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1.
Chinese Pharmacological Bulletin ; (12): 426-430, 2024.
Article Zh | WPRIM | ID: wpr-1013652

Glucagon-like peptide-1 ( GLP-1 ) is secreted by gut enteroendocrine cells. GLP-1 receptor agonists ( GLP-1 RAs) control glucose-related augmentation of insulin and suppress glu-cagon secretion. GLP-lRAs also inhibit gastric emptying, food intake and limit weight gain. In the past decade, significant progresses have been made in the investigation on the effects of GLP-1 RAs on cardiovascular system. The potential advantages of oral small-molecule GLP-1 RAs could improve the application of this class of drugs. This review highlights the multiple cardiovascular profiles of GLP-1 RAs in the treatment of cardiovascular diseases to provide new insights into cardiovascular benefits of GLP-1 RAs.

2.
Article En | MEDLINE | ID: mdl-37957490

PURPOSE: This study was designed to explore the effects of interleukin 33 (IL-33) on the progression of atherosclerosis and the possible mechanism. METHODS: The adhesion assay was performed on isolated peripheral blood mononuclear cells (PBMCs) and human umbilical vein endothelial cells (HUVEC). The expression of proteins and messenger RNA (mRNA) were detected by western blot and quantitative real-time polymerase chain reaction (PCR), including intercellular cell adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and P-selectin. The effect of IL-33 on the interaction of growth stimulation expressed gene 2 (ST2) with myeloid differentiation factor 88 (MyD88) and interleukin-1 receptor-associated kinase (IRAK) 1/4 were investigated using co-immunoprecipitation assay. An apolipoprotein (Apo) E-/- mice model was used to confirm the effect of IL-33 on atherosclerosis progression. Area of plaques was recorded by hematoxylin-eosin (H&E) staining. The severity of atherosclerosis plaque was evaluated using immunohistochemistry assay, and lipid accumulation was measured by an oil red O staining. In contrast, western blot was performed to detect the expression levels of VCAM-1, extracellular signal-regulated kinase (ERK) 1/2, and interferon regulatory factor 1 (IRF1). RESULTS: Our study observed that IL-33 suppressed cell adhesion and the expression of VCAM-1 in tumor necrosis factor-α (TNF-α) exposed HUVEC. Moreover, the addition of IL-33 significantly inhibited the expression of IRF1 and the binding level of IRF1 to VCAM-1 and also promoted the phosphorylation level of IRAK1/4 and ERK1/2 compared to TNF-α-stimulated HUVEC. The ST2 neutralizing antibody or ERK pathway inhibitor SCH772984 reversed the regulatory effects of IL-33 on HUVEC, suggesting that IL-33 suppressed IRF1 and VCAM-1 dependent on binding to ST2 and activating the ERK1/2 signaling pathway. Further investigation in vivo confirmed that IL-33 decreased the expressions of IRF1 and VCAM-1 by activating the phosphorylation of ERK1/2 in the thoracic aorta of Apo E-/- mice. CONCLUSION: In conclusion, our results demonstrated that IL-33 plays a protective role in the progression of atherosclerosis by inhibiting cell adhesion via the ERK1/2-IRF1-VCAM-1 pathway. This study may provide a potential therapeutic way to prevent the development of atherosclerosis.

3.
Hum Gene Ther ; 34(15-16): 719-731, 2023 08.
Article En | MEDLINE | ID: mdl-37427415

The highly conserved ribosomal protein L34 (RPL34) has been reported to play an essential role in the progression of diverse malignancies. RPL34 is aberrantly expressed in multiple cancers, although its significant in colorectal cancer (CRC) is currently unclear. Here, we demonstrated that RPL34 expression was higher in CRC tissues than in normal tissues. Upon RPL34 overexpression, the ability of proliferation, migration, invasion, and metastasis of CRC cells were significantly enhanced in vitro and in vivo. Furthermore, high expression of RPL34 accelerated cell cycle progression, activated the JAK2/STAT3 signaling pathway, and induced the epithelial-to-mesenchymal transition (EMT) program. Conversely, RPL34 silencing inhibited the CRC malignant progression. Utilizing immunoprecipitation assays, we identified the RPL34 interactor, the cullin-associated NEDD8-dissociated protein 1 (CAND1), which is a negative regulator of cullin-RING ligases. CAND1 overexpression reduced the ubiquitin level of RPL34 and stabilized RPL34 protein. CAND1 silencing in CRC cells resulted in a decrease in the ability of proliferation, migration, and invasion. CAND1 overexpression promoted CRC malignant phenotypes and induced EMT, and RPL34 knockdown rescued CAND1-induced CRC progression. In summary, our study indicates that RPL34 acts as a mediator, is stabilized by CAND1, and promotes proliferation and metastasis, in part, through the activation of the JAK2/STAT3 signaling pathway and induction of EMT in CRC.


Colorectal Neoplasms , Cullin Proteins , Humans , Cullin Proteins/genetics , Cullin Proteins/metabolism , Down-Regulation , Cell Movement/genetics , Signal Transduction , Cell Proliferation/genetics , Colorectal Neoplasms/metabolism , Cell Line, Tumor , Epithelial-Mesenchymal Transition/genetics , Gene Expression Regulation, Neoplastic , Neoplasm Metastasis , Janus Kinase 2/genetics , Janus Kinase 2/metabolism , STAT3 Transcription Factor/genetics , STAT3 Transcription Factor/metabolism
4.
Front Psychol ; 14: 1130654, 2023.
Article En | MEDLINE | ID: mdl-37063524

Objective: This study explored the relationship between college students' physical activity motivation and exercise behavior and constructed a chain mediation model through the mediating roles of exercise climate and exercise self-efficacy. Methods: By random sampling, 1,032 college students were investigated using the Exercise Motivation Scale, Physical Exercise Rating Scale, Exercise Climate Scale, and Exercise Self-Efficacy Scale. Results: (1) There was a huge positive correlation between exercise motivation and exercise behavior (r = 0.240, p < 0.01), and the immediate ways of linking exercise motivation to exercise behavior were critical (ß = 0.068, t = 0.040, p < 0.01). (2) Exercise motivation could positively predict exercise climate (ß = 0.373, t = 0.061, p < 0.01) and exercise self-efficacy (ß = 0.174, t = 0.039, p < 0.01), and exercise climate could emphatically foresee exercise behavior (ß = 0.302, t = 0.051, p < 0.01). Exercise self-efficacy could foresee exercise behavior decidedly (ß = 0.190, t = 0.048, p < 0.01). (3) Exercise climate and exercise self-efficacy play a critical intervening role between exercise motivation and exercise behavior. The intercession impact is explicitly made out of aberrant impacts created in three ways: exercise motivation → exercise climate → exercise behavior (mediating effect value: 0.113); exercise motivation → exercise self-efficacy → exercise behavior (mediating effect value: 0.033); exercise motivation → exercise climate → exercise self-efficacy → exercise behavior (mediating effect value: 0.027). Conclusion: (1) Exercise climate, exercise self-efficacy, and exercise behavior can all be significantly predicted by exercise motivation, suggesting that exercise motivation may help to enhance these variables. (2) In addition to having a direct impact on exercise behavior, exercise motivation can also have an indirect impact through the separate mediating effects of exercise climate and exercise self-efficacy as well as the chain mediating effect of exercise climate and exercise self-efficacy, which is crucial for encouraging college students to engage in physical activity.

5.
Turk J Pediatr ; 65(1): 176-179, 2023.
Article En | MEDLINE | ID: mdl-36867001

BACKGROUND: A magnetic ball is a toy for children that can cause physical injury when used improperly. The injury of urethra and bladder caused by magnetic ball is rarely reported. CASE: Here we present a case of self-inflicted intravesical insertion of 83 magnetic balls by a 10-year-old boy. Preliminary diagnosis was made by a plain radiograph of the pelvis and ultrasonic examination of bladder and all the magnetic balls were removed under cystoscopy successfully. CONCLUSIONS: For children with recurrent bladder irritation, the possibility of bladder foreign body should be considered. Surgery is an effective method. For patients without serious complications, cystoscopy is the gold standard for diagnosis and treatment.


Foreign Bodies , Urinary Bladder , Male , Child , Humans , Urinary Bladder/diagnostic imaging , Urinary Bladder/surgery , Foreign Bodies/diagnostic imaging , Foreign Bodies/surgery , Physical Examination , Magnetic Phenomena
6.
Eur J Immunol ; 53(4): e2048980, 2023 04.
Article En | MEDLINE | ID: mdl-36647268

Epigenetics, as a discipline that aims to explain the differential expression of phenotypes arising from the same gene sequence and the heritability of epigenetic expression, has received much attention in medicine. Epigenetic mechanisms are constantly being discovered, including DNA methylation, histone modifications, noncoding RNAs and m6A. The immune system mainly achieves an immune response through the differentiation and functional expression of immune cells, in which epigenetic modification will have an important impact. Because of immune infiltration in the tumor microenvironment, immunotherapy has become a research hotspot in tumor therapy. Epigenetics plays an important role in autoimmune diseases and cancers through immunology. An increasing number of drugs targeting epigenetic mechanisms, such as DNA methyltransferase inhibitors, histone deacetylase inhibitors, and drug combinations, are being evaluated in clinical trials for the treatment of various cancers (including leukemia and osteosarcoma) and autoimmune diseases (systemic lupus erythematosus, rheumatoid arthritis, systemic sclerosis). This review summarizes the progress of epigenetic regulation for cancers and autoimmune diseases to date, shedding light on potential therapeutic strategies.


Autoimmune Diseases , Neoplasms , Humans , Autoimmunity/genetics , Epigenesis, Genetic , Translational Science, Biomedical , DNA Methylation , Neoplasms/genetics , Neoplasms/therapy , Tumor Microenvironment
7.
Article Zh | WPRIM | ID: wpr-981679

OBJECTIVE@#To investigate the repair method of type Ⅱc injury in the lateral meniscus popliteal tendon area based on the porcine knee joint.@*METHODS@#Eighteen commercially available fresh porcine knee joints were randomly divided into 3 groups ( n=6). After preparing a type Ⅱc injury in the lateral meniscus popliteal tendon area, and the anterior (group A), posterior (group B), or anterior and posterior (group C) of the popliteal hiatus (PH) was sutured by vertical mattress. The tension meter was used to apply gradient tensions of 2, 4, 6, 8, and 10 N along the tibial plateau horizontally, respectively, to pull the midpoint of the lateral meniscus popliteal tendon area. The displacement values before modeling, after modeling, and after suture were recorded. The reduction value of lateral meniscus displacement and reduction rate after suture were calculated and compared between groups.@*RESULTS@#There was no significant difference between groups ( P>0.05) in the displacement values before modeling, after modeling, and after suture under different tensions. There was no significant difference between groups A and C ( P>0.05) in the reduction value of lateral meniscus displacement and reduction rate after suture under different tensions. The reduction value of lateral meniscus displacement and reduction rate after suture in group B were lower than those in groups A and C. The reduction value of lateral meniscus displacement under tension of 2 N and the reduction rates under tensions of 2, 4, and 6 N between groups A and B showed significant differences ( P<0.05). The reduction value of lateral meniscus displacement and the reduction rate under tensions of 2, 4, and 6 N between groups B and C showed significant differences ( P<0.05).@*CONCLUSION@#Suturing the anterior area of PH is the key to repairing type Ⅱc injury of lateral meniscus popliteal tendon area.


Animals , Humans , Knee , Knee Joint , Menisci, Tibial/surgery , Swine , Tendons , Tibia
8.
Article Zh | WPRIM | ID: wpr-979524

@#Objective     To investigate the effect and prognosis of patients with ventricular septal rupture after myocardial infarction treated by surgical repair combining an occluder and a patch. Methods     Clinical data of 42 patients with myocardial infarction complicated with ventricular septal rupture admitted to the First Affiliated Hospital of Zhengzhou University from January 2010 to September 2021 were retrospectively analyzed. According to the surgical methods, 27 patients were divided into a traditional group, including 17 males and 10 females, with an average age of 62.81±6.81 years, who were repaired by patch only, and 15 patients were divided into a modified group, including 11 males and 4 females, with an average age of 64.27±9.24 years, who were repaired by surgery combining an occluder and a patch. Perioperative and follow-up data of the two groups were compared and analyzed. Results     There were statistical differences between the two groups in preoperative Killip grading, rate of intra-aortic balloon pump use, interval from myocardial infarction to operation, and the number of culprit artery (P<0.05). There was no statistical difference in other preoperative data, the cardiopulmonary bypass time, aortic cross-clamping time, postoperative hospital stay or in-hospital death rate between the two groups (P>0.05). No residual shunt occurred in the modified group, and the difference was statistically significant compared with the traditional group (P=0.038). There was no statistical difference in other complications between the two groups (P>0.05). The median follow-up time was 4 years. Two patients in the traditional group and one in the modified group died during follow-up. The follow-up cardiac function grading of patients in the modified group was statistically different from that in the traditional group (P=0.023). Conclusion     The perioperative  mortality of ventricular septal rupture after myocardial infarction is high, but the long-term effect is satisfactory. Surgical repair combining an occluder and a patch is a safe and effective treatment for ventricular septal rupture, which can effectively reduce postoperative residual shunt.

9.
Article Zh | WPRIM | ID: wpr-981462

Coronary artery disease(CAD) caused by atherosclerosis(AS) is a major contributor to the global burden of disease. The pathogenesis of CAD is complex, and the subset and function of cardiac macrophages are important factors affecting the occurrence and development of AS and the prognosis of CAD. Recent studies have shown that some traditional Chinese medicine(TCM) formulas and active ingredients can regulate macrophage subsets involved in the inflammation, injury, and repair process of CAD. This paper summarized the significant role of macrophages in AS and myocardial infarction. Based on the plasticity of macrophages, this paper elaborated that traditional Chinese medicine prevented and attenuated AS by regulating macrophage subsets, reducing the level of inflammatory factors, and promoting macrophage autophagy.Traditional Chinese medicine participated in the cardiac repair process after myocardial infarction by accelerating the recruitment of M2 macrophages, inhibiting the polarization of M1 macrophages mediated by glycolysis, inhibiting M1 macrophage-mediated cardiac nerve remodeling, and promoting M2 macrophage-mediated angiogenesis. In addition, in vitro studies on the regulation of macrophage subsets by the active ingredients of traditional Chinese medicine were also reviewed. It was pointed out that nuclear factor kappa B(NF-κB), adenosine 5'-monophosphate(AMP)-activated protein kinase(AMPK), phosphoinositide 3-kinase/protein kinase B(PI3K/Akt), chemokine(C-C motif) ligand 2/C-C chemokine receptor type 2(CCL2/CCR2) were the key targets and pathways for the regulation of macrophages by TCM.


Humans , Phosphatidylinositol 3-Kinases , Medicine, Chinese Traditional , Myocardial Infarction , Coronary Artery Disease , Inflammation/drug therapy , AMP-Activated Protein Kinases , Macrophages , NF-kappa B
10.
International Eye Science ; (12): 1585-1588, 2023.
Article Zh | WPRIM | ID: wpr-980559

AIM: To investigate the effects of primary acquired nasolacrimal duct obstruction(PANDO)on the tear film and ocular surface using LipiView ocular surface interferometer and Keratograph 5M anterior segment analyzer.METHODS: A self-controlled clinical trials. A total of 40 patients diagnosed with unilateral PANDO for at least 6mo who were admitted to our department from September 2021 to March 2022 were enrolled in the study, and the healthy eyes of the patients were assessed as control group. The LipiView ocular surface interferometer and Keratograph 5M anterior segment analyzer were used to measure the changes in related parameters of the tear film and ocular surface in both eyes.RESULTS: The non-invasive tear meniscus height(NITMH), stimulated NITMH, loss rate of upper meibomian gland, nasal and temporal ciliary redness index, temporal conjunctival redness index of the affected eyes were higher than healthy eyes(P&#x003C;0.05), but there were no statistical differences in the non-invasive break-up time(NIBUT), loss rate of lower meibomian gland, nasal conjunctival redness index, dry eye grading, blink responses, partial blink rate and lipid layer thickness(LLT)between the both eyes(P&#x003E;0.05).CONCLUSION: PANDO may lead to the aggravation of ocular surface inflammation and the loss of upper meibomian gland, and damage the ocular surface of patients. Attention should be paid to the early treatment of PANDO.

11.
Article En | WPRIM | ID: wpr-982290

OBJECTIVE@#To investigate the effect and potential mechanism of dihydromyricetin (Dmy) on H9C2 cell proliferation, apoptosis, and autophagy.@*METHODS@#H9C2 cells were randomly divided into 7 groups, namely control, model, EV (empty pCDH-CMV-MCS-EF1-CopGFP-T2A-Puro vector), IV (circHIPK3 interference), Dmy (50 µ mol/L), Dmy+IV, and Dmy+EV groups. Cell proliferation and apoptosis were detected by cell counting kit-8 assay and flow cytometry, respectivley. Western blot was used to evaluate the levels of light chain 3 II/I (LC3II/I), phospho-phosphoinositide 3-kinase (p-PI3K), protein kinase B (p-AKT), and phospho-mammalian target of rapamycin (p-mTOR). The level of circHIPK3 was determined using reverse transcriptase polymerase chain reaction. Electron microscopy was used to observe autophagosomes in H9C2 cells.@*RESULTS@#Compared to H9C2 cells, the expression of circHIPK in H9C2 hypoxia model cells increased significantly (P<0.05). Compared to the control group, the cell apoptosis and autophagosomes increased, cell proliferation rate decreased significantly, and the expression of LC3 II/I significantly increased (all P<0.05). Compared to the model group, the rate of apoptosis and autophagosomes in IV, Dmy, and Dmy+IV group decreased, the cell proliferation rate increased, and the expression of LC3 II/I decreased significantly (all P<0.05). Compared to the control group, the expressions of p-PI3K, p-AKT, and p-mTOR in the model group significantly reduced (P<0.05), whereas after treatment with Dmy and sh-circHIPK3, the above situation was reversed (P<0.05).@*CONCLUSION@#Dmy plays a protective role in H9C2 cells by inhibiting circHIPK expression and cell apoptosis and autophagy, and the mechanism may be related to PI3K/AKT/mTOR pathway.


Proto-Oncogene Proteins c-akt/metabolism , Signal Transduction , Phosphatidylinositol 3-Kinases/metabolism , TOR Serine-Threonine Kinases/metabolism , Apoptosis , Autophagy
12.
Journal of Geriatric Cardiology ; (12): 341-349, 2023.
Article En | WPRIM | ID: wpr-982196

BACKGROUND@#Familial hypercholesterolemia (FH) is a common autosomal dominant hereditary disease. Its early diagnosis and intervention significantly improve the patient's quality of life. However, there are few types of research on the FH pathogenic genes in China.@*METHODS@#In this study, we recruited a family diagnosed with FH and used whole exome sequencing (WES) to analyze the proband variants. Intracellular cholesterol level, reactive oxygen species (ROS) level, and the expression of pyroptosis-related genes were detected after overexpression of wild-type or variant LDLR in L02 cells.@*RESULTS@#A heterozygous missense variant predicted to be deleterious to LDLR (c.1879G > A, p.Ala627Thr) was identified in the proband. Mechanistically, intracellular cholesterol level, ROS level, and the expression of pyroptosis-related genes, nucleotide-binding oligomerization domain-like receptor family protein 3 (NLRP3) inflammasome and components (caspase 1, apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) and NLRP3), gasdermin D (GSDMD), interleukin (IL) -18, IL-1β was elevated in the variant LDLR group, which was attenuated by inhibition of ROS.@*CONCLUSIONS@#FH is associated with a variant (c.1879G>A, p.Ala627Thr) in the LDLR gene. Regarding the mechanism, the ROS/NLRP3-mediated pyroptosis in hepatic cells may contribute to the pathogenesis of the LDLR variant.

13.
Article Zh | WPRIM | ID: wpr-981744

OBJECTIVE@#To explore the clinical effect of Kirschner wire intramedullary fixation in the treatment of both-bone forearm fractures in children of high altitude area.@*METHODS@#From August 2020 to December 2021, 19 children were treated with Kirschner wire intramedullary fixation including 11 males and 8 females, aged from 4 to 13 years old with an average of (8.16±2.71) years old. The course of disease was 1 to 10 days, with a mean of (4.11±2.51) d. First, close reduction was performed. If the reduction was unsuccessful, limited open reduction was performed, followed by Kirschner wire intramedullary fixation of the radius and ulna. The fracture healing was evaluated by X-ray after operation, and the curative effect was evaluated by Anderson forearm function score standard.@*RESULTS@#The wound healed well after operation, 2 cases had clinical manifestations of needle tail irritation after operation, and the symptoms disappeared after removing the internal fixation. The average follow-up time was(7.68±3.50) months (3 to 14 months). X-ray showed that all fracture healing in follow-up, Anderson forearm function score showed excellent in 16 cases, good in 2 cases and fair in 1 case at the final follow-up.@*CONCLUSION@#Children with fractures in plateau areas often have delayed medical treatment, lack of medical conditions and insufficient compliance. Based on these characteristics, Kirschner wire intramedullary fixation for the treatment of children's double forearm fractures has the advantages of small injury and rapid recovery. It is a kind of operation method that can be popularized.


Male , Female , Humans , Child , Child, Preschool , Adolescent , Bone Wires , Forearm , Altitude , Treatment Outcome , Fractures, Bone/surgery , Fracture Fixation, Internal/methods , Radius Fractures/surgery , Fracture Fixation, Intramedullary/methods
14.
Chinese Journal of Stomatology ; (12): 238-243, 2023.
Article Zh | WPRIM | ID: wpr-970781

Objective: To investigate the normal process of tooth development of C57BL/6 mouse strain by using micro-CT for better understanding about the tooth development of the human being and other species. Methods: A total of 54 C57BL/6 mice were used at postnatal day 1 (P1), P3, P7, P10, P14, P21, P28, P42 and P56 (n=6 for each age group). After euthanasia, the skulls and alveolar bones (with molars) were isolated and scanned by micro-CT scanner. After three dimensional reconstruction, the developmental status of the crown and root(s) for each tooth type was examined in different views. Results: The tooth development of mice from birth to mature (P56) could be divided into three stages. The first stage was from P1 to P14, in which the crowns of all the first, second and third molars had formed, while the roots had not fully developed yet. The second stage was from ablactation (P21) to P28, in which all the roots of the molars had reached their normal length, and the apical foramens had closed. Due to the mastication and occlusal abrasion, the incisors exhibited sharp cutting edges at the buccal enamel layer, and the corresponding molars formed a pit-to-fossa articulated relationship. The third stage was from P42 to P56, in which the root canal differentiation occurred, and 1-2 canal configuration was formed in several flat roots. The development of molar roots had completed and the apexes were enlarged due to the deposition of cementum around. Conclusions: In the process of mouse tooth development, the mineralization of the cusps, followed by crown formation and roots elongation, was precisely regulated in a spatial-temporal pattern. The incisors and the molars exhibited different modes of development.

15.
Chinese Journal of Surgery ; (12): 381-388, 2023.
Article Zh | WPRIM | ID: wpr-970219

Objective: To investigate surgical strategies and the corresponding benefits for patients with perihilar cholangiocarcinoma(pCCA). Methods: A total of 81 patients with pCCA who underwent radical excision in the Department of Biliary and Pancreatic Surgery of Sun Yat-Sen Memorial Hospital between January 2014 and December 2021 were retrospectively collected.The cohort consisted of 50 male and 31 female patients,with an age of (62.5±11.5)years(range:26 to 83 years).Seventy-five cases were diagnosed with jaundice,60 of whom received preoperative biliary drainage,while 20 patients received portal vein embolization.Their serum bilirubin level within one week before the operation(M(IQR)) was 44.3 (41.9) μmol/L(range:8.0 to 344.2 μmol/L).Preoperative imaging examinations were performed to evaluate the Bismuth-Corlette type of pCCA,showing 3,6,21,27,and 24 cases of Bismuth-Corlette type Ⅰ,Ⅱ,Ⅲa,Ⅲb,and Ⅳ,respectively.The primary outcome was overall survival (OS),and the secondary outcomes were relapse-free survival (RFS),90-day postoperative morbidity and 90-day postoperative mortality.OS and RFS were estimated using the Kaplan-Meier method and compared by the Log-rank test.Significant prognostic factors were determined using univariate and multivariable Cox proportional hazard regression analyses. Results: In the cohort of 81 pCCA patients,67 cases(82.7%) underwent major hepatectomy while 3 cases received major hepatectomy combined with pancreaticoduodenectomy.Thirty-four patients underwent hepatectomy combined with vascular resection and reconstruction(18 cases of portal vein resection and reconstruction alone;9 cases of hepatic artery resection and reconstruction alone;7 cases of combination of portal vein and hepatic artery resection and reconstruction).Margin negative(R0 excision) were achieved in 53.1%(43/81) of these patients.The operation duration was (627±136)minutes(range:565 to 940 minutes),and the intraoperative blood loss was 400(455)ml(range:200 to 2 800 ml).The 90-day postoperative mortality was 3.7%(3/81).Grade 3-4 postoperative morbidity was 23.4% (19/81) according to the Clavien-Dindo classification of surgical complications.Up to the last follow-up at September 2022,the follow-up time was 34.0(24.2)months (range:0.4 to 103.6 months).Three patients who died within 90 days after surgery were excluded from the survival analysis.The median OS was 36.10 months (95%CI:18.23 to 42.97 months) and the 1-,3-and 5-year OS rates were 85.3%,46.8% and 27.3%,respectively.The median OS of 41 patients with negative margins was 47.83 months(95%CI:36.90 to 58.80 months) and that of 37 patients with positive margins was 20.47 months(95%CI:10.52 to 30.58 months).The median RFS of 70 patients with R0 and R1 resection was 24.50 months(95%CI:12.15 to 31.85 months)and the 1-,3-and 5-year RFS rates were 65.2%,45.7% and 29.9%,respectively.The median RFS of 41 patients with R0 resection was 38.57 months(95%CI:21.50 to 55.63 months) and that of 29 patients with R1 resection was 10.83 months(95%CI:2.82 to 19.86 months). Conclusions: The primary therapy for pCCA is radical surgical resection.A precise preoperative evaluation and sufficient preparation can reduce postoperative morbidity.Surgical treatment can achieve a better survival outcome by increasing the radical resection rate.

16.
Acta Pharmaceutica Sinica ; (12): 2300-2310, 2023.
Article Zh | WPRIM | ID: wpr-999147

Brain delivery of drugs remains challenging due to the presence of the blood-brain barrier (BBB). With advances in nanotechnology and biotechnology, new possibilities for brain-targeted drug delivery have emerged. Biomimetic nano drug delivery systems with high brain-targeting and BBB-penetrating capabilities, along with good biocompatibility and safety, can enable 'invisible' drug delivery. In this review, five different types of biomimetic strategies are presented and their research progress in central nervous system disorders is reviewed. Finally, the challenges and future prospects for biomimetic nano drug delivery systems in intracerebral drug delivery are summarized.

17.
Acta Pharmaceutica Sinica ; (12): 2715-2726, 2023.
Article Zh | WPRIM | ID: wpr-999026

As a natural product with a long history of medicinal use, parthenolide has aroused great interest of chemists and biologists. Existing studies have shown that it has anti-inflammatory, antitumor and other pharmacological activities, and also revealed its action on NF-κB signaling pathway, DNMT1 enzyme and Wnt/β-catenin signaling pathway. But its biological targets remain to be elucidated systematically. Proteolysis Targeting Chimeras (PROTAC) provides a new strategy for target discovery of natural products, which can be used to explore the panorama of protein changes in cells through proteomic investigation, so as to analyze their potential targets. Based on this idea, current study designed and synthesized 20 parthenolide-derived degraders. After measured their antitumor activity in vitro, selected compounds were carried out the proteomic experiment. Finally, 139 down-regulated differentially expressed proteins were identified and the discovery of parthenolide interacting protein was preliminarily explored.

18.
Article Zh | WPRIM | ID: wpr-998258

ObjectiveTo explore the effect of core stability training on dynamic balance and surface electromyography (sEMG) after anterior cruciate ligament reconstruction (ACLR), and to analyze the correlation between balance index and sEMG. MethodsFrom March to December, 2022, 32 patients with ACLR in Yantai Affiliated Hospital of Binzhou Medical University were randomly divided into control group (n = 16) and experimental group (n = 16). The control group accepted routine rehabilitation treatment, and the experimental group added core stability training, for six weeks. They were evaluated with American Hospital for Special Surgery Knee Score (HSS) and International Knee Documentation Committee Knee Score (IKDC), and the dynamic balance function and sEMG were measured before and after treatment, and the correlation between dynamic balance index and root mean square (RMS) of sEMG was analyzed. ResultsAfter treatment, the scores of HSS and IKDC increased significantly in both groups (|Z| > 3.526, |t| > 63.544, P < 0.001), and were better in the experimental group than in the control group (Z = -2.392, t = 2.650, P < 0.05); the length of gait line and single support line increased significantly, the medial-lateral displacement displacement decreased (|t| > 2.368, Z = -3.516, P < 0.05), and they were better in the experimental group than in the control group (|t| > 2.497, Z = -3.091, P < 0.05); the RMS of gluteus maximus and gluteus medius increased in the experimental group (t = -5.900, Z = -2.741, P < 0.01), and were better than those in the control group (t = 3.930, Z = -3.260, P < 0.01). After treatment, the RMS of gluteus maximus and gluteus medius in both groups were positively correlated with gait line length and single support line length, and were negatively correlated with medial-lateral displacement (|r| > 0.502, P < 0.01). ConclusionCore stability training could significantly improve knee joint function and dynamic balance, and enhance the activation of gluteus maximus and gluteus medius. Dynamic balance is highly correlated with sEMG.

19.
Sichuan Mental Health ; (6): 326-333, 2023.
Article Zh | WPRIM | ID: wpr-987342

BackgroundInternet-based cognitive behavioral therapy (ICBT) is progressively emerging as an efficacious alternative to alleviate anxiety and depression in cancer patients. To date, no Meta-analysis has been conducted specific to the effect of ICBT on anxiety, depression, distress and quality of life in cancer patients. ObjectiveTo assess the effect of ICBT on distress, depression, anxiety and quality of life in cancer patients through a systematic review of the literature. MethodsOn March 28, 2022, PubMed, PsycINFO, Embase, Cochrane Library, Web of Science, CNKI, VIP, Wanfang Data and CBM were retrieved for the randomized controlled trials (RCTs) involving ICBT targeting either distress, depression, anxiety, quality of life or all in cancer patients. After the risk of bias assessment, Stata 17.0 software was used for Meta-analysis. ResultsA total of 12 RCTs with a total sample size of 1 686 patients were included. Meta-analysis revealed that the superiority of ICBT over controls was evident for interventions targeting distress in cancer patients (SMD=-0.547, 95% CI: -1.090~-0.145, P<0.01), while appeared to be less evident for the interventions targeting depression (SMD=-0.652, 95% CI: -1.734~0.002, P=0.051), anxiety (SMD=-1.045, 95% CI: -3.656~0.101, P=0.088) and quality of life (SMD=0.234, 95% CI: -0.064~0.449, P=0.112) in cancer patients,and dropout rate was higher in ICBT group than that in control group (OR=1.795, 95% CI:1.358~2.374, P<0.01). ConclusionICBT is reported to be effective in alleviating distress in cancer patients, whereas results inconsiderable improvements over depression, anxiety and quality of life in cancer patients.

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Article En | WPRIM | ID: wpr-1010343

OBJECTIVES@#At present, there are many reports about the treatment of cricopharyngeal achalasia by injecting botulinum toxin type A (BTX-A) into cricopharyngeal muscle guided by ultrasound, electromyography or CT in China, but there is no report about injecting BTX-A into cricopharyngeal muscle guided by endoscope. This study aims to evaluate the efficacy of endoscopic BTX-A injection combined with balloon dilatation in the treatment of cricopharyngeal achalasia after brainstem stroke, and to provide a better method for the treatment of dysphagia after brainstem stroke.@*METHODS@#From June to December 2022, 30 patients with cricopharyngeal achalasia due to brainstem stroke were selected from the Department of Rehabilitation Medicine, the First Hospital of Changsha. They were randomly assigned into a control group and a combined group, 15 patients in each group. Patients in both groups were treated with routine rehabilitation therapy, while patients in the control group were treated with balloon dilatation, and patients in the combined group were treated with balloon dilatation and BTX-A injection. Before treatment and after 2 weeks of treatment, the patients were examined by video fluoroscopic swallowing study, Penetration-aspiration Scale (PAS), Dysphagia Outcome Severity Scale (DOSS), and Functional Oral Intake Scale (FOIS) were used to assess the swallowing function.@*RESULTS@#In the combined group, 1 patient withdrew from the treatment because of personal reasons. Two weeks after treatment, the scores of DOSS, PAS, and FOIS in both groups were better than those before treatment (all P<0.01), and the combined group was better than the control group (all P<0.001). The effective rate was 85.7% in the combined group and 66.7% in the control group, with no significant difference between the 2 groups (P>0.05).@*CONCLUSIONS@#BTX-A injection combined with balloon dilatation is more effective than balloon dilatation alone in improving swallowing function and is worthy of clinical application.


Humans , Deglutition Disorders/therapy , Esophageal Achalasia/drug therapy , Dilatation/adverse effects , Botulinum Toxins, Type A/therapeutic use , Brain Stem Infarctions/drug therapy , Treatment Outcome
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