Objectives: . This study aimed to investigate the regulatory functions of gamma-aminobutyric acid (GABA)ergic neural circuits from the inferior colliculus (IC) to the medial geniculate body (MGB) in salicylate-induced tinnitus. Methods: . Mice were treated with salicylate to induce tinnitus, and tinnitus-like behaviors were evaluated via gap prepulse inhibition of acoustic startle. Using combined viral tracing methodologies, we identified and mapped the pathways and connections from the IC to the MGB. Furthermore, we employed Gq-coupled human M3 designer receptors exclusively activated by designer drugs (DREADDs) and Gi-coupled human M4 DREADDs to achieve targeted excitation or suppression of GABAergic neurons in the IC and MGB. Following the administration of clozapine N-oxide, which binds to these receptors, we modulated these neural circuits to assess their impact on tinnitus severity in a mouse model. Results: . Our findings demonstrated that mice exposed to salicylate exhibited tinnitus-like behaviors. GABAergic neurons projecting retrogradely from the MGB to the IC were primarily concentrated in the external nucleus of the IC. After clozapine N-oxide administration, chemogenetic activation of IC-MGB GABAergic neurons aggravated salicylate-induced tinnitus. Additionally, activation of GABAergic neurons between the IC and MGB induced the perception of tinnitus even without salicylate. However, chemogenetic inhibition of the IC-MGB GABAergic circuit did not reverse salicylate-induced tinnitus. Conclusion . These findings suggest that activation of the IC-MGB GABAergic neural circuit may contribute to tinnitus generation through a mechanism distinct from that of salicylate-induced tinnitus. This study provides novel insights into the mechanisms underlying tinnitus.

Objective: To evaluate the feasibility of dynamic contrast-enhanced MRI (DCE-MRI) in differentiating tumor deposits (TDs) from metastatic lymph nodes (MLNs) in rectal cancer. Materials and Methods: A retrospective analysis was conducted on 70 patients with rectal cancer, including 168 lesions (70 TDs and 98 MLNs confirmed by histopathology), who underwent pretreatment MRI and subsequent surgery between March 2019 and December 2022. The morphological characteristics of TDs and MLNs, along with quantitative parameters derived from DCE-MRI (K trans , kep, and v e) and DWI (ADCmin, ADCmax, and ADCmean), were analyzed and compared between the two groups.Multivariable binary logistic regression and receiver operating characteristic (ROC) curve analyses were performed to assess the diagnostic performance of significant individual quantitative parameters and combined parameters in distinguishing TDs from MLNs. Results: All morphological features, including size, shape, border, and signal intensity, as well as all DCE-MRI parameters showed significant differences between TDs and MLNs (all P < 0.05). However, ADC values did not demonstrate significant differences (all P > 0.05). Among the single quantitative parameters, v e had the highest diagnostic accuracy, with an area under the ROC curve (AUC) of 0.772 for distinguishing TDs from MLNs. A multivariable logistic regression model incorporating short axis, border, v e, and ADC mean improved diagnostic performance, achieving an AUC of 0.833 (P = 0.027). Conclusion The combination of morphological features, DCE-MRI parameters, and ADC values can effectively aid in the preoperative differentiation of TDs from MLNs in rectal cancer.

Objective To investigate the clinical prognosis of untreated residual coronary artery dissection treated with drug coated balloon(DCB).Methods A retrospective analysis was conducted on the clinical and imaging data of patients with primary coronary artery lesions(2.5-4.0 mm)treated with DCB under angiography guidance at Xuzhou Cancer Hospital,Xuzhou New Health Geriatric Hospital,and Peixian Guotai Hospital from September 2017 to April 2023.According to the observation of coronary artery dissection through angiography,the patients were divided into a dissection group and a non dissection group.The main endpoint of this study was the major adverse cardiovascular event(MACE)during a 12-month follow-up.Results A total of 381 patients were enrolled in the three research centers,with 30 cases(30 lesions)in the dissection group and 351 cases(367 lesions)in the non dissection group.There was no significant difference between the two groups in terms of age,gender,hypertension,hyperlipidemia,diabetes,smoking,previous myocardial infarction,previous percutaneous coronary intervention,coronary artery bypass grafting and other baseline clinical characteristics(all P＞0.05).Except for the reference vessel diameter(P=0.049)and DCB pressure(P=0.032),there was no statistically significant difference in the characteristics of coronary angiography lesions between the two groups of patients(both P＞0.05).During a 12-month follow-up,there was no statistically significant difference(P＞0.05)in the incidence of MACE between the dissection group and the non dissection group after DCB treatment for primary coronary artery lesions in situ.Conclusions Untreated residual dissection after DCB treatment of de novo coronary lesions does not lead to an increase in clinical MACE.

The ocean plays a critical role in the global carbon cycle,and base on the"dual carbon"goals,ocean carbon sinks have received widespread attention.Shellfish aquaculture is one of the most important sources of carbon sinks in fisheries,which has an important impact on the offshore carbon cy-cle.As global temperature rises and ocean acidification intensifies,the capacity of the ocean to absorb CO2 will change.However,the effects of high temperature on the physiology and transcriptome related to carbon metabolism in Mytilus coruscus are not clear enough.This study investigated the effects of high temperatures on the total carbon content,carbon metabolism,antioxidant-related enzyme activities,and the transcriptome of Mytilus coruscus.The results showed that high temperature significantly inhibited the activities of hexokinase and pyruvate kinase,increased carbonic anhydrase activity(P＜0.05),de-creased the ATP content of digestive glands(P＜0.05),and affected glycolysis and the tricarboxylic acid cycle,leading to a significant decrease in the mussel's ability to sequester carbon.High temperature re-sulted in significant(P＜0.05)increases in the levels of reactive oxygen species and malondialdehyde,and enhanced the activities of superoxide dismutase and catalase.Observations by transmission electron microscopy showed that high temperatures damaged the subcellular structure of the digestive gland in Mytilus coruscus,resulting in the shrinkage of the nucleolus,swelling of the endoplasmic reticulum,and a significant reduction in the mitochondrial cristae.Comparative transcriptomic analysis showed that the upregulated DEGs were mainly enriched in protein processing in the endoplasmic reticulum,antigen pro-cessing and presentation,and MAPK signaling pathway.The downregulated DEGs were mainly enriched in necroptosis,DNA replication,and the NF-kappa B signaling pathway.In antioxidant-related DEGs,the upregulated DEGs include vitamin K epoxide reductase,peroxidases,heat shock protein 105 kD,heat shock protein 70 kD,and superoxide dismutase;The downregulated DEGs mainly included NADPH oxidase,glutathione reductase,cytochrome b-245,cytochrome P450,and quinone reductase.The up-regulated genes enriched in the carbon metabolism pathway included chitinase,phosphatidylinositol 4,5-bisphosphate 3-kinase,phosphoenolpyruvate carboxykinase,galactokinase,and inositol trisphosphate 3-kinase.The downregulated genes included aldose-1-epimerase,carbonic anhydrase,galactose mutaro-tase,acyl-CoA synthetase,alcohol dehydrogenase,and hexokinase.In conclusion,high temperature has an inhibitory effect on the activities of enzymes and the expression of genes related to carbon metabolism in Mytilus coruscus.The results of this study are intended to provide a scientific basis for the healthy de-velopment of mussel aquaculture and the assessment of carbon sinks.

The ocean plays a critical role in the global carbon cycle,and base on the"dual carbon"goals,ocean carbon sinks have received widespread attention.Shellfish aquaculture is one of the most important sources of carbon sinks in fisheries,which has an important impact on the offshore carbon cy-cle.As global temperature rises and ocean acidification intensifies,the capacity of the ocean to absorb CO2 will change.However,the effects of high temperature on the physiology and transcriptome related to carbon metabolism in Mytilus coruscus are not clear enough.This study investigated the effects of high temperatures on the total carbon content,carbon metabolism,antioxidant-related enzyme activities,and the transcriptome of Mytilus coruscus.The results showed that high temperature significantly inhibited the activities of hexokinase and pyruvate kinase,increased carbonic anhydrase activity(P＜0.05),de-creased the ATP content of digestive glands(P＜0.05),and affected glycolysis and the tricarboxylic acid cycle,leading to a significant decrease in the mussel's ability to sequester carbon.High temperature re-sulted in significant(P＜0.05)increases in the levels of reactive oxygen species and malondialdehyde,and enhanced the activities of superoxide dismutase and catalase.Observations by transmission electron microscopy showed that high temperatures damaged the subcellular structure of the digestive gland in Mytilus coruscus,resulting in the shrinkage of the nucleolus,swelling of the endoplasmic reticulum,and a significant reduction in the mitochondrial cristae.Comparative transcriptomic analysis showed that the upregulated DEGs were mainly enriched in protein processing in the endoplasmic reticulum,antigen pro-cessing and presentation,and MAPK signaling pathway.The downregulated DEGs were mainly enriched in necroptosis,DNA replication,and the NF-kappa B signaling pathway.In antioxidant-related DEGs,the upregulated DEGs include vitamin K epoxide reductase,peroxidases,heat shock protein 105 kD,heat shock protein 70 kD,and superoxide dismutase;The downregulated DEGs mainly included NADPH oxidase,glutathione reductase,cytochrome b-245,cytochrome P450,and quinone reductase.The up-regulated genes enriched in the carbon metabolism pathway included chitinase,phosphatidylinositol 4,5-bisphosphate 3-kinase,phosphoenolpyruvate carboxykinase,galactokinase,and inositol trisphosphate 3-kinase.The downregulated genes included aldose-1-epimerase,carbonic anhydrase,galactose mutaro-tase,acyl-CoA synthetase,alcohol dehydrogenase,and hexokinase.In conclusion,high temperature has an inhibitory effect on the activities of enzymes and the expression of genes related to carbon metabolism in Mytilus coruscus.The results of this study are intended to provide a scientific basis for the healthy de-velopment of mussel aquaculture and the assessment of carbon sinks.

Objective To explore the effects of dodecanoylcarnitine(DA)and myristoleic acid(MA)on the function of mouse alveolar epithelial cell line MLE-12 and their underlying mechanisms.Methods An inflammatory model was established by stimulating MLE-12 cells with IL-4.The expression levels of DA,MA,and sphingosine-1-phosphate(S1P)in the cell supernatant were detected by ELISA.MLE-12 cells were separately intervened with DA and MA.RT-PCR and flow cytometry were used to detect the expression changes of inflammatory factors IL-6 and tumor necrosis factor-α(TNF-α)and the level of intracellular reactive oxygen species(ROS).Additionally,Western blot was performed to detect the expression of key proteins such as p38 mitogen-activated protein kinase(p-38 MAPK)and src homology 2 domain-containing phosphatase 1(SHP-1).To explore the role of S1PR2 in the effects of DA and MA,MLE-12 cells were pretreated with the S1PR2 inhibitor JTE-013,and the above experiments were repeated.Results IL-4 stimulation significantly upregulated the levels of DA,MA,and S1P in MLE-12 cells(P<0.05).DA/MA treatment groups exhibited significantly increased expression of IL-6 and TNF-α compared with the control group(P<0.05),along with elevated ROS levels(P<0.05).Western blot analysis revealed that DA/MA promoted SHP-1 dephosphorylation and phosphorylated p38 MAPK activation in MLE-12 cells.Notably,JTE-013 pre-treatment completely reversed these effects(P<0.05).Conclusion Asthma-related metabolites DA and MA exacerbate the inflammatory and oxidative stress responses of MLE-12 cells by activating the S1PR2 receptor,promoting the dephosphorylation of SHP-1 and the activation of the p-p38 MAPK pathway.This study reveals the core regulatory role of S1PR2 in this pathway as well.

Objective To investigate the clinical efficacy and safety of facilitated percutaneous coronary intervention(PCI)with half-dose recombinant staphylokinase(r-SAK)in patients with ST-segment elevation myocardial infarction(STEMI)who are expected to undergo PCI within 120 minutes.Methods From October 2021 to August 2022,a total of 200 STEMI patients in eight centers were included and randomly assigned in a 1﹕1 ratio to either r-SAK group or control group.Patients received loading doses of aspirin and ticagrelor and intravenous heparin and were randomized to receive an intravenous bolus of either 5 mg r-SAK or normal saline prior to PCI.The outcomes were set as ST-segment resolution(STR)at 60-90 minutes after PCI,the proportion and transition of pathological Q waves on the 5th day after PCI,and the proportion of high-sensitivity cardiac troponin T(hs-cTnT)peaking within 12 hours of onset.The safety outcome was major bleeding events defined as Bleeding Academic Research Consortium(BARC)≥type 3 bleeding during hospitalization.Results Compared with the control group,the r-SAK group had a higher proportion of STR≥70%within 60-90 minutes after PCI(58.3%vs.40.3%,P=0.009);a lower proportion of pathological Q waves(59.1%vs.74.1%,P=0.040);a lower rate of Q wave progression(14.8%vs.43.2%,P＜0.001);a higher rate of Q wave disappearance(12.5%vs.3.7%,P=0.027);and a higher proportion of hs-cTnT peaking within 12 hours of symptom onset[31/40(77.5%)vs.17/33(51.5%),P=0.027].Regarding the safety outcome,no significant difference in BARC≥type 3 bleeding was found between the two groups during hospitalization(P＞0.05).Conclusions For STEMI patients who were expected to undergo primary PCI within 120 minutes of symptom onset,the facilitated PCI with half-dose r-SAK significantly increased the proportion of STR≥70%at 60-90 minutes after PCI,reduced the formation of pathological Q waves,and shortened the time to peak hs-cTnT,without increasing the risk of bleeding,which should be an alternative reperfusion strategy worthy of further study.

Objective:This study aimed to evaluate the application effect of opioid-free anesthesia(OFA)in modified radical mastectomy for breast cancer.Methods:80 patients undergoing unilateral modified radical mastec-tomy were randomly divided into two groups:general anesthesia group(G group)and OFA group(O group).The G group received general anesthesia with opioid drugs and a laryngeal mask,while the O group received general anes-thesia with intravenous lidocaine combined with thoracic paravertebral nerve block and a laryngeal mask.The average arterial pressure(MAP)and heart rate(HR)of the patients were recorded at the time of admission(T0),induction(T1),start of surgery(T2),gland resection(T3),and admission to the recovery room(T4).The surgical time,awakening time,ex-tubation time,and getting out of bed time were recorded.The VAS score at 2 hours(T5),6 hours(T6),and 12 hours(T7)after surgery,as well as the systemic immune-inflammatory index(SII)before surgery(T8),6 hours after surgery(T9),and 12 hours after surgery(T10)were recorded.The occurrence of postoperative nausea and vomiting(PONV)and post-mastectomy pain syndrome(PMPS)were recorded.The occurrence of adverse events such as poor nerve block effect,pneumothorax,hematoma,and local anesthetic toxicity were also recorded.Results:The MAP and HR of the O group were more stable than those of the G group during surgery(P＜0.05).The awakening time,extubation time,and getting out of bed time in the O group were earlier than those in the G group(P＜0.05).The VAS and SII values after surgery were significantly lower in the O group than in the G group(P＜0.05).The incidence of PONV was also signifi-cantly decreased(P＜0.05).In addition,no adverse events such as pneumothorax,hematoma,or local anesthetic toxic-ity occurred in the O group.Conclusion:Pioid-free anesthesia is safe and effective in modified radical mastectomy for breast cancer,shortening recovery time,time to first flatus,and time to ambulation,while alleviating postoperative pain,systemic inflammatory response,perioperative hemodynamic fluctuations,and the incidence of postoperative nau-sea and vomiting.

Objective:To analyze the thematic distribution characteristics and evolution trends of the compensation mechanism reform policies for public hospitals in China since the new healthcare reform,and to provide references for correctly understanding the basic connotation and extension of the reform of compensation mechanism.Methods:A total of 75 documents issued at the national level were collected.The BERTopic topic model was used for thematic identification.The dynamic topic modeling method of BERTopic was adopted to conduct policy evolution analysis.Result:Since the new medical reform,the reform policy of compensation mechanism in public hospitals can be divided into eight themes,such as strengthening the operation management of public hospitals and adjusting the price of medical services.It shows an evolutionary trend of emphasizing the control of excessive growth of medical expenses and the implementation of government investment responsibilities in the early stage,focusing on the elimination of drug additions and the adjustment of medical service prices in the middle stage,and strengthening the reform of medical insurance payment methods in the later stage.Conclusions:The reform of the compensation mechanism for public hospitals is essentially a systematic reconstruction of the operation mechanism of public hospitals.Adjusting and optimizing medical service prices and reforming the medical insurance payment method are the key and focus of improving the compensation mechanism for public hospitals.

Objective To investigate the clinical prognosis of untreated residual coronary artery dissection treated with drug coated balloon(DCB).Methods A retrospective analysis was conducted on the clinical and imaging data of patients with primary coronary artery lesions(2.5-4.0 mm)treated with DCB under angiography guidance at Xuzhou Cancer Hospital,Xuzhou New Health Geriatric Hospital,and Peixian Guotai Hospital from September 2017 to April 2023.According to the observation of coronary artery dissection through angiography,the patients were divided into a dissection group and a non dissection group.The main endpoint of this study was the major adverse cardiovascular event(MACE)during a 12-month follow-up.Results A total of 381 patients were enrolled in the three research centers,with 30 cases(30 lesions)in the dissection group and 351 cases(367 lesions)in the non dissection group.There was no significant difference between the two groups in terms of age,gender,hypertension,hyperlipidemia,diabetes,smoking,previous myocardial infarction,previous percutaneous coronary intervention,coronary artery bypass grafting and other baseline clinical characteristics(all P＞0.05).Except for the reference vessel diameter(P=0.049)and DCB pressure(P=0.032),there was no statistically significant difference in the characteristics of coronary angiography lesions between the two groups of patients(both P＞0.05).During a 12-month follow-up,there was no statistically significant difference(P＞0.05)in the incidence of MACE between the dissection group and the non dissection group after DCB treatment for primary coronary artery lesions in situ.Conclusions Untreated residual dissection after DCB treatment of de novo coronary lesions does not lead to an increase in clinical MACE.