Curzerene, a sesquiterpene compound isolated from Curcuma Radix, exhibits various therapeutic effects, such as anti-tumor and anti-hyperlipidemic properties. However, its neuroprotective effects have not yet been reported. This study focused on exploring the neuroprotective effect of curzerene and elucidating its potential mechanism by combining molecular biotechnology with multi-omics approaches. Curzerene was orally administered to LPS-induced depressive-like behaviors and cognitive impairment in mice for 14 days, and the related biochemical parameters were evaluated. The possible mechanisms were elucidated using qRT-PCR, Western Blot, immunofluorescence, untargeted metabolomics, GC-MS and 16S rDNA comprehensively. Curzerene ameliorated depression symptoms and cognitive impairment by increasing the preference for sucrose in SPT and the central area and total distance traveled in OFT, reducing the immobility time in TST and FST, as well as rising the spontaneous alternation ratio in Y maze. Multiple molecular biology techniques analyses indicated the ameliorative effect of curzerene via HMGB1/RAGE/ TLR4 pathway. Moreover, curzerene primarily regulates purine metabolism, phenylalanine, tyrosine and tryptophan biosynthesis, phenylalanine metabolism, pyrimidine metabolism, etc. Furthermore, intervention increased the relative abundance of Parabacteroides, Clostridia_UCG-014_unclassified, and Rhodospirillales_unclassified, and enhanced the production of SCFAs. This work demonstrated that curzerene effectively protects against LPS-induced neurological damage, potentially by inhibiting the HMGB1/ RAGE/TLR4 pathway through the restoration of gut microbiota homeostasis, modulation of metabolites, and enhancement of SCFAs. In conclusion, this study offers new perspectives on the therapeutic possibilities of curzerene in mitigating depressive-like behaviors and cognitive impairment.

OBJECTIVE To conduct a literature review of one case of follicular lymphoma complicated with iliac bone Cryptococcus neoformans infection so as to raise the understanding of such pathogen in the field of HIV-negative Hodgkin's/non-Hodgkin's lymphoma.METHODS The clinical data were collected from one case of follicular lymphoma patient complicated with C.neoformans infection who was treated in Xinrui Hospital of Xin-wu District,Wuxi City on Feb.24,2023 and retrospectively analyzed.All of relevant literatures regarding to the subject were retrieved in Pubmed,CNKI,Wanfang and VIP databases,and the clinical data of the patients with HIV-negative Hodgkin's/non-Hodgkin's lymphoma with C.neoformans infection were screened out and summa-rized.RESULTS The case was a 28-year-old male and had the underlying disease of follicular lymphoma.The C.neoformans was detected by iliac bone histopathology and metagenome next generation sequencing(mNGS).The condition of the patient improved after the treatment with amphotericin B cholesterol sulphate com-pound and fluconazole.A total of 28 patients,with this case included,were involved in the literature review,23 of whom were male,and 5 were female,and the age ranged between 16 and 79 years old.With respect to major in-fection sites,there were 15(53.57％)cases of cerebral infection,9(32.14％)cases of blood infections,7(25.00％)cases of pulmonary infection,4(14.285％)cases of skin infections,2(7.14％)cases of muscle tis-sue infections,2(7.14％)cases of pleural effusion infections,2(7.14％)cases of bone infections and 1(3.57％)case of bone marrow infection.Totally 11 patients had disseminated Cryptococcus infection,accounting for 39.28％.CONCLUSIONS The C.neoformans infection is seldom detected in the patients with HIV-negative Hodgkin's/non-Hodgkin's lymphoma.The brain is the major infection site with the high probability of dissemina-ted infection.It is necessary for the hospital to deepen the understanding of the pathogen in the field of HIV-negative Hodgkin's/non-Hodgkin's lymphoma.

Objective To investigate the influencing factors related to the severity of tinnitus with normal hearing and to provide a clinical basis for the treatment of such patients.Methods From November 2019 to May 2020,150 normal hearing patients with tinnitus as their first chief complain in the outpatient clinic of our center were selected.The severity of tinnitus was assessed by the tinnitus handicap inventory(THI),and the quality of sleep and psychological condition were assessed by the Pittsburgh sleep quality index inventory(PSQI)and the anxie-ty and depression scale(HADS).The relationship between tinnitus severity and patients'gender,age,duration of illness,tinnitus side,tinnitus dominant sound frequency,tinnitus dominant sound loudness,sleep quality,anxiety and depression were analyzed using Pearson's method and Logistic multi-factor regression.Results The Pearson correlation analysis suggested that sleep quality(r=0.667,P＜0.001),anxiety status(r=0.603,P＜0.001)and depression status(r=0.593,P＜0.001)were correlated with the THI classification,and patients with poorer sleep quality and higher anxiety and depression scores had more severe tinnitus.Logistic multi-factor regression analysis showed that only sleep quality had a significant effect on THI classification(P＜0.001).Conclusion Sleep quality may be related to the severity of tinnitus patients with normal hearing,and it is important to focus on their sleep sta-tus in the clinical management of such patients.

Objective:To elucidate the temporal characteristics of dysphagia following infratentorial stroke and its associa-tion with penetration/aspiration.Method:A total of 51 patients with infratentorial stroke and 26 healthy controls were recruited.All partici-pants underwent videofluoroscopic swallowing studies(VFSS),during which they swallowed 5ml of thin liquid in two separate trials.Swallowing parameters analyzed included oral transit time(OTT),velopharyngeal clo-sure duration(VCD),hyoid movement duration(HMD),laryngeal vestibule closure duration(LCD),upper esophageal sphincter(UES)opening duration(UOD),and stage transition duration(STD).The temporal coor-dination and sequential order of four swallowing actions and the intervals namely T1-T4 were also assessed.Inter-rater variability was evaluated using intraclass correlation coefficients(ICCs)for 20％of the results.Result:In the patient group,40.2％exhibited failed opening in UES,39.3％had penetration,and 20.5％ex-perienced aspiration.Compared to the control group,patients showed significantly prolonged OTT,VCD,and STD(P＜0.01),while UOD was significantly shorter(P＜0.01).The conformity rates of temporal sequences 3 and 4 were significantly lower in the patient group compared to controls(P＜0.001),and intervals Tl,T2,and T3 were significantly longer(P＜0.01).Significant negative correlations were found between VCD and PAS,UOD and PAS,and T2(P＜0.01).All measured parameters demonstrated good reliability.Conclusion:Patients with infratentorial stroke experience abnormal swallowing sequence,which is associated with the severity of penetration and aspiration.These findings may help in developing more targeted interven-tions to prevent aspiration.

Objective:To evaluate the accuracy of the oral healthcare information provided by different large language models (LLM) to explore their feasibility and limitations in the application of oral auxiliary, treatment and health consultation.Methods:This study designed eight items comprising 47 questions in total related to the diagnosis and treatment of oral diseases [to assess the performance of LLM as an artificial intelligence (AI) medical assistant], and five items comprising 35 questions in total about oral health consultations (to assess the performance of LLM as a simulated doctor). These questions were answered individually by the five LLM models (Erine Bot, HuatuoGPT, Tongyi Qianwen, iFlytek Spark, ChatGPT). Two attending physicians with more than 5 years of experience independently rated the responses using the 3C criteria (correct, clear, concise), and the consistency between the raters was assessed using the Spearman rank correlation coefficient, and the Kruskal-Wallis test and Dunn post hoc test were used to assess the statistical differences between the models. Additionally, this study used 600 questions from the 2023 dental licensing examination to evaluate the time taken to answer, scores, and accuracy of each model.Results:As an AI medical assistant, LLM can assist doctors in diagnosis and treatment decision-making, with an inter-evaluator Spearman coefficient of 0.505 ( P<0.01). As a simulated doctor, LLM can carry out patient popularization, with an inter-evaluator Spearman coefficient of 0.533 ( P<0.01). The 3C scores of each model as an AI medical assistant and a simulated doctor were respectively: 2.00 (1.00, 3.00) and 2.00 (2.00, 3.00) points of Erine Bot, 1.00 (1.00, 2.00) and 2.00 (1.00, 2.00) points of HuatuoGPT, 2.00 (1.00, 2.00) and 2.00 (1.00, 3.00) points of Tongyi Qianwen, 2.00 (1.00, 2.00) and 2.00 (1.75, 2.25) points of iFlytek Spark, 3.00 (2.00, 3.00) and 3.00 (2.00, 3.00) points of ChatGPT (full score of 4 points). The Kruskal-Wallis test results showed that, as an AI medical assistant or a simulated doctor, there were statistically differences in the 3C scores among the five large language models (all P<0.001). The average score of the 5 LLMs on the dental licensing examination was 370.2, with an accuracy rate of 61.7% (370.2/600) and a time consumption of 94.6 min. Specifically, Erine Bot took 115 min, scored 363 points with an accuracy rate of 60.5% (363/600), HuatuoGPT took 224 min and scored 305 points with an accuracy rate of 50.8% (305/600), Tongyi Qianwen took 43 min, scored 438 points with an accuracy rate of 73.0% (438/600), iFlytek Spark took 32 min, scored 364 points with an accuracy rate of 60.7% (364/600), and ChatGPT took 59 min, scored 381 points with an accuracy rate of 63.5% (381/600). Conclusions:Based on the evaluation of LLM′s dual roles as an AI medical assistant and a simulated doctor, ChatGPT performes the best, with basically correct, clear and concise answers, followed by Erine Bot, Tongyi Qianwen and iFlytek Spark, with HuatuoGPT lagging behind significantly. In the dental licensing examination, all the 4 LLM, except for HuatuoGPT, reach the passing level, and the time consumpution for answering is significantly reduced compared to the 8 h required for the exam regulations in all of the five models. LLM has the feasibility of application in oral auxiliary, treatment and health consultation, and it can help both doctors and patients obtain medical information quickly. Howere, their outputs carry a risk of errors (since the 3C scoring results do not reach the full marks), so prudent judgment should be exercised when using them.

Objective To investigate the influencing factors related to the severity of tinnitus with normal hearing and to provide a clinical basis for the treatment of such patients.Methods From November 2019 to May 2020,150 normal hearing patients with tinnitus as their first chief complain in the outpatient clinic of our center were selected.The severity of tinnitus was assessed by the tinnitus handicap inventory(THI),and the quality of sleep and psychological condition were assessed by the Pittsburgh sleep quality index inventory(PSQI)and the anxie-ty and depression scale(HADS).The relationship between tinnitus severity and patients'gender,age,duration of illness,tinnitus side,tinnitus dominant sound frequency,tinnitus dominant sound loudness,sleep quality,anxiety and depression were analyzed using Pearson's method and Logistic multi-factor regression.Results The Pearson correlation analysis suggested that sleep quality(r=0.667,P＜0.001),anxiety status(r=0.603,P＜0.001)and depression status(r=0.593,P＜0.001)were correlated with the THI classification,and patients with poorer sleep quality and higher anxiety and depression scores had more severe tinnitus.Logistic multi-factor regression analysis showed that only sleep quality had a significant effect on THI classification(P＜0.001).Conclusion Sleep quality may be related to the severity of tinnitus patients with normal hearing,and it is important to focus on their sleep sta-tus in the clinical management of such patients.

Objective:To elucidate the temporal characteristics of dysphagia following infratentorial stroke and its associa-tion with penetration/aspiration.Method:A total of 51 patients with infratentorial stroke and 26 healthy controls were recruited.All partici-pants underwent videofluoroscopic swallowing studies(VFSS),during which they swallowed 5ml of thin liquid in two separate trials.Swallowing parameters analyzed included oral transit time(OTT),velopharyngeal clo-sure duration(VCD),hyoid movement duration(HMD),laryngeal vestibule closure duration(LCD),upper esophageal sphincter(UES)opening duration(UOD),and stage transition duration(STD).The temporal coor-dination and sequential order of four swallowing actions and the intervals namely T1-T4 were also assessed.Inter-rater variability was evaluated using intraclass correlation coefficients(ICCs)for 20％of the results.Result:In the patient group,40.2％exhibited failed opening in UES,39.3％had penetration,and 20.5％ex-perienced aspiration.Compared to the control group,patients showed significantly prolonged OTT,VCD,and STD(P＜0.01),while UOD was significantly shorter(P＜0.01).The conformity rates of temporal sequences 3 and 4 were significantly lower in the patient group compared to controls(P＜0.001),and intervals Tl,T2,and T3 were significantly longer(P＜0.01).Significant negative correlations were found between VCD and PAS,UOD and PAS,and T2(P＜0.01).All measured parameters demonstrated good reliability.Conclusion:Patients with infratentorial stroke experience abnormal swallowing sequence,which is associated with the severity of penetration and aspiration.These findings may help in developing more targeted interven-tions to prevent aspiration.

Objective:To explore the safety and efficacy of intraosseous regional administration (IORA) of vancomycin for preventing infection in primary total knee arthroplasty (TKA).Methods:A total of 124 patients with knee osteoarthritis undergoing TKA between February 2024 and May 2024 at nine hospitals were enrolled. Preoperative infection prophylaxis involved either IORA (0.5 g vancomycin administered via intraosseous regional infusion before incision) or intravenous infusion (1 g vancomycin via peripheral vein). The IORA group included 15 males and 47 females with a median age of 66.5 years (range, 60.0-70.0 years), while the intravenous group included 14 males and 48 females with a median age of 66.0 years (range, 61.8-70.3 years) years. Intraoperative samples were collected including fat and synovium tissues after incision, before prosthesis placement, and after tourniquet release; distal femoral cancellous bone during femoral osteotomy; proximal tibial cancellous bone during tibial osteotomy; proximal intercondylar cancellous bone before prosthesis placement; and peripheral blood from non-infused arms at surgery initiation and after tourniquet release. Vancomycin concentrations were measured using liquid chromatography-tandem mass spectrometry. Vital sign changes were recorded from admission to 5~10 minutes post-IORA (IORA group) or post-incision (intravenous group). Follow-ups were conducted on postoperative day 1 and 3, and at 1 and 3 months, to document complications including IORA-related adverse events, periprosthetic joint infections, surgical site infections, red man syndrome, acute kidney injury, deep vein thrombosis and so on.Results:Vancomycin concentrations in bone, fat, and synovial tissue samples were significantly higher in the IORA group than in the intravenous group ( P<0.05), while vancomycin concentrations in blood samples were significantly lower in the IORA group than in the intravenous group ( P<0.05). Only 7.3%(41/558) of tissue samples in the IORA group had vancomycin concentrations below 2.0 μg/g (the minimum inhibitory concentration of vancomycin against coagulase-negative staphylococcus), compared to 59.3%(331/558) in the intravenous group (χ 2=11.285, P<0.001). In the intravenous group, 16.9%(21/124) of blood samples had vancomycin concentrations exceeding 15.0 mg/L (the threshold associated with a significantly increased risk of nephrotoxicity), while all concentrations in the IORA group were below this threshold, the difference was statistically significant (χ 2=22.943, P<0.001). There were no statistically significant difference ( P>0.05) in vital signs changes before and after vancomycin administration between the two groups. Two patients in the intravenous group experienced incision exudate, while no other related complications occurred in either group. Conclusions:Compared to the traditional intravenous infusion of 1 g vancomycin, intraosseous injection of a low dose (0.5 g) of vancomycin achieves higher local tissue concentrations in the knee joint with a lower incidence of adverse reactions and is safe for infection prophylaxis. Despite guidelines not recommending the routine use of vancomycin for preventing infection after primary TKA, intraosseous injection of 0.5 g vancomycin may be considered intraoperatively for primary TKA in the following scenarios: patients in medical institutions with a high prevalence of methicillin-resistant staphylococcus aureus (MRSA) infections, patients with potential preoperative MRSA colonization, or patients with cephalosporin allergy.

Objective:To explore the safety and efficacy of intraosseous regional administration (IORA) of vancomycin for preventing infection in primary total knee arthroplasty (TKA).Methods:A total of 124 patients with knee osteoarthritis undergoing TKA between February 2024 and May 2024 at nine hospitals were enrolled. Preoperative infection prophylaxis involved either IORA (0.5 g vancomycin administered via intraosseous regional infusion before incision) or intravenous infusion (1 g vancomycin via peripheral vein). The IORA group included 15 males and 47 females with a median age of 66.5 years (range, 60.0-70.0 years), while the intravenous group included 14 males and 48 females with a median age of 66.0 years (range, 61.8-70.3 years) years. Intraoperative samples were collected including fat and synovium tissues after incision, before prosthesis placement, and after tourniquet release; distal femoral cancellous bone during femoral osteotomy; proximal tibial cancellous bone during tibial osteotomy; proximal intercondylar cancellous bone before prosthesis placement; and peripheral blood from non-infused arms at surgery initiation and after tourniquet release. Vancomycin concentrations were measured using liquid chromatography-tandem mass spectrometry. Vital sign changes were recorded from admission to 5~10 minutes post-IORA (IORA group) or post-incision (intravenous group). Follow-ups were conducted on postoperative day 1 and 3, and at 1 and 3 months, to document complications including IORA-related adverse events, periprosthetic joint infections, surgical site infections, red man syndrome, acute kidney injury, deep vein thrombosis and so on.Results:Vancomycin concentrations in bone, fat, and synovial tissue samples were significantly higher in the IORA group than in the intravenous group ( P<0.05), while vancomycin concentrations in blood samples were significantly lower in the IORA group than in the intravenous group ( P<0.05). Only 7.3%(41/558) of tissue samples in the IORA group had vancomycin concentrations below 2.0 μg/g (the minimum inhibitory concentration of vancomycin against coagulase-negative staphylococcus), compared to 59.3%(331/558) in the intravenous group (χ 2=11.285, P<0.001). In the intravenous group, 16.9%(21/124) of blood samples had vancomycin concentrations exceeding 15.0 mg/L (the threshold associated with a significantly increased risk of nephrotoxicity), while all concentrations in the IORA group were below this threshold, the difference was statistically significant (χ 2=22.943, P<0.001). There were no statistically significant difference ( P>0.05) in vital signs changes before and after vancomycin administration between the two groups. Two patients in the intravenous group experienced incision exudate, while no other related complications occurred in either group. Conclusions:Compared to the traditional intravenous infusion of 1 g vancomycin, intraosseous injection of a low dose (0.5 g) of vancomycin achieves higher local tissue concentrations in the knee joint with a lower incidence of adverse reactions and is safe for infection prophylaxis. Despite guidelines not recommending the routine use of vancomycin for preventing infection after primary TKA, intraosseous injection of 0.5 g vancomycin may be considered intraoperatively for primary TKA in the following scenarios: patients in medical institutions with a high prevalence of methicillin-resistant staphylococcus aureus (MRSA) infections, patients with potential preoperative MRSA colonization, or patients with cephalosporin allergy.

Liver diseases are a group of complex clinical conditions caused by various factors and can lead to hepatocyte damage and liver dysfunction， posing a serious threat to human health. The cyclic GMP-AMP synthase （cGAS）-stimulator of interferon genes （STING） signaling pathway plays a key regulatory role in the course of liver diseases and is involved in the development， progression， and treatment of various diseases such as viral hepatitis， nonalcoholic fatty liver disease， liver fibrosis， and liver cancer. This article reviews the regulatory mechanisms of the cGAS-STING signaling pathway in processes such as inflammation， autophagy， antiviral response， and oxidative stress， analyzes its molecular function in liver diseases， and explores its application prospect as a potential target for the treatment of liver diseases， in order to provide a theoretical basis for developing novel therapeutic strategies for liver diseases.