Objective:To explore the effect of secreted frizzled-related protein 3 (sFRP3) on tau aggregation.Methods:(1) Twelve wild-type C57BL/6J mice and 12 P301S mutant tau transgenic (tau P301S) mice were selected; Western blotting was used to detect the sFRP3 protein expression in the brain tissues; co-immunoprecipitation experiment was conducted to verify endogenous sFRP3 binding to tau; and double immunofluorescent staining was performed to observe whether sFRP3 co-localized with phosphorylated tau. (2) Recombinant human tau (K18) and sFRP3 protein were purified, and pre-formed fibrils (PFFs) containing only K18 or mixed PFFs (containing both sFRP3 and K18) were prepared; His pull-down assay was adopted to verify exogenous purified sFRP3 binding to tau. Aggregation of these two types of PFFs was observed by thioflavin T (ThT) fluorescence,and anti-digestibility of these two types of PFFs was detected by proteinase K (PK) assay. Ultrastructure of two types of PFFs was observed under transmission electron microscope. (3) HEK293 cells stably expressing green fluorescent protein (GFP) and tau repeat domain (GFP-tau RD HEK293) were treated with the two tpyes of PFFs; intracellular tau aggregation was observed by immunofluorescence; intracellular soluble or insoluble component was evaluated by density gradient lysis. SH-SY5Y cells were treated with the two types of PFFs; cell counting kit-8 (CCK-8) assay was used to detect cell viability; Western blotting was used to detect the expressions of apoptosis-related proteins (Bcl-2-associated X protein [Bax] and cleaved caspase-3); double staining with propidium iodide (PI) and Hoechst 33342, and TUNEL were used to detect cell apoptosis. Primary neurons were treated with the two types of PFFs; density of dendritic spines was measured by 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate (DiI) staining; expressions of synaptic proteins, such as synapsin I and vesicle-associated membrane protein 2 (VAMP2), were detected by Western blotting and double immunofluorescent staining. Results:(1) sFRP3 expression in the brain tissues of tau P301S mice was significantly higher than that in wild-type mice (1.10±0.05 vs. 0.79±0.06, P<0.05). In the brain tissues of wild-type mice, endogenous sFRP3 could bind to tau, and in the brain tissues of tau P301S mice, sFRP3 and phosphorylated tau were co-localized. (2) Exogenous tau and sFRP3 could interact with each other. After constant temperature oscillation for approximately 180 minutes, the ThT fluorescent intensity in mixed PFFs was significantly higher than that in K18 PFFs. Remaining proteins of mixed PFFs were significantly increased compared with those of K18 PFFs after the same digestion time of 1 and 2 μg/mL PK (0.77±0.02 vs. 0.67±0.03; 0.52±0.04 vs. 0.33±0.02, P<0.05). The ultrastructure of mixed PFFs was longer and more compact than K18 PFFs. (3) Compared with K18 PFFs, mixed PFFs formed more intracellular tau aggregation points and had more insoluble components (insoluble protein and soluble protein ratio: 0.43±0.04 and 0.92±0.08), with significant differences ( P<0.05). Compared with K18 PFFs, mixed PFFs had significantly decreased SH-SY5Y cell viability (0.44±0.01 vs. 0.24±0.02), significantly up-regulated Bax and cleaved caspase-3 protein expressions (0.71±0.04 vs. 0.87±0.04; 0.60±0.06 vs. 0.88±0.03), significantly increased percentage of apoptotic cells (PI/Hoechst staining: 8.00%±0.49% vs. 18.11%±1.13%; TUNEL staining: 6.62%±0.91% vs. 14.94%±1.32%, P<0.05). Compared with the K18 PFFs group, the mixed PFFs group had significantly decreased density of dendritic spines ([5.7±0.28]/10 μm vs. [2.7±0.29]/10 μm), synapsin I and VAMP2 expressions (0.95±0.02 vs. 0.48±0.04; 0.88±0.03 vs. 0.52±0.06), and average fluorescent intensity of synapsin I and VAMP2 in the primary neurons (7.73±0.70 vs. 2.74±0.34; 6.14±0.60 vs. 2.96±0.54, P<0.05). Conclusion:sFRP3 interacts with tau to promote tau aggregation, and enhance the cytotoxic effect of tau aggregation.

Objective:To construct a multidisciplinary collaborative intelligent prevention and treatment system for orthopedic thrombophilia based on advanced intelligent analysis technology and to evaluate its application effectiveness in the management of orthopedic thrombophilia.Methods:Established a clinical multidisciplinary medical team guided by early warning management and human-computer interaction theory, and builded a multidisciplinary collaborative intelligent prevention and treatment system for orthopedic thrombophilia based on intelligent analysis technology.Adopting a prospective pre-and post control study method, 674 orthopedic inpatients at the Second Affiliated Hospital of Nanchang University from February 2021 to October 2022 were selected as study participants by convenient sampling method and divided into a control group (308 cases) and an observation group (366 cases) according to their admission periods. The control group underwent conventional management methods for thrombophilia. In contrast, the observation group utilized a multidisciplinary collaborative intelligent prevention and treatment system for orthopedic thrombophilia for intelligent management methods. The two groups were compared regarding risk assessment rates, assessment accuracy, assessment efficiency, dynamic assessment completion rate, knowledge awareness rates, implementation rates of multidisciplinary collaborative preventive measures, and thrombophilia incidence rates.Results:The multidisciplinary collaborative intelligent prevention and treatment system for orthopedic thrombophilia mainly included four personnel ports (doctor end, nurse end, patient or caregiver end, medical quality control end) and eight modules (patient intelligent scoring, risk grading warning, dynamic evaluation of prevention contraindications, prevention measure decision-making, health education, inpatient data monitoring, department indicator statistics, medical management). Both groups of patients completed the study. There were 238 males and 70 females in the control group, aged (42.83 ± 8.69) years old. There were 278 males and 88 females in the observation group, aged (42.35 ± 8.13) years old. The risk assessment rate, assessment accuracy rate, and dynamic assessment completion rate of the observation group for thrombophilia were 100.00% (366/366), 98.90% (362/366), and 100.00% (366/366), respectively, all higher than the control group's 94.15% (290/308), 90.58% (279/308), and 91.55% (282/308), and the differences were statistically significant ( χ2=21.99, 24.88, 32.16, all P<0.01). The knowledge awareness rate of preventing thrombophilia among high-risk patients in the observation group was 95.90% (211/220), the implementation rates of basic prevention, physical prevention, drug prevention, and combined prevention in the multidisciplinary collaborative prevention measures were 87.37% (173/198), 97.72% (215/220), 39.09% (86/220), 46.37% (102/220), and 27.73% (61/220), respectively, all higher than the control group's 85.86% (170/198), 24.74% (49/198), 30.81% (61/198), and 12.12% (24/198), and the differences were statistically significant ( χ2 values were 9.81-20.19, all P<0.05). The risk assessment time for the observation group was (3.95 ± 1.03) minutes, and the incidence of thrombophilia was 1.91% (7/366), both lower than the control group's (9.56 ± 1.65) minutes and 7.47% (23/308), with statistically significant differences ( t=53.78, χ2=6.33, both P<0.05). Conclusions:The application of the multidisciplinary collaborative intelligent prevention and treatment system for orthopedic thrombophilia has improved the implementation rate of prevention and treatment interventions by medical staff, increased job satisfaction, and also enhanced the awareness rate of prevention knowledge among patients, thereby improving the management status of thrombophilia in orthopedic inpatients.

Objective:To construct a multidisciplinary collaborative intelligent prevention and treatment system for orthopedic thrombophilia based on advanced intelligent analysis technology and to evaluate its application effectiveness in the management of orthopedic thrombophilia.Methods:Established a clinical multidisciplinary medical team guided by early warning management and human-computer interaction theory, and builded a multidisciplinary collaborative intelligent prevention and treatment system for orthopedic thrombophilia based on intelligent analysis technology.Adopting a prospective pre-and post control study method, 674 orthopedic inpatients at the Second Affiliated Hospital of Nanchang University from February 2021 to October 2022 were selected as study participants by convenient sampling method and divided into a control group (308 cases) and an observation group (366 cases) according to their admission periods. The control group underwent conventional management methods for thrombophilia. In contrast, the observation group utilized a multidisciplinary collaborative intelligent prevention and treatment system for orthopedic thrombophilia for intelligent management methods. The two groups were compared regarding risk assessment rates, assessment accuracy, assessment efficiency, dynamic assessment completion rate, knowledge awareness rates, implementation rates of multidisciplinary collaborative preventive measures, and thrombophilia incidence rates.Results:The multidisciplinary collaborative intelligent prevention and treatment system for orthopedic thrombophilia mainly included four personnel ports (doctor end, nurse end, patient or caregiver end, medical quality control end) and eight modules (patient intelligent scoring, risk grading warning, dynamic evaluation of prevention contraindications, prevention measure decision-making, health education, inpatient data monitoring, department indicator statistics, medical management). Both groups of patients completed the study. There were 238 males and 70 females in the control group, aged (42.83 ± 8.69) years old. There were 278 males and 88 females in the observation group, aged (42.35 ± 8.13) years old. The risk assessment rate, assessment accuracy rate, and dynamic assessment completion rate of the observation group for thrombophilia were 100.00% (366/366), 98.90% (362/366), and 100.00% (366/366), respectively, all higher than the control group's 94.15% (290/308), 90.58% (279/308), and 91.55% (282/308), and the differences were statistically significant ( χ2=21.99, 24.88, 32.16, all P<0.01). The knowledge awareness rate of preventing thrombophilia among high-risk patients in the observation group was 95.90% (211/220), the implementation rates of basic prevention, physical prevention, drug prevention, and combined prevention in the multidisciplinary collaborative prevention measures were 87.37% (173/198), 97.72% (215/220), 39.09% (86/220), 46.37% (102/220), and 27.73% (61/220), respectively, all higher than the control group's 85.86% (170/198), 24.74% (49/198), 30.81% (61/198), and 12.12% (24/198), and the differences were statistically significant ( χ2 values were 9.81-20.19, all P<0.05). The risk assessment time for the observation group was (3.95 ± 1.03) minutes, and the incidence of thrombophilia was 1.91% (7/366), both lower than the control group's (9.56 ± 1.65) minutes and 7.47% (23/308), with statistically significant differences ( t=53.78, χ2=6.33, both P<0.05). Conclusions:The application of the multidisciplinary collaborative intelligent prevention and treatment system for orthopedic thrombophilia has improved the implementation rate of prevention and treatment interventions by medical staff, increased job satisfaction, and also enhanced the awareness rate of prevention knowledge among patients, thereby improving the management status of thrombophilia in orthopedic inpatients.

Objective:To explore the effect of secreted frizzled-related protein 3 (sFRP3) on tau aggregation.Methods:(1) Twelve wild-type C57BL/6J mice and 12 P301S mutant tau transgenic (tau P301S) mice were selected; Western blotting was used to detect the sFRP3 protein expression in the brain tissues; co-immunoprecipitation experiment was conducted to verify endogenous sFRP3 binding to tau; and double immunofluorescent staining was performed to observe whether sFRP3 co-localized with phosphorylated tau. (2) Recombinant human tau (K18) and sFRP3 protein were purified, and pre-formed fibrils (PFFs) containing only K18 or mixed PFFs (containing both sFRP3 and K18) were prepared; His pull-down assay was adopted to verify exogenous purified sFRP3 binding to tau. Aggregation of these two types of PFFs was observed by thioflavin T (ThT) fluorescence,and anti-digestibility of these two types of PFFs was detected by proteinase K (PK) assay. Ultrastructure of two types of PFFs was observed under transmission electron microscope. (3) HEK293 cells stably expressing green fluorescent protein (GFP) and tau repeat domain (GFP-tau RD HEK293) were treated with the two tpyes of PFFs; intracellular tau aggregation was observed by immunofluorescence; intracellular soluble or insoluble component was evaluated by density gradient lysis. SH-SY5Y cells were treated with the two types of PFFs; cell counting kit-8 (CCK-8) assay was used to detect cell viability; Western blotting was used to detect the expressions of apoptosis-related proteins (Bcl-2-associated X protein [Bax] and cleaved caspase-3); double staining with propidium iodide (PI) and Hoechst 33342, and TUNEL were used to detect cell apoptosis. Primary neurons were treated with the two types of PFFs; density of dendritic spines was measured by 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate (DiI) staining; expressions of synaptic proteins, such as synapsin I and vesicle-associated membrane protein 2 (VAMP2), were detected by Western blotting and double immunofluorescent staining. Results:(1) sFRP3 expression in the brain tissues of tau P301S mice was significantly higher than that in wild-type mice (1.10±0.05 vs. 0.79±0.06, P<0.05). In the brain tissues of wild-type mice, endogenous sFRP3 could bind to tau, and in the brain tissues of tau P301S mice, sFRP3 and phosphorylated tau were co-localized. (2) Exogenous tau and sFRP3 could interact with each other. After constant temperature oscillation for approximately 180 minutes, the ThT fluorescent intensity in mixed PFFs was significantly higher than that in K18 PFFs. Remaining proteins of mixed PFFs were significantly increased compared with those of K18 PFFs after the same digestion time of 1 and 2 μg/mL PK (0.77±0.02 vs. 0.67±0.03; 0.52±0.04 vs. 0.33±0.02, P<0.05). The ultrastructure of mixed PFFs was longer and more compact than K18 PFFs. (3) Compared with K18 PFFs, mixed PFFs formed more intracellular tau aggregation points and had more insoluble components (insoluble protein and soluble protein ratio: 0.43±0.04 and 0.92±0.08), with significant differences ( P<0.05). Compared with K18 PFFs, mixed PFFs had significantly decreased SH-SY5Y cell viability (0.44±0.01 vs. 0.24±0.02), significantly up-regulated Bax and cleaved caspase-3 protein expressions (0.71±0.04 vs. 0.87±0.04; 0.60±0.06 vs. 0.88±0.03), significantly increased percentage of apoptotic cells (PI/Hoechst staining: 8.00%±0.49% vs. 18.11%±1.13%; TUNEL staining: 6.62%±0.91% vs. 14.94%±1.32%, P<0.05). Compared with the K18 PFFs group, the mixed PFFs group had significantly decreased density of dendritic spines ([5.7±0.28]/10 μm vs. [2.7±0.29]/10 μm), synapsin I and VAMP2 expressions (0.95±0.02 vs. 0.48±0.04; 0.88±0.03 vs. 0.52±0.06), and average fluorescent intensity of synapsin I and VAMP2 in the primary neurons (7.73±0.70 vs. 2.74±0.34; 6.14±0.60 vs. 2.96±0.54, P<0.05). Conclusion:sFRP3 interacts with tau to promote tau aggregation, and enhance the cytotoxic effect of tau aggregation.

Objective To observe the clinical efficacy of Quxie Capsule combined with fruquintinib in the treatment of metastatic colorectal cancer(mCRC).Methods A prospective,non-randomized,controlled study was used to collect patients with mCRC who planned to receive third-line treatment after second-line treatment at Xiyuan Hospital of China Academy of Chinese Medical Sciences,Guang'anmen Hospital of China Academy of Chinese Medical Sciences,Dongfang Hospital Beijing University of Chinese Medicine,and Xinjiang Uygur Autonomous Region Hospital of Traditional Chinese Medicine.The treatment group received Quxie Capsule combined with fruquintinib.The control group was treated with fruquintinib.The primary outcome measure was third-line overall survival(OS),and the secondary outcome measure was third-line progression-free survival(PFS).Results A total of 142 patients with mCRC were included in this study(79 in the treatment group and 63 in the control group).The median OS(mOS)was 19.0 months in the treatment group and 8.1 months in the control group,and the difference was statistically significant[HR=0.285,95%CI(0.183,0.436),P<0.001].The median PFS(mPFS)in the treatment group was 7 months,mPFS in the control group was 2 months,and the difference was statistically significant[HR=0.248,95%CI(0.165,0.362),P<0.001].In subgroups,such as age,gender,primary site,peritoneal metastasis,and genotype,mOS in the treatment group was longer than in the control group(P<0.001).Multivariate COX proportional hazard model analysis showed that peritoneal metastasis was an independent prognostic factor and the risk of death increased 2.14 times.The combination with Quxie Capsule was a protective factor,reducing the risk of death by 76.8%.Conclusion The Quxie Capsule combined with fruquintinib can prolong mOS survival and mPFS of mCRC treated in the third-line stage.

Objective:To establish the myocardial ischemia-reperfusion injury (MIRI) model by ligation of the left ventricular branch of coronary artery in rabbits.Methods:Totally 36 New Zealand white rabbits were randomly divided into 3 groups according to the random number table method, including the sham group ( n=6), the model group ( n=15), and the sustained ischemia group ( n=15). The rabbits were placed under general anesthesia, then endotracheal intubation and common carotid artery intubation were performed. The intercostal muscle between the 3rd and 4th ribs of the left thorax was divided with the aid of a ventilator. The left ventricular branch was located and processed according to the different groups. After successful modeling, the gross morphological change of the heart was observed by naked eye, and the survival rate and modeling success rate of rabbits in each group were calculated respectively. Record the waveform of limb lead Ⅱ electrocardiogram before left ventricular branch ligation (N), 45 minutes of ischemia (I45), 15 minutes of reperfusion (R15), 30 minutes of reperfusion (R30), and 60 minutes of reperfusion (R60). Serum cardiac troponin Ⅰ (cTnⅠ) level was detected by enzyme-linked immunosorbent assay (ELISA), myocardial infarct size ratio was detected by 2, 3, 5-triphenyltetrazolium chloride (TTC) staining, and the change of myocardial tissue changes were detected by hematoxylin-eosin (HE) staining. Results:The survival rate of the rabbits was 93.33% (14/15) in the model group, and the success rate of MIRI modeling was 86.67% (13/15). In the model group, the ST segment (5.00±0.71) mm at I45 was higher than that before the ligation (1.20±0.27) mm, the difference was statistically significant ( P<0.01), and it was stable throughout the whole ischemia period. After ligation removal, the ST segment decreased to (3.00±0.61) mm at R15, (2.20±0.45) mm at R30, and (1.30±0.27) mm at R60. There were statistically significant differences between I45 and N, R15 and I45, and R60 and R15 (all P<0.01). The pathological Q-wave was (1.60±0.55) mm at R15, and decreased to (3.60±0.22 and 5.10±0.22) mm at R30 and R60, respectively. There were statistically significant differences between R30 and R15, R60 and R30, and R60 and R15 (all P<0.01). ST segment (6.10±0.42, 5.80±0.45, 5.60±0.22, and 5.30±0.27) mm at I45, I60, I75 and I105 respectively were higher than the ST segment (1.10±0.22) mm at N in the sustained ischemia group, and the differences were statistically significant (all P<0.01). The serum cTnⅠlevels in the model group at N, I45, R30 and R60 were (62.74±1.60, 97.60±6.36, 159.30±17.64, and 166.40±18.56) ng/L, respectively, and the difference between I45 and N was statistically significant ( P<0.05). There were statistically significant differences between R30 and I45, R60 and I45, and R30 and N (all P<0.01). The serum cTnⅠlevels in the sustained ischemia group were (69.00±4.85, 107.90±7.12, 140.60±10.96, 171.00±15.40) ng/L at N, I45, I75 and I105, respectively. There were statistically significant differences between I45 and N, I75 and I45, and I105 and I75 (all P<0.01). The infarct size ratios of the model group and the sustained ischemia group were 39.93% and (52.16±0.06) %, respectively, and the difference was statistically significant ( P<0.05). Conclusions:The method of establishing a MIRI model by ligating the left ventricular branch of the coronary artery in rabbits is simple to operate, with stable and reliable, and the success rate of modeling is high.

Objective:To investigate the application value of the maximum standardized uptake value (SUVmax) of 18F prostate-specific membrane antigen (PSMA) PET/CT combined with the minimum apparent diffusion coefficient (ADCmin) of biparametric magnetic resonance imaging (bpMRI) in predicting pathological upgrading after radical prostatectomy (RP) for prostate cancer. Methods:The data of 89 patients with localized prostate cancer treated at Beijing Hospital from April 2019 to October 2023 were retrospectively analysed. The average age of patients was (68.4±7.0) years old, with prostate-specific antigen (PSA) level of 7.7 (5.4, 12.9) ng/ml, prostate volume of 34.6 (26.9, 47.1) ml, tumor diameter of 1.3 (1.0, 1.8) cm, prostate imaging reporting and data system(PI-RADS) score of 5 in 29 cases (32.6%), clinical stage ≥T 3 in 13 cases (14.6%). There were 31 cases (34.8%) in group 1 of targeted biopsy International Society of Urological Pathology (ISUP)grading groups, 36 cases (40.4%) in group 2, 11 cases (12.4%) in group 3, and 11 cases (12.4%) in group 4. All patients underwent 18F-PSMA PET/CT and bpMRI examinations before RP. The index lesion, identified as the highest Gleason score in pathological whole-mount sections, were outlined. SUVmax and ADCmin values were calculated from the images' region of interest. Pathological upgrading was defined as the post-RP grade group higher than the targeted-biopsy grade group. Clinical data of patients with and without pathological upgrading were compared. Spearman correlation coefficient analysis was used to assess the correlation between SUVmax and ADCmin. Multivariate logistic regression analysis was conducted to evaluate the factors influencing pathological upgrading. Receiver operating characteristic (ROC) curve analysis was employed to assess the predictive value of each indicator for pathological upgrading. Results:Among the 89 cases, 31 cases (34.8%) experienced pathological upgrading. Compared with the patients without pathological upgrading, the SUVmax [11.3 (8.1, 16.4) vs. 6.7 (4.6, 9.2)], SUVmax/ADCmin ratio [3.1 (2.0, 4.6) vs. 1.4 (0.9, 2.1)], PSA [9.8 (6.3, 15.6) ng/ml vs. 7.1 (5.1, 10.5) ng/ml], PSA density [0.3 (0.2, 0.5) ng/ml 2 vs. 0.2 (0.1, 0.3) ng/ml 2], and post-RP ISUP grade group [≥3 group 17 cases (54.8%) vs. 13 cases(22.4%) ]were higher in patients with pathological upgrading, while ADCmin [3.8 (3.0, 5.3) ×10 -4 mm 2/s vs. 5.2 (3.6, 6.1)×10 -4 mm 2/s] and targeted biopsy ISUP grade group [≤2 group 27 cases(87.1%) vs. 40 cases(69.0%) ] were lower (all P<0.05). Spearman analysis showed a negative correlation between SUVmax and ADCmin ( R = -0.227, P = 0.032). Multivariate logistic regression analysis revealed that SUVmax ( OR = 1.108, 95% CI 1.020-1.238), ADCmin ( OR=0.607, 95% CI 0.390-0.874), and SUVmax/ADCmin ratio ( OR = 1.815, 95% CI 1.282-2.949) independently predicted pathological upgrading. The AUC of the SUVmax/ADCmin ratio for predicting pathological upgrading (AUC = 0.817) was higher than that of SUVmax (AUC = 0.774) and ADCmin (AUC=0.686), indicating a higher predictive efficiency. Conclusions:SUVmax, ADCmin, and SUVmax/ADCmin ratio can independently predict pathological upgrading in targeted biopsy of prostate cancer. The SUVmax/ADCmin ratio has a stronger predictive value for pathological upgrading.

Objective To observe the clinical efficacy of Quxie Capsule combined with fruquintinib in the treatment of metastatic colorectal cancer(mCRC).Methods A prospective,non-randomized,controlled study was used to collect patients with mCRC who planned to receive third-line treatment after second-line treatment at Xiyuan Hospital of China Academy of Chinese Medical Sciences,Guang'anmen Hospital of China Academy of Chinese Medical Sciences,Dongfang Hospital Beijing University of Chinese Medicine,and Xinjiang Uygur Autonomous Region Hospital of Traditional Chinese Medicine.The treatment group received Quxie Capsule combined with fruquintinib.The control group was treated with fruquintinib.The primary outcome measure was third-line overall survival(OS),and the secondary outcome measure was third-line progression-free survival(PFS).Results A total of 142 patients with mCRC were included in this study(79 in the treatment group and 63 in the control group).The median OS(mOS)was 19.0 months in the treatment group and 8.1 months in the control group,and the difference was statistically significant[HR=0.285,95%CI(0.183,0.436),P<0.001].The median PFS(mPFS)in the treatment group was 7 months,mPFS in the control group was 2 months,and the difference was statistically significant[HR=0.248,95%CI(0.165,0.362),P<0.001].In subgroups,such as age,gender,primary site,peritoneal metastasis,and genotype,mOS in the treatment group was longer than in the control group(P<0.001).Multivariate COX proportional hazard model analysis showed that peritoneal metastasis was an independent prognostic factor and the risk of death increased 2.14 times.The combination with Quxie Capsule was a protective factor,reducing the risk of death by 76.8%.Conclusion The Quxie Capsule combined with fruquintinib can prolong mOS survival and mPFS of mCRC treated in the third-line stage.

Stem/progenitor cells are important for salivary gland development, homeostasis maintenance, and regeneration following injury. Keratin-14⁺ (K14⁺) cells have been recognized as bona fide salivary gland stem/progenitor cells. However, K14 is also expressed in terminally differentiated myoepithelial cells; therefore, more accurate molecular markers for identifying salivary stem/progenitor cells are required. The intraflagellar transport (IFT) protein IFT140 is a core component of the IFT system that functions in signaling transduction through the primary cilia. It is reportedly expressed in mesenchymal stem cells and plays a role in bone formation. In this study, we demonstrated that IFT140 was intensively expressed in K14⁺ stem/progenitor cells during the developmental period and early regeneration stage following ligation-induced injuries in murine submandibular glands. In addition, we demonstrated that IFT140⁺/ K14⁺ could self-renew and differentiate into granular duct cells at the developmental stage in vivo. The conditional deletion of Ift140 from K14⁺ cells caused abnormal epithelial structure and function during salivary gland development and inhibited regeneration. IFT140 partly coordinated the function of K14⁺ stem/progenitor cells by modulating ciliary membrane trafficking. Our investigation identified a combined marker, IFT140⁺/K14⁺, for salivary gland stem/progenitor cells and elucidated the essential role of IFT140 and cilia in regulating salivary stem/progenitor cell differentiation and gland regeneration.
Animals ; Carrier Proteins/metabolism* ; Cell Differentiation ; Keratin-14/metabolism* ; Mice ; Osteogenesis ; Salivary Glands/metabolism* ; Stem Cells

Objective:To investigate the safety and effectiveness of Willis covered stent in patients having carotid artery rupture during transnasal endoscopic pituitary tumor resection.Methods:A retrospective analysis was performed. Six patients having carotid artery rupture during transnasal endoscopic pituitary tumor resection admitted to the 3 hospitals from May 2016 to December 2019 were chosen; their clinical data were collected. The surgical processes and complications were concluded, and the prognoses were evaluated by modified Rankin scale (mRS).Results:One patient was treated with intraoperative simple tamponade compression for hemostasis, and died for massive intracranial hemorrhage 2 weeks after surgery. Five patients were occluded by Willis covered stents; the occluded success rate was 100% but ophthalmic arteries were blocked in all. During the perioperative period, diabetes insipidus occurred in one patient and incomplete oculomotor paralysis occurred in one patient; 5 patients were followed up for 3-12 months: MRI indicated subtotal resection of tumor in 4 patients and total resection in one patient, no new bleeding or ischemic stroke events occurred in these 5 patients, and the prognosis was good.Conclusion:Willis covered stent is safe and effective in patients having carotid artery rupture during transnasal endoscopic pituitary tumor resection.