3%（37/327）vs. 4.2%（23/547）， P<0.01］，and high-risk classification［82.3%（269/327）vs. 55.9%（306/547）， P<0.01］compared to the negative surgical margin group. Conversely，the PSM group had a lower prevalence of hypertension［29.7%（97/327）vs. 40.2%（220/547）， P=0.002］.Patients were randomly split into a training cohort（n=656，75%）and an internal validation cohort（n=218，25%）. An external validation cohort included 71 patients who underwent RARP by different surgeons between January 2014 and December 2016. No significant differences in baseline characteristics were observed between cohorts（ P>0.05）.Univariate and multivariate logistic regression analyses identified independent predictors of PSM，which were incorporated into a nomogram. Predictive performance was assessed using receiver operating characteristic（ROC）curves，decision curve analysis（DCA），and calibration curve. Internal and external validations were performed. Results:The PSM group had longer postoperative hospitalization［6（5，8）vs. 6（5，7）days， P=0.028］，higher rates of pathologic Gleason score ≥8［41.5%（115/277）vs. 24.9%（111/446）， P<0.01］，ISUP grade 4-5［41.5%（115/277）vs. 24.9%（111/446）， P<0.01］，pT 3 stage［52.3%（171/327）vs. 17.4%（95/547）， P<0.01］，pN 1 stage［12.8%（42/327）vs. 3.8%（21/547）， P<0.01］，extracapsular extension［52.3%（171/327）vs. 17.4%（95/547）， P<0.01］，and seminal vesicle invasion［34.6%（113/327）vs. 9.1%（50/547）， P<0.01］.Multivariate analysis identified elevated tPSA（ OR=1.014，95% CI 1.004—1.024，P=0.006）and PSAD ≥0.15 ng/（ml/g）（ OR=11.638，95% CI 1.450—93.396，P=0.021）as independent risk factors for PSM. The area under the ROC curve（AUC）of the nomogram constructed based on the above variables was 0.770（95% CI 0.735—0.805）. The AUC values for the internal and external validation sets were 0.698（95% CI 0.630—0.767）and 0.643（95% CI 0.513—0.774），respectively. The calibration curve demonstrated good agreement between the predicted and observed outcomes，and the DCA indicated that the predictive model has potential clinical utility in decision-making. Conclusion:tPSA and PSAD were identified as independent risk factors for PSM. The nomogram constructed based on these two independent predictive variables effectively predicted PSM after RARP.

Aim To investigate the role and regulatory mechanism of CREB regulated transcription coactivator 2(CRTC2)in cardiomyocyte hypertrophy.Methods A pathological cardiomyocyte hypertrophy model was established in C57BL/6 mice by intraperitoneal injection of isoproterenol(ISO),the expression of CRTC2 in cardiac tissue was detec-ted by Western blot.The CRTC2 knockout mice model was constructed,the cardiac function of mice was detected by small animal echocardiography,the collagen fiber content in mice cardiac tissue was detected by Masson staining,the car-diomyocyte hypertrophy related proteins:skeletal muscle α1-actin(ACTA1)and brain natriuretic peptide(BNP),as well as ferroptosis related proteins:acyl-CoA synthetase long chain family member 4(ACSL4),solute carrier family 7 member 11(SLC7A11)and glutathione peroxidase 4(GPX4)in mice cardiac tissue were detected by Western blot,the iron ion content in mice cardiac tissue was detected by iron ion kit,to evaluate the correlation between CRTC2 and cardiomyocyte hypertrophy and ferroptosis.H9c2 cells were induced by ISO to construct an in vitro model of cardiomyocyte hypertrophy,the protein expressions of CRTC2,ACTA1,BNP,ACSL4,SLC7A11 and GPX4 were detected after intervention with fer-roptosis inhibitor ferrostatin-1(Fer-1).H9c2 cells with CRTC2 overexpression induced by ISO were used to construct an in vitro model of cardiomyocyte hypertrophy,the related indicators of cardiomyocyte hypertrophy and ferroptosis were detec-ted to explore the mechanism of CRTC2 in cardiomyocyte hypertrophy.Results Compared with the control group,the expression of CRTC2 protein in the cardiac tissue of ISO induced cardiomyocyte hypertrophy mice was increased(P＜0.05).Compared with wild-type mice,CRTC2-/-mice showed worsened cardiac function,manifested as increased left ventricular end-diastolic diameter(LVEDD),left ventricular end-systolic diameter(LVESD),left ventricular posterior wall thickness(LVPWT),heart weight/tibia length(HW/TL)and heart weight/body weight(HW/BW),decreased short axis shortening(FS)and ejection fraction(EF),increased collagen fiber content in cardiac tissue,upregulated ex-pression of cardiomyocyte hypertrophy-related proteins ACTA1 and BNP,increased mRNA and protein expression of ferrop-tosis-related protein ACSL4,decreased mRNA and protein expression of SLC7A11 and GPX4,and elevated iron ion content in cardiac tissue(P＜0.05 or P＜0.01).In vitro experiments showed that compared with ISO group,the ISO+Fer-1 group had no significant change in CRTC2 protein expression(P＞0.05),the expression of ACTA1 and BNP protein decreased,the surface area of cardiomyocyte reduced,the expression of ACSL4 protein decreased,and the expression of SLC7A11 and GPX4 proteins increased(P＜0.05 or P＜0.01).Compared with the ISO group,the LV-CRTC2+ISO group showed a decrease in surface area of cardiomyocytes(P＜0.01),a decrease in ACTA1,BNP and ACSL4 protein ex-pression,an increase in SLC7A11 and GPX4 protein expression,and a decrease in ROS and iron ion content(P＜0.05 or P＜0.01).Conclusion CRTC2 alleviates cardiomyocyte hypertrophy and protect cardiac function by suppressing fer-roptosis in cardiomyocytes.