Objective:To evaluate the role of meningeal γδ T cell-derived interleukin-17A (IL-17A) in postoperative cognitive dysfunction (POCD) in aged mice.Methods:Forty healthy male C57BL/6N mice, aged 18 months, weighing 30-40 g, were divided into 4 groups ( n=10 each) using a table of random numbers: control group (group C), anti-γδ T cell receptor antibody (Anti-TCR γδ) group, POCD group (group P), and POCD+ Anti-TCR γδ group (group P+ Anti-TCR γδ). Anesthesia was induced with 8% sevoflurane and maintained with 3% sevoflurane, and the internal fixation for tibial fracture was performed to establish the mouse model of POCD in P and P+ Anti-TCR γδ groups. Anti-TCR γδ antibody 2.5 μg was infused into the occipital cistern on postoperative day 4 in P+ Anti-TCR γδ and Anti-TCR γδ groups. The open field test, novel object recognition test and Y-maze test were conducted sequentially at 7th day after surgery. The total distance traveled in the open field and the number of entries into the central area were recorded, and the novel object recognition index and preference index for exploring the novel arm were calculated. The mice were sacrificed at the end of the behavioral testing, the meninges were obtained for detection of the expression of IL-17A in γδ T cells by flow cytometry, and the hippocampal tissues were harvested for determination of the expression of vesicular glutamate transporter1 (VGLUT1), glutamate receptor 1 (GluR1), and IL-17A receptor (IL-17AR) (by Western blot). Results:There was no statistically significant difference in the total distance traveled in the open field test or the number of entries into the central area among the four groups ( P>0.05). Compared with group C, the novel object recognition index and preference index for novel arm exploration were significantly decreased, the expression of meningeal γδ T cells and IL-17AR in hippocampal tissues was up-regulated, and the expression of VGLUT1 and GluR1 was down-regulated in group P and group P+ Anti-TCR γδ ( P<0.05), and no significant change was found in the aforementioned parameters in group Anti-TCR γδ ( P>0.05). Compared with group P, the novel object recognition index and preference index for novel arm exploration were significantly increased, the expression of meningeal γδ T cells and IL-17AR was down-regulated, and the expression of VGLUT1 and GluR1 was up-regulated in group P+ Anti-TCR γδ ( P<0.05). Conclusions:Increased meningeal γδ T cell-derived IL-17A can up-regulate the expression of IL17AR in the hippocampus and down-regulate the expression of VGLUT1 and GluR1, thus involving in the development of POCD in aged mice.

Objective To evaluate the diagnostic value of prostate health index(PHI)and prostate health index density(PHID)in identifying intermediate-to high-risk prostate cancer(PCa).Methods Clinical data of 160 treatment-na?ve patients with highly suspected PCa,who underwent initial prostate biopsy in our hospital during Jul.2022 and Feb.2024,were retrospectively analyzed.Data included age,body mass index(BMI),prostate volume(PV),total prostate-specific antigen(tPSA),free PSA(fPSA),[-2]proPSA(p2PSA),PHI and PHID.Biopsy-positive results were stratified according to the EAU D'Amico risk criteria.Receiver operating characteristic(ROC)curve and multivariate logistic regression analysis were employed to assess the diagnostic performance of PHI and PHID in predicting PCa and identifying intermediate-to high-risk PCa.Results There were statistically significant differences in tPSA,p2PSA,PHI and PHID between the negative and positive groups,as well as among the low-,medium-and high-risk groups(P＜0.01).Both PHI and PHID demonstrated good diagnostic performance in predicting PCa(AUC=0.820 8 and 0.875 7,respectively;all P＜0.001),and in identifying intermediate-to high-risk PCa(AUC=0.838 0 and 0.878 3,respectively;all P＜0.001).Compared to the baseline model,the incorporation of PHI and PHID individually into the multivariate model significantly improved the screening performance for PCa(AUC=0.910 and 0.898,respectively;all P＜0.001).Conclusion PHI and PHID exhibit high diagnostic efficacy in screening PCa,particularly in identifying intermediate-to high-risk disease.

Objective To explore the differences between community-based population-wide early screening combined with two-way referral model and the traditional opportunistic screening model for early diagnosis of early-stage prostate cancer.Methods From August 2022 to April 2024,12815high-risk elderly males within the Fifth People's Hospital of Shanghai,Fudan University healthcare al-liance underwent population-wide prostate-specific antigen(PSA)screening across five community health centers.Among them,1005 cases with PSA＞4.0ng/ml were identified and referred via a two-way referral model to the Fifth People's Hospital of Shanghai,Fudan University for further evaluation.Prostate biopsies were performed on 445 eligible patients who consented(mean age was 65.6±6.8 years),and clinical data were collected as the community-based population-wide early screening combined with two-way referral mod-el group(Group A).During the same period,4600high-risk elderly males with lower urinary tract symptoms underwent opportunistic PSA screening at the Fifth People's Hospital of Shanghai,Fudan University identifying 700 cases with abnormal PSA levels.Biopsies were performed on 270 eligible patients who consented(mean age was 64.8±6.4 years),and clinical data were collected as the traditional op-portunistic screening model group(Group B).Baseline characteristics,positive rate of prostate cancer,clinical stages,and pathological grades were compared between the two groups.Results There were no statistically significant differences in age,PSA levels,family his-tory,body mass index(BMI),marital status and education level between the groups.There were 160 positive cases in Group A,the pos-itive rate was 35.9％,while there were 90 positive cases in Group B,the positive rate was 33.3％,with no significant statistical differ-ence(P=0.652).In Group A,100 cases(62.5％of diagnosed cases)were classified as clinical stage ≤T2N0M0,compared to 35 ca-ses(38.9％)in Group B,showing a significant statistical difference(P=0.023).Group A had 105 cases(65.6％of diagnosed cases)with International Society of Urological Pathology(ISUP)grade ≤3,while Group B had 30 cases(33.3％),showing a significant statis-tical difference(P=0.002).Conclusion Community-based population-wide early screening combined with two-way referral model showed no difference in the positive rate of prostate cancer compared to traditional opportunistic screening but exhibited advantages in diag-nosing early-stage prostate cancer.Wider adoption of this model may improve the current status of delayed staging and poor prognosis a-mong prostate cancer patients in China.

Objective:To evaluate the effect of short-chain fatty acid(SCFA) on perioperative cognitive dysfunction in aged rats through mitogen-activated protein kinase p38(p38 MAPK)/nuclear factor-κB p65(NF-κB p65) pathway.Methods:According to random number table method, 32 healthy SPF-grade male SD rats, aged 16 months and weighing 520~620 g, were divided into control group, short-chain fatty acid group (SCFA group), perioperative cognitive dysfunction group (PCD group) and perioperative cognitive dysfunction+ short-chain fatty acid group (SCFA+ PCD group), with 8 rats in each group. The perioperative cognitive dysfunction model was established by sevoflurane anesthesia plus internal fixation of tibial fractures. Rats in SCFA group and SCFA+ PCD group freely drank water added with SCFA for 28 days. On the 29th day, rats in SCFA+ FCD group underwent tibial fracture internal fixation surgery. Morris water maze test was performed on the 7th day after surgery to evaluate the cognitive function of rats. The Nissl bodies of hippocampus were observed by Nissl's staining. The hippocampus tissue was collected to analyze the expressions of interleukin-1β (IL-1β), interleukin-6 (IL-6), p38 MAPK, phosphorylated p38 MAPK, NF-κB p65 and phosphorylated NF-κB p65 by Western blot.The SPSS 27.0 software was used for statistical analysis. One-way ANOVA was used for comparison among multiple groups, and LSD- t test was used for further pairwise comparison. Results:(1) The results of Morris water maze test showed that the times of crossing the original platform, the escape latency and the residence time in the original platform quadrant were statistically significant among the four groups on the 7th day after surgery ( F=13.80, 47.80, 6.46, all P<0.05). The escape latencies of the SCFA+ PCD group and PCD group were both longer than that in the control group (both P<0.05). The times of crossing the original platform in SCFA+ PCD group and PCD group were less than that of control group (both P<0.05). The residence time in the original platform quadrant in SCFA+ PCD group and PCD group was shorter than that of control group (both P<0.05).Compared with PCD group, the escape latency was shorter, the times of crossing the original platform were more and the residence time in the original platform quadrant was longer in SCFA+ PCD group (all P<0.05). (2) The expression levels of IL-1β, IL-6, phosphorylated p38 MAPK and phosphorylated NF-κB p65 were statistically significant among the four groups ( F=184.28, 139.27, 19.40, 58.47, all P<0.05). The expression levels of IL-1β, IL-6, phosphorylated p38 MAPK and phosphorylated NF-κB p65 were higher in SCFA+ PCD group (0.49±0.10, 0.60±0.05, 0.489±0.012, 0.435±0.005) and PCD group (0.85±0.05, 1.12±0.08, 0.519±0.028, 0.473±0.008) than those in control group (0.13±0.02, 0.42±0.10, 0.437±0.010, 0.362±0.013)(all P<0.05). The expression levels of IL-1β, IL-6, phosphorylated p38 MAPK and phosphorylated NF-κB p65 were lower in SCFA+ PCD group than PCD group (all P<0.05). (3) The average gray value of Nissl bodies was statistically significant different among the four groups ( F=14.65, P<0.05). The average gray value of Nissl bodies was lower in SCFA+ PCD group (193.2±8.1) and PCD group (160.5±14.1) than that of control group (221.2±14.8) (both P<0.05). The average gray value of Nissl bodies was higher in SCFA+ PCD group than that in PCD group( P<0.05). Conclusion:Short-chain fatty acid attenuates cognitive dysfunction, which may be related with inhibiting p38 MAPK/NF-κB p65 pathway and reducing the neuroinflammation.

Objective:To evaluate the effect of short-chain fatty acid(SCFA) on perioperative cognitive dysfunction in aged rats through mitogen-activated protein kinase p38(p38 MAPK)/nuclear factor-κB p65(NF-κB p65) pathway.Methods:According to random number table method, 32 healthy SPF-grade male SD rats, aged 16 months and weighing 520~620 g, were divided into control group, short-chain fatty acid group (SCFA group), perioperative cognitive dysfunction group (PCD group) and perioperative cognitive dysfunction+ short-chain fatty acid group (SCFA+ PCD group), with 8 rats in each group. The perioperative cognitive dysfunction model was established by sevoflurane anesthesia plus internal fixation of tibial fractures. Rats in SCFA group and SCFA+ PCD group freely drank water added with SCFA for 28 days. On the 29th day, rats in SCFA+ FCD group underwent tibial fracture internal fixation surgery. Morris water maze test was performed on the 7th day after surgery to evaluate the cognitive function of rats. The Nissl bodies of hippocampus were observed by Nissl's staining. The hippocampus tissue was collected to analyze the expressions of interleukin-1β (IL-1β), interleukin-6 (IL-6), p38 MAPK, phosphorylated p38 MAPK, NF-κB p65 and phosphorylated NF-κB p65 by Western blot.The SPSS 27.0 software was used for statistical analysis. One-way ANOVA was used for comparison among multiple groups, and LSD- t test was used for further pairwise comparison. Results:(1) The results of Morris water maze test showed that the times of crossing the original platform, the escape latency and the residence time in the original platform quadrant were statistically significant among the four groups on the 7th day after surgery ( F=13.80, 47.80, 6.46, all P<0.05). The escape latencies of the SCFA+ PCD group and PCD group were both longer than that in the control group (both P<0.05). The times of crossing the original platform in SCFA+ PCD group and PCD group were less than that of control group (both P<0.05). The residence time in the original platform quadrant in SCFA+ PCD group and PCD group was shorter than that of control group (both P<0.05).Compared with PCD group, the escape latency was shorter, the times of crossing the original platform were more and the residence time in the original platform quadrant was longer in SCFA+ PCD group (all P<0.05). (2) The expression levels of IL-1β, IL-6, phosphorylated p38 MAPK and phosphorylated NF-κB p65 were statistically significant among the four groups ( F=184.28, 139.27, 19.40, 58.47, all P<0.05). The expression levels of IL-1β, IL-6, phosphorylated p38 MAPK and phosphorylated NF-κB p65 were higher in SCFA+ PCD group (0.49±0.10, 0.60±0.05, 0.489±0.012, 0.435±0.005) and PCD group (0.85±0.05, 1.12±0.08, 0.519±0.028, 0.473±0.008) than those in control group (0.13±0.02, 0.42±0.10, 0.437±0.010, 0.362±0.013)(all P<0.05). The expression levels of IL-1β, IL-6, phosphorylated p38 MAPK and phosphorylated NF-κB p65 were lower in SCFA+ PCD group than PCD group (all P<0.05). (3) The average gray value of Nissl bodies was statistically significant different among the four groups ( F=14.65, P<0.05). The average gray value of Nissl bodies was lower in SCFA+ PCD group (193.2±8.1) and PCD group (160.5±14.1) than that of control group (221.2±14.8) (both P<0.05). The average gray value of Nissl bodies was higher in SCFA+ PCD group than that in PCD group( P<0.05). Conclusion:Short-chain fatty acid attenuates cognitive dysfunction, which may be related with inhibiting p38 MAPK/NF-κB p65 pathway and reducing the neuroinflammation.

Objective:To evaluate the role of meningeal γδ T cell-derived interleukin-17A (IL-17A) in postoperative cognitive dysfunction (POCD) in aged mice.Methods:Forty healthy male C57BL/6N mice, aged 18 months, weighing 30-40 g, were divided into 4 groups ( n=10 each) using a table of random numbers: control group (group C), anti-γδ T cell receptor antibody (Anti-TCR γδ) group, POCD group (group P), and POCD+ Anti-TCR γδ group (group P+ Anti-TCR γδ). Anesthesia was induced with 8% sevoflurane and maintained with 3% sevoflurane, and the internal fixation for tibial fracture was performed to establish the mouse model of POCD in P and P+ Anti-TCR γδ groups. Anti-TCR γδ antibody 2.5 μg was infused into the occipital cistern on postoperative day 4 in P+ Anti-TCR γδ and Anti-TCR γδ groups. The open field test, novel object recognition test and Y-maze test were conducted sequentially at 7th day after surgery. The total distance traveled in the open field and the number of entries into the central area were recorded, and the novel object recognition index and preference index for exploring the novel arm were calculated. The mice were sacrificed at the end of the behavioral testing, the meninges were obtained for detection of the expression of IL-17A in γδ T cells by flow cytometry, and the hippocampal tissues were harvested for determination of the expression of vesicular glutamate transporter1 (VGLUT1), glutamate receptor 1 (GluR1), and IL-17A receptor (IL-17AR) (by Western blot). Results:There was no statistically significant difference in the total distance traveled in the open field test or the number of entries into the central area among the four groups ( P>0.05). Compared with group C, the novel object recognition index and preference index for novel arm exploration were significantly decreased, the expression of meningeal γδ T cells and IL-17AR in hippocampal tissues was up-regulated, and the expression of VGLUT1 and GluR1 was down-regulated in group P and group P+ Anti-TCR γδ ( P<0.05), and no significant change was found in the aforementioned parameters in group Anti-TCR γδ ( P>0.05). Compared with group P, the novel object recognition index and preference index for novel arm exploration were significantly increased, the expression of meningeal γδ T cells and IL-17AR was down-regulated, and the expression of VGLUT1 and GluR1 was up-regulated in group P+ Anti-TCR γδ ( P<0.05). Conclusions:Increased meningeal γδ T cell-derived IL-17A can up-regulate the expression of IL17AR in the hippocampus and down-regulate the expression of VGLUT1 and GluR1, thus involving in the development of POCD in aged mice.

Objective To evaluate the diagnostic value of prostate health index(PHI)and prostate health index density(PHID)in identifying intermediate-to high-risk prostate cancer(PCa).Methods Clinical data of 160 treatment-na?ve patients with highly suspected PCa,who underwent initial prostate biopsy in our hospital during Jul.2022 and Feb.2024,were retrospectively analyzed.Data included age,body mass index(BMI),prostate volume(PV),total prostate-specific antigen(tPSA),free PSA(fPSA),[-2]proPSA(p2PSA),PHI and PHID.Biopsy-positive results were stratified according to the EAU D'Amico risk criteria.Receiver operating characteristic(ROC)curve and multivariate logistic regression analysis were employed to assess the diagnostic performance of PHI and PHID in predicting PCa and identifying intermediate-to high-risk PCa.Results There were statistically significant differences in tPSA,p2PSA,PHI and PHID between the negative and positive groups,as well as among the low-,medium-and high-risk groups(P＜0.01).Both PHI and PHID demonstrated good diagnostic performance in predicting PCa(AUC=0.820 8 and 0.875 7,respectively;all P＜0.001),and in identifying intermediate-to high-risk PCa(AUC=0.838 0 and 0.878 3,respectively;all P＜0.001).Compared to the baseline model,the incorporation of PHI and PHID individually into the multivariate model significantly improved the screening performance for PCa(AUC=0.910 and 0.898,respectively;all P＜0.001).Conclusion PHI and PHID exhibit high diagnostic efficacy in screening PCa,particularly in identifying intermediate-to high-risk disease.

Objective To explore the differences between community-based population-wide early screening combined with two-way referral model and the traditional opportunistic screening model for early diagnosis of early-stage prostate cancer.Methods From August 2022 to April 2024,12815high-risk elderly males within the Fifth People's Hospital of Shanghai,Fudan University healthcare al-liance underwent population-wide prostate-specific antigen(PSA)screening across five community health centers.Among them,1005 cases with PSA＞4.0ng/ml were identified and referred via a two-way referral model to the Fifth People's Hospital of Shanghai,Fudan University for further evaluation.Prostate biopsies were performed on 445 eligible patients who consented(mean age was 65.6±6.8 years),and clinical data were collected as the community-based population-wide early screening combined with two-way referral mod-el group(Group A).During the same period,4600high-risk elderly males with lower urinary tract symptoms underwent opportunistic PSA screening at the Fifth People's Hospital of Shanghai,Fudan University identifying 700 cases with abnormal PSA levels.Biopsies were performed on 270 eligible patients who consented(mean age was 64.8±6.4 years),and clinical data were collected as the traditional op-portunistic screening model group(Group B).Baseline characteristics,positive rate of prostate cancer,clinical stages,and pathological grades were compared between the two groups.Results There were no statistically significant differences in age,PSA levels,family his-tory,body mass index(BMI),marital status and education level between the groups.There were 160 positive cases in Group A,the pos-itive rate was 35.9％,while there were 90 positive cases in Group B,the positive rate was 33.3％,with no significant statistical differ-ence(P=0.652).In Group A,100 cases(62.5％of diagnosed cases)were classified as clinical stage ≤T2N0M0,compared to 35 ca-ses(38.9％)in Group B,showing a significant statistical difference(P=0.023).Group A had 105 cases(65.6％of diagnosed cases)with International Society of Urological Pathology(ISUP)grade ≤3,while Group B had 30 cases(33.3％),showing a significant statis-tical difference(P=0.002).Conclusion Community-based population-wide early screening combined with two-way referral model showed no difference in the positive rate of prostate cancer compared to traditional opportunistic screening but exhibited advantages in diag-nosing early-stage prostate cancer.Wider adoption of this model may improve the current status of delayed staging and poor prognosis a-mong prostate cancer patients in China.

Objective:To evaluate the effect of short-chain fatty acids on microglial synapse engulfment in aged rats with postoperative cognitive dysfunction (POCD).Methods:Forty-eight healthy male Sprague-Dawley rats, aged 18 months, weighing 520-650 g, were divided into 4 groups ( n=12 each) using a random number table method: control group (group C), short-chain fatty acids group (group S), POCD group (group P), and POCD+ short-chain fatty acids group (group PS). Rats received short-chain fatty acids (sodium propionate 25.9 mmol/L, sodium butyrate 40 mmol/L and sodium acetate 67.5 mmol/L) in the free drinking water for 28 days in S and PS groups. On day 29, anesthesia was induced with 4%-5% sevoflurane and maintained with 3% sevoflurane, and the tibial fracture internal fixation was performed to prepare a rat model of POCD in P group and PS group. Morris water maze test was performed at day 7 after surgery. The escape latency, times of crossing the original platform, mean swimming speed and time spent in the original platform quadrant were recorded. The rats were sacrificed at the end of Morris water maze test, and the brains were collected to analyze the number and density of dendritic spines in the hippocampal CA1 region (by Golgi staining) and to determine the expression of postsynaptic density 95 (PSD95) and complement 1q (C1q) in the hippocampal CA1 region (by immunofluorescence). Results:Compared with group C, the times of crossing the original platform were significantly decreased, the time spent in the original platform quadrant was shortened, the escape latency was prolonged, the number and density of dendritic spines and the number of intersection points between dendrites and concentric circles were decreased, the expression of PSD95 was down-regulated, and the expression of C1q was up-regulated in P and PS groups ( P<0.05). Compared with group P, the times of crossing the original platform were significantly increased, the time spent in the original platform quadrant was prolonged, the escape latency was shortened, the number and density of dendritic spines and the number of intersection points between dendrites and concentric circles were increased, the expression of PSD-95 was up-regulated, and the expression of C1q was down-regulated in group PS ( P<0.05). Conclusions:The mechanism by which short-chain fatty acids attenuates POCD is related to decreased microglial engulfment of synapses in aged rats.

Objective To evaluate the clinical efficacy of infliximab (IFX) in Crohn′s disease (CD) and its effects on mucosal healing and promoting fistula closure.Methods Between September 2007 and February 2011,relevant clinical data of CD patients treated with IFX in the Department of Gastroenterology,Ruijin Hospital were collected and the efficacy and safety of IFX were retrospectively analyzed.After IFX therapy,the efficacy evaluation included laboratory index,clinical efficacy,efficacy of fistula closure and mucosal healing.The data were analyzed using t test and Wilcoxon signed-rank test.Results A total of 22 patients were enrolled in this study,11 males and 11 females; the mean age was 29.3 years.The dosage of IFX was 5 mg/kg to 10 mg/kg at week 0,2,6to induce remission,and every 8 weeks on maintenance therapy.Of 22 patients,16 patients were active CD.One case dropped out.At week 14,of the remaining 15 cases,11 cases achieved clinical remission,two cases achieved clinically effective and two cases were ineffective.Crohn′s disease activity index (CDAI) (112±80) and ESR [(13±11) mm/1 h] of week 14 decreased compared with that of week 0 [(186±88),(21± 15) mm/1 h,P=0.04 and 0.007].Two cases of 10 patients with fistula dropped out as a result of ineffective,while eight cases had a partial response and six patients sustained response during the maintenance therapy,but no fistula closed and completely disappear.Seven patients reviewed by endoscopy after five times IFX therapy (24 weeks),after therapy the simple endoscopic score for Crohn′ s disease (SES-CD) ( 3.21 ± 2.89 ) decreased compared with that before treatment (5.86±3.02) (Z＝-2.38,P＝0.018).Eleven times of adverse events were found in nine patients,infusion reaction and respiratory tract infection were more common and no severe adverse effect was observed.Conclusions IFX can rapidly improve clinical symptoms and with good safety.The effects in mucosal healing and fistula closure may occur at early medication.