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2.
Acta Pharmaceutica Sinica ; (12): 21-26, 2023.
Article in Chinese | WPRIM | ID: wpr-964299

ABSTRACT

Ginsenoside Rg1 is one of the most important saponins in ginseng. It has a wide range of pharmacological activities. It is considered to be a powerful neuroprotective agent. It has neuroprotective effects such as anti-neuroinflammation, anti-oxidative stress, anti-neuronal apoptosis, and enhancing memory. Rg1 shows a good application prospect in the prevention and treatment of neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, stroke, and mental diseases such as depression. This paper reviews the research on the neuroprotective mechanism of Rg1 at home and abroad in recent years, in order to provide new research ideas for the clinical treatment of nervous system diseases.

3.
Article in Chinese | WPRIM | ID: wpr-971419

ABSTRACT

Objective: To introduce a classification of alar retraction, and to discuss the therapeutic strategy of alar retraction with cartilage graft and the satisfaction evaluation of patients after operation. Methods: A retrospective analysis was performed on 88 patients with alar retraction admitted to the Department of Plastic and Aesthetic (Burn) Surgery, the Second Xiangya Hospital of Central South University from January 2015 to December 2020, including 20 males and 68 females, aged 20 to 48 years, with an average age of 28.98 years. All patients underwent external rhinoplasty according to a series of treatment plans determined by the classification of alar retraction based on nostril exposure. Visual Analogue Scale (VAS) and Rhinoplasty Outcomes Evaluation (ROE) were used to conduct satisfaction survey before and 12 months after operation. Wilcoxon signed-rank test was used to analyze patient satisfaction. Results: A total of 88 patients were included in this study. According to the classification of alar retraction based on nostril exposure, 45 cases were mild, 23 cases were moderate, and 20 cases were severe. There were 16 cases of unilateral and 72 cases of bilateral alar retraction. The patients were followed up for 12 to 18 months, with an average of 13.37 months. The VAS score and ROE score after each type of surgery were higher than those before surgery, with statistically significant (all P<0.05). Among them, the difference in VAS score (6.75±1.29) and in ROE satisfaction (67.70±7.38) of patients with severe alar retraction were the most significant improvement. Conclusion: The classification of alar retraction based on nostril exposure in the frontal view can comprehensively evaluate the severity of alar retraction, and makes the treatment algorithms systematic and comprehensive. The satisfaction of patients is relatively high.


Subject(s)
Male , Female , Humans , Adult , Rhinoplasty , Retrospective Studies , Patient Satisfaction , Treatment Outcome , Esthetics , Nose/surgery
4.
Chinese Journal of Microsurgery ; (6): 260-266, 2023.
Article in Chinese | WPRIM | ID: wpr-995500

ABSTRACT

Objective:Exploring the clinical efficacy of using ultra-thin lobulated anterolateral thigh perforator flap(ALTPF) with retrograde separation of perforating vessels from the superficial and deep junction layer of the superficial fascia to repair large soft tissue defects in the foot.Methods:From August 2021 to November 2022, 8 patients (5 males and 3 females) were admitted to the Second Department of Hand and Foot Surgery, the Affiliated Central Hospital of Dalian University of Technology. The patients were 28 to 52 years old in age. The soft tissue defects were located in dorsal and plantar foot. At the plantar foot, the wound involved the weight-bearing area with explosion of bone, tendon or internal fixtures. The area of soft tissue defects was 6.0 cm × 5.0 cm - 16.0 cm × 8.0 cm, and the sizes of ALTPF were 8.0 cm ×5.5 cm - 18.0 cm × 8.5 cm. Preoperative high frequency CUD combined with CTA angiography were employed to locate the 2 flap perforator vessels. By keeping the perforator vessels at center and according to the soft tissue defect area and the wound shape, an ALTPF with a proper size and shape was designed in anterolateral thigh. The perforator were separated in the boundary layer between superficial and deep fascia, where it helped to obviously thin the flap. After the flap was harvested, it was further lobulated between the 2 perforators into 2 lobes after having confirmed the effective blood supply. Finally the lobulated ALTPF was transferred to covered the defect in foot. Cautions should be taken to ensure that the flap covered the weight-bearing area of foot. All the donor sites were directly sutured. Postoperative follow-up was conducted to observe the survival of flaps and the functional recovery of the reconstructed site, also to evaluate the clinical effect. Postoperative follow-up included outpatient visits and reviews over WeChat or telephone. Recovery of the ankle motor function was evaluated according to the American Orthopedic Foot and Ankle Societ (AOFAS) ankle-hind foot score scale.Results:All 8 ALTPF survived. Over 6 to 18 months (10.8 months in average) of follow-up, the transferred flaps had good blood supply, soft in texture, with good elasticity and thin in appearance. Appearance and function of donor sites recovered well, except 1 patient who had mild scar hyperplasia. The plantar flap had good abrasion resistance. No flap damage, bleeding or granulation tissue hyperplasia occurred when walking. The mean score of AOFAS ankle-hind foot score achieved 95.6.Conclusion:The application of ultra-thin lobulated ALTPF with retrograde separation of perforating vessels from the superficial fascia at the junction layer for repairing large soft tissue defects in the foot has good clinical efficacy.

5.
Chinese Journal of Orthopaedics ; (12): 1050-1056, 2023.
Article in Chinese | WPRIM | ID: wpr-993538

ABSTRACT

Artificial intelligence (AI) has a broad application prospect in the field of bone tumor. By utilizing deep learning models and AI technology, it can provide effective assistance in pathological diagnosis of bone tumors, molecular biology diagnosis, imaging diagnosis and clinical data processing, providing patients with more accurate and personalized medical services. In terms of pathological diagnosis, AI can assist doctors to accurately identify and classify tumor types by automatically analyzing and reading a large number of pathological tissue section images. In terms of molecular biology diagnosis, AI discovers key genes and signaling pathways associated with bone tumors by analyzing large-scale genomics and transcriptomics data, which provides the basis for prognostic assessment and individualized treatment development. In terms of imaging diagnosis, AI can assist doctors to quickly and accurately analyze the image characteristics of bone tumors, automatically mark the location, size and morphology of tumors, guide treatment and predict prognosis. AI can also process large-scale clinical data to identify potential clinical features and patterns to assist in risk assessment, treatment decisions, and predicting prognosis. This paper reviews recent studies on the application of AI in the field of bone tumor diagnosis and treatment, with a view to improving the accuracy of bone tumor diagnosis, improving clinical prognosis, and providing a theoretical basis for the integrated development and innovation in the cross-field of medicine and industry.

6.
Chinese Journal of Rheumatology ; (12): 297-303,C5-1, 2023.
Article in Chinese | WPRIM | ID: wpr-992932

ABSTRACT

Objective:To evaluate the value of shear wave elastography (SWE) in skin assessment of Systemic sclerosis (SSc).Methods:A total of 58 SSc patients admitted to Peking University Third Hospital from May 2021 to October 2022 and 41 healthy volunteers were included in the study. Skin shear wave elastography (SWE) was performed at 17 sites defined in modified Rodnan skin score (mRSS) measurement, and shear wave velocity values were recorded to evaluate skin hardness. SPSS 22.0 software was used to analyze the skin hardness of SSc patients and healthy controls, and the correlation between skin hardness of SSc patients and clinical data was analyzed. A logistic regression model was constructed to evaluate the diagnostic efficacy of skin hardness at different sites of SSc patients, and to further select the most practical measurement site.Results:The SWE value of SSc patients was significantly higher than that of healthy control group ( P<0.05). There was a positive correlation between SWE and mRSS in the measurement of bilateral fingers, bilateral dorsal hands, bilateral forearms, fore-chest, abdomen, bilateral thighs, and bilateral dorsal feet. Skin stiffness measured by SWE was significantly correlated with SSc disease activity score (EScSG-DAI), ( r=0.71, P<0.001), disease injury score (SCTC-DI), (P=0.55, P=0.005) and functional score (HAQ-DI), ( r=0.46, P=0.003). Reducing the number of measurement sites to 12 (bilateral fingers, bilateral hands, bilateral forearms, bilateral upper arms, forehead, fore-chest, bilateral dorsum of feet) performs as well as all 17 measurement sites simultaneously in assessing disease activity. Conclusion:SWE is a good evaluation tool to reflect the skin lesions of SSc, which is of great value for the diagnosis and evaluation of the disease. We can further standardize the measurement sites and select the most appropriate evaluation strategy, so as to achieve better clinical application.

7.
Article in Chinese | WPRIM | ID: wpr-990306

ABSTRACT

Objective:To evaluate the clinical application of water-filling with "four-eyes" sign under the guidance of ultrasound in nasal-jejunum intubation for critical patients.Methods:This study was a randomized controlled trial. Eighty patients who needed indwelling nasobenteric tube were selected from June 2021 to April 2022 in the Department of Critical Care Medicine, Xiangya Hospital, Central South University. They were divided into control group ( n=40) and experimental group ( n=40) by systemic randomization. For the patients in the experimental group, the intubation was performed by water-filling with "four-eyes" sign under the guidance of ultrasound. For the control group, the traditional method was applicated under the guidance of ultrasound. Using abdominal X-ray as the gold standard of successful pylorus posterior catheterization, the result of catheterization, time of operation, efficiency of positioning in the two groups were analyzed and compared. Results:In the experimental group, 38 cases were successfully intubated, 2 were failed; in the control group, 27 cases were successfully intubated, 13 were failed, and all the failed cases in the control group were then successfully intubated again by using method of the experimental group. The success rate of tube placement in the experimental group was 95.0% (38/40), which was higher than 67.5% (27/40) in the control group ( χ2 = 9.93, P<0.05). The average time of operation in the experimental group was (45.2 ± 14.2) min, which was significantly lower than (70.2 ± 17.7) min in the control group, the difference was significantly different ( t=-5.51, P<0.05). The specificity, sensitivity, positive predictive value, negative predictive value and diagnostic rate of nasal-jejunum intubation positioning in the experimental group were 100.0% respectively, higher than 38.4%, 77.7%, 72.4%, 45.4%, 65.0% in the control group; the false positive rate, false negative rate in the experimental group were both 0, lower than 22.2%, 61.5% in the control group, with statistically significant differences( χ2 values were 4.69- 16.97, all P<0.05). Conclusions:Water-filling with "four-eyes" sign under the guidance of ultrasound in nasal-jejunum intubation was a new method which can shorten the operation time and increase the success rate for intubation. It has relatively high positioning accuracy and possess valuable clinical application.

8.
Article in Chinese | WPRIM | ID: wpr-987004

ABSTRACT

OBJECTIVE@#To investigate the effect of acetylcorynoline (Ace) for promoting functional recovery of injured spinal cord in rats and explore the underlying mechanism.@*METHODS@#Rat models of spinal cord injury (SCI) were treated with intraperitoneal injection of different concentrations of Ace, with the sham-operated rats as the control group. After the treatment, the changes in motor function of the rats and the area of spinal cord injury were assessed with BBB score and HE staining, and the changes in pro-inflammatory cytokine levels and microglial activation were determined using PCR, ELISA and immunofluorescence staining. In a lipopolysaccharide (LPS)-treated BV2 cell model, the effects of different concentrations of Ace or DMSO on microglial activation and inflammatory cytokine production were observed. Network pharmacology analysis was performed to predict the target protein and signaling mechanism that mediated the inhibitory effect of Ace on microglia activation, and AutoDock software was used for molecular docking between Ace and the target protein. A signaling pathway blocker (Osimertinib) was used to verify the signaling mechanism in rat models of SCI and LPS-treated BV2 cell model.@*RESULTS@#In rat models of SCI, Ace treatment significantly increased the BBB score, reduced the area of spinal cord injury, and lowered the number of activated microglia cells and the levels of pro-inflammatory cytokines (P < 0.05). The cell experiments showed that Ace treatment significantly lower the level of cell activation and the production of inflammatory cytokines in LPS-treated BV2 cells (P < 0.05). Network pharmacology analysis suggested that EGFR was the main target of Ace, and they bound to each other via hydrogen bonds as shown by molecular docking. Western blotting confirmed that Ace inhibited the activation of the EGFR/MAPK signaling pathway in injured mouse spinal cord tissue and in LPS-treated BV2 cells, and its inhibitory effect was comparable to that of Osimertinib.@*CONCLUSION@#In rat models of SCI, treatment with Ace can inhibit microglia-mediated inflammatory response by regulating the EGFR/MAPK pathway, thus promoting tissue repair and motor function recovery.


Subject(s)
Mice , Animals , Rats , Recovery of Function , Lipopolysaccharides , Microglia , Molecular Docking Simulation , Spinal Cord Injuries , Signal Transduction , Cytokines , ErbB Receptors
9.
Acta Pharmaceutica Sinica B ; (6): 577-597, 2023.
Article in English | WPRIM | ID: wpr-971714

ABSTRACT

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease affecting both upper and lower motor neurons (MNs) with large unmet medical needs. Multiple pathological mechanisms are considered to contribute to the progression of ALS, including neuronal oxidative stress and mitochondrial dysfunction. Honokiol (HNK) has been reported to exert therapeutic effects in several neurologic disease models including ischemia stroke, Alzheimer's disease and Parkinson's disease. Here we found that honokiol also exhibited protective effects in ALS disease models both in vitro and in vivo. Honokiol improved the viability of NSC-34 motor neuron-like cells that expressed the mutant G93A SOD1 proteins (SOD1-G93A cells for short). Mechanistical studies revealed that honokiol alleviated cellular oxidative stress by enhancing glutathione (GSH) synthesis and activating the nuclear factor erythroid 2-related factor 2 (NRF2)-antioxidant response element (ARE) pathway. Also, honokiol improved both mitochondrial function and morphology via fine-tuning mitochondrial dynamics in SOD1-G93A cells. Importantly, honokiol extended the lifespan of the SOD1-G93A transgenic mice and improved the motor function. The improvement of antioxidant capacity and mitochondrial function was further confirmed in the spinal cord and gastrocnemius muscle in mice. Overall, honokiol showed promising preclinical potential as a multiple target drug for ALS treatment.

10.
Article in Chinese | WPRIM | ID: wpr-932372

ABSTRACT

Objective:To investigate the value of Breast Ultrasound Report and Data System (BI-RADS) classification in diagnosis of special types of breast cancer.Methods:A total of 112 patients with special type of breast cancer (112 breast lesions) confirmed by pathology were analyzed by using BI-RADS ultrasound category in the Second Affiliated Hospital, Zhejiang University School of Medicine from August 2009 to August 2020. All patients underwent ultrasound before surgery. The breast lesions were evaluated by senior attending and junior resident according to BI-RADS ultrasound category respectively. Taking histopathological result as the gold standard, the sensitivity and accuracy of BI-RADS classification in the diagnosis of special types of breast cancer were calculated.The differences between different special types of breast cancer in terms of ultrasound characteristics and pathological features were analyzed. Kappa consistency test was used to evaluated the consistency of the results of two physicians.Results:In the 112 patients, pathological results showed that there were 20 cases of metaplastic carcinoma, 19 cases of invasive carcinoma with medullary features, 16 cases of differentiated carcinoma of apocrine gland, 12 cases of mucinous carcinoma, 12 cases of invasive micropapillary carcinoma, 10 cases of invasive papillary carcinoma, 6 cases of invasive lobular carcinoma and 17 cases of other special types of carcinoma. Among them, 4 cases (3.5%) were BI-RADS 3, 13 cases (11.6%) were BI-RADS 4a, 42 cases (37.5%) were BI-RADS 4b, 47 cases (42.0%) were BI-RADS 4c and 6 cases (5.4%) were BI-RADS 5. The accuracy and sensitivity of BI-RADS classification in diagnosis of special types of breast cancer was 96.43% and 96.43%, respectively. There was significant difference in BI-RADS grade among different special types of breast cancer ( P<0.05). Most lesions were characterized by hypoechoic with irregular shape and angular or microlobulated margin. The nodule size, boundary, echo and posterior echo in breast cancer with different special types showed significant differences (all P<0.05). There was a good consistency between the two physicians (Kappa=0.789). Conclusions:The ultrasonography features of different special types of breast cancer are different. BI-RADS classification has great value in diagnosis of special types of breast cancer.

11.
Article in Chinese | WPRIM | ID: wpr-931129

ABSTRACT

Objective:To retrospectively analyze the treatment of 25 cases of lower necrotizing fasciitis.Methods:A total of 25 patients with lower limb necrotizing fasciitis (13 males and 12 females), with mean age 63 years old (48-75 years old) in Dalian Municipal Central Hospital from September 2016 to December 2020. After admission, the patient′s general physical condition was strictly evaluated, the relevant preoperative examination was improved, and the necrotizing fasciitis laboratory risk index (LRINEC) score was performed. In the absence of surgical contraindication, multiple debridement was performed, leaving the necrotic tissue removed for general bacterial culture and drug sensitivity test in parallel. After debridement, eight patients showed a large area of skin necrosis, and amputation was selected. The other 17 patients chose limb protection treatment after debridement, and adopted debridement and free skin grafting. After surgery, patients were encouraged to strengthen rehabilitation exercise to restore limb function to the maximum extent.Results:With followed up 0.6 to 3.0 years, with an average of 1.8 years. Methods include outpatient return visit, WeChat contact or telephone inquiry. The skin survived in 17 patients with mean healing time (27.5 ± 6.9) d. Eighteen patients were multiple bacterial infections and seven patients were single bacterial infections. All patients had no joint dysfunction caused by scar contracture, and reinfection in the skin grafting area.Conclusions:Necrotizing fasciitis requires early diagnosis and early treatment, with correct choice of treatment method is closely related to the patient′s prognosis.

12.
Article in Chinese | WPRIM | ID: wpr-930087

ABSTRACT

Objective:To evaluate the efficacy of Baduanjin combined with mecobalamin tablets in the treatment of type 2 diabetic peripheral neuropathy. Methods:Eighty patients with type 2 diabetic peripheral neuropathy who met the inclusion criteria were randomly divided into two groups with 40 patients in each group ( n=40). The control group took oral mecobalamin tablets and self-management, and the treatment group were treated with Baduanjin on the basis of the control group. All patients were treated for 12 weeks. The clinical symptoms were evaluated by Toronto Clinical Scoring System (TCSS), and the motor nerve conduction velocity (MCV) of tibial nerve and the sensory conduction velocity (SCV) of superficial peroneal nerve were measured by EMG evoked potential instrument. The hemorheological indexes (whole blood low shear viscosity, whole blood high shear viscosity and plasma viscosity) were measured before and after treatment. The clinical efficacy was evaluated and adverse events were recorded. Results:In the course of treatment, 39 patients in each group completed the study with each one dropout. The total effective rate was 87.2% (34/39) in the treatment group and 64.1% (25/39) in the control group. There was significant difference between the two groups ( χ2=5.64, P=0.018). After treatment, the TCSS score of the treatment group was significantly lower than that of the control group ( t=-6.23, P<0.01), the tibial nerve MCV (43.06 ± 4.19 m/s vs. 39.55 ± 4.30 m/s, t=3.65), the superficial peroneal nerve SCV (43.23 ± 4.31 m/s vs. 39.92 ± 3.74 m/s, t=3.62) in the treatment group were significantly higher than the control group ( P<0.001), while the whole blood high shear viscosity, the whole blood low shear viscosity, and the plasma viscosity in the treatment group were significantly lower than the control group ( t value were -10.36, -14.21, -13.88, all Ps<0.001). During the treatment, no serious adverse events occurred in both groups. Conclusion:Baduanjin combined with mecobalamin tablets in the treatment of type 2 diabetic peripheral neuropathy can reduce blood viscosity, promote blood circulation, increase nerve conduction velocity, improve clinical symptoms and signs, and improve clinical efficacy.

13.
Acta Pharmaceutica Sinica ; (12): 1657-1663, 2022.
Article in Chinese | WPRIM | ID: wpr-929454

ABSTRACT

The abnormal lipids metabolism is a critical pathological feature of coronary heart disease (CHD). Additional supplemental intake of polyunsaturated fatty acid (PUFA) has long been considered to be an effective strategy for preventing CHD, but more and more clinical trials have denied this view. Still, it is ambiguity for the specific mechanism of PUFA in CHD. The experimental programs are compliant with ethical principles for animal use and have been approved by the Animal Experiment Ethics Committee of Jinan University. In the present study, we established an animal model by intake of omega-6 PUFA combined acute myocardial ischemia to explore the mechanism of CHD. Intragastric administration of linoleic acid (LA) for 14 days, intraperitoneal injection of isoprenaline (ISO) was applied to induce acute myocardial ischemia for the animal model establishment. The animal ultrasound imaging system was used to detect cardiac function in vivo after ISO injection for 24 h. Serum and heart tissue samples were collected for the myocardial enzyme, phospholipidomics analysis and molecular biological detection. Compared to the LA group, the cardiac function showed that the left ventricular ejection fraction (EF%) and the left ventricular shortening fraction (FS%) decreased, aspaetate aminotransferase (AST), creatine kinase isoenzyme (CK-MB), and lactate dehydrogenase (LDH) increased in the LA + ISO mice. Compared to the ISO group, the phospholipidomics analysis showed that the PUFAs significantly were raised in the LA + ISO myocardium, and the content of oxidized phosphatidylethanolamine (ox-PE) changed most remarkable. Compared with the ISO group, the molecular biology detection showed that glutathione (GSH) and nicotinamide adenine dinucleotide phosphate (NADPH) were depleted, the end-products of ox-PE were increased, and the level of arachidonic acid 12/15-lipoxygenase (ALOX15) protein expression increased obviously. We suggest that ALOX15 mediated phospholipid peroxidation might be the critical mechanism of LA increased the susceptibility of myocardial ischemia injury. This study provides an experimental basis for whether PUFA could be used as an alternative treatment strategy for CHD prevention and provides a new intervention target for the early prevention strategy of CHD.

14.
Acta Pharmaceutica Sinica ; (12): 1544-1556, 2022.
Article in Chinese | WPRIM | ID: wpr-929450

ABSTRACT

Ferroptosis is a novel type of cell death, which is distinguished from the traditional cell death pathways such as apoptosis, proptosis, necrosis and autophagy in terms of morphology, biochemistry and genetics. The main features of ferroptosis are the iron accumulation and lipid peroxidation. The regulation mechanism of ferroptosis involves glutathione metabolism, lipid peroxidation reactions and iron metabolism, which are closely related to the pathological process of tumor, aging, neurodegenerative diseases, ischemia reperfusion injury, cardiovascular and cerebrovascular diseases, kidney injury, hepatic fibrosis and so on. How to effectively study the role of ferroptosis regulation mechanism in the treatment of diseases becomes the hot spot and focus of the ferroptosis research. In recent years, with the in-depth study of ferroptosis, the identification, confirmation and the mechanism of ferroptosis have been developed significantly and have come forth continuously, in the meantime, techniques based on the morphology, biochemistry, molecular biology and genetics have been widely applied in the detection of ferroptosis. In order to deepen readers' understanding of ferroptosis and its detection methods, this paper will mainly review the current research progress on the detection methods and their application in ferroptosis, summarize and discuss their advantages and disadvantages in the detection of ferroptosis, this knowledge are crucial for better understanding and studying the biological function of ferroptosis.

15.
Acta Pharmaceutica Sinica B ; (6): 262-273, 2022.
Article in English | WPRIM | ID: wpr-929292

ABSTRACT

Gastrointestinal mucositis is one of the most debilitating side effects of the chemotherapeutic agent irinotecan (CPT-11). Andrographolide, a natural bicyclic diterpenoid lactone, has been reported to possess anti-colitis activity. In this study, andrographolide treatment was found to significantly relieve CPT-11-induced colitis in tumor-bearing mice without decreasing the tumor suppression effect of CPT-11. CPT-11 causes DNA damage and the release of double-stranded DNA (dsDNA) from the intestine, leading to cyclic-GMP-AMP synthase (cGAS)‒stimulator of interferon genes (STING)-mediated colitis, which was significantly decreased by andrographolide both in vivo and in vitro. Mechanistic studies revealed that andrographolide could promote homologous recombination (HR) repair and downregulate dsDNA‒cGAS‒STING signaling and contribute to the improvement of CPT-11-induced gastrointestinal mucositis. These results suggest that andrographolide may be a novel agent to relieve gastrointestinal mucositis caused by CPT-11.

16.
Acta Pharmaceutica Sinica B ; (6): 149-166, 2022.
Article in English | WPRIM | ID: wpr-929285

ABSTRACT

Colorectal cancer (CRC), a malignant tumor worldwide consists of microsatellite instability (MSI) and stable (MSS) phenotypes. Although SHP2 is a hopeful target for cancer therapy, its relationship with innate immunosuppression remains elusive. To address that, single-cell RNA sequencing was performed to explore the role of SHP2 in all cell types of tumor microenvironment (TME) from murine MC38 xenografts. Intratumoral cells were found to be functionally heterogeneous and responded significantly to SHP099, a SHP2 allosteric inhibitor. The malignant evolution of tumor cells was remarkably arrested by SHP099. Mechanistically, STING-TBK1-IRF3-mediated type I interferon signaling was highly activated by SHP099 in infiltrated myeloid cells. Notably, CRC patients with MSS phenotype exhibited greater macrophage infiltration and more potent SHP2 phosphorylation in CD68+ macrophages than MSI-high phenotypes, suggesting the potential role of macrophagic SHP2 in TME. Collectively, our data reveals a mechanism of innate immunosuppression mediated by SHP2, suggesting that SHP2 is a promising target for colon cancer immunotherapy.

17.
Article in Chinese | WPRIM | ID: wpr-927913

ABSTRACT

The plant growth, development, and secondary metabolism are regulated by R2 R3-MYB transcription factors. This study identified the R2 R3-MYB genes in the genome of Andrographis paniculata and analyzed the chromosomal localization, gene structure, and conserved domains, phylogenetic relationship, and promoter cis-acting elements of these R2 R3-MYB genes. Moreover, the gene expression profiles of R2 R3-MYB genes under abiotic stress and hormone treatments were generated by RNA-seq and validated by qRT-PCR. The results showed that A. paniculata contained 73 R2 R3-MYB genes on 21 chromosomes. These members belonged to 34 subfamilies, 19 of which could be classified into the known subfamilies in Arabidopsis thaliana. The 73 R2 R3-MYB members included 36 acidic proteins and 37 basic proteins, with the lengths of 148-887 aa. The domains, motifs, and gene structures of R2 R3-MYBs in A. paniculata were conserved. The promoter regions of these genes contains a variety of cis-acting elements related to the responses to environmental factors and plant hormones including light, ABA, MeJA, and drought. Based on the similarity of functions of R2 R3-MYBs in the same subfamily and the transcription profiles, ApMYB13/21/35/67/73(S22) may regulate drought stress through ABA pathway; ApMYB20(S11) and ApMYB55(S2) may play a role in the response of A. paniculata to high temperature and UV-C stress; ApMYB5(S7) and ApMYB33(S20) may affect the accumulation of andrographolide by regulating the expression of key enzymes in the MEP pathway. This study provides theoretical reference for further research on the functions of R2 R3-MYB genes in A. paniculata and breeding of A. paniculata varieties with high andrographolide content.


Subject(s)
Andrographis paniculata , Gene Expression Regulation, Plant , Genes, myb , Multigene Family , Phylogeny , Plant Proteins/metabolism
18.
Article in English | WPRIM | ID: wpr-926045

ABSTRACT

Objective@#: The clinical management paradigm of skull base chordomas is still challenging. Surgical resection plays an important role of affecting the prognosis. Endonasal endoscopic approach (EEA) has gradually become the preferred surgical approach in most cases, but traditional transcranial surgery cannot be completely replaced. This study presents a comparison of the results of the two surgical strategies and a summary of the treatment algorithms for skull base chordomas. @*Methods@#: We retrospectively analyzed the surgical outcomes and follow-up data of 48 patients with skull base chordomas diagnosed pathologically who received transnasal midline approaches (TMA) and transcranial lateral approaches (TLA) from 2010 to 2020. @*Results@#: Among the 48 patients, 36 cases were adopted TMA and 12 cases were performed with TLA. In terms of gross total resection (GTR) rate, 27.8% in TMA and 16.7% in TLA and with EEA alone it was increased to 38.9%, while 29.7% in primary surgery. In TMA, the cerebrospinal fluid (CSF) leak remains the most common complication (13 cases, 36.1%), other main complications included death, cranial nerve palsy, hypopituitarism, all the comparisons were no statistical significance. The Karnofsky Performance Scale scores in TMA were all better than those in TLA at different time, and the overall survival (OS) and recurrence free survival/progression free survival was just the reverse. @*Conclusion@#: The EEA for skull base chordomas resection has improved the GTR rate, but transcranial approach is still an alternative approach. It is necessary to select an appropriate surgical approach based on the location and the pattern of tumor growth in order to obtain the best surgical outcomes.

19.
Acta Pharmaceutica Sinica ; (12): 1273-1281, 2022.
Article in Chinese | WPRIM | ID: wpr-924739

ABSTRACT

Colorectal cancer is a common malignant tumor of digestive tract, and the risk of inflammatory bowel disease developing into colorectal cancer is significantly increased. Immune signaling pathways NF-κB, IL-6/STAT3, COX-2/PGE2, IL-23/Th17 and TLRs have been confirmed to promote the transformation from colitis to colorectal cancer. NOD2 and intestinal microbes also participate in the regulation of inflammation mediated carcinogenesis. Chronic inflammation is a potential risk for colorectal cancer, and anti-inflammatory drugs may play a chemical preventive role. In this review, we summarize the signaling pathways involved in inflammation-associated colon carcinogenesis and evaluate the chemoprophylaxis of colon cancer.

20.
Chinese Journal of Burns ; (6): 347-353, 2022.
Article in Chinese | WPRIM | ID: wpr-936017

ABSTRACT

Objective: To observe the clinical effects of free latissimus dorsi myocutaneous flap combined with artificial dermis and split-thickness skin graft in the treatment of degloving injury in lower limbs. Methods: A retrospective observational study was conducted. From December 2017 to December 2020, 8 patients with large skin and soft tissue defect caused by degloving injury in lower extremity were admitted to Ningbo No.6 Hospital, including 5 males and 3 females, aged from 39 to 75 years, with wound area of 25 cm×12 cm-61 cm×34 cm. The free latissimus dorsi myocutaneous flap with latissimus dorsi muscle in the width of 12-15 cm and flap area of 20 cm×8 cm-32 cm×8 cm was used to repair the skin and soft tissue defect of bone/tendon exposure site or functional area. The other defect was repaired with bilayer artificial dermis, and the flap donor site was sutured directly. After the artificial dermis was completely vascularized, the split-thickness skin graft from thigh was excised and extended at a ratio of 1∶2 to 1∶4 and then transplanted to repair the residual wound, and the donor site of skin graft was treated by dressing change. The survival of latissimus dorsi myocutaneous flap, artificial dermis, and split-thickness skin graft after operation was observed, the interval time between artificial dermis transplantation and split-thickness skin graft transplantation was recorded, and the healing of donor site was observed. The appearance and function of operative area were followed up. At the last outpatient follow-up, the sensory recovery of flap was evaluated by British Medical Research Council evaluation criteria, the flap function was evaluated by the comprehensive evaluation standard of flap in Operative Hand Surgery, the scar of lower limb skin graft area and thigh skin donor area was evaluated by Vancouver scar scale, and the patient's satisfaction with the curative effects was asked. Results: The latissimus dorsi myocutaneous flap survived in 6 patients, while the distal tip of latissimus dorsi myocutaneous flap was partially necrotic in 2 patient and was repaired by skin grafting after resection at split-thickness skin grafting. The artificial dermis survived in all 8 patients after transplantation. The split-thickness skin graft survived in 7 patients, while partial necrosis of the split-thickness skin graft occurred in one patient and was repaired by skin grafting again. The interval time between artificial dermis transplantation and split-thickness skin graft transplantation was 15-26 (20±5) d. The donor site of latissimus dorsi myocutaneous flap healed with linear scar after operation, and the thigh skin graft donor site healed with scar after operation. The patients were followed up for 6-18 (12.5±2.3) months. The color and elasticity of the flap were similar to those of the surrounding skin tissue, and the lower limb joint activity returned to normal. There was no increase in linear scar at the back donor site or obvious hypertrophic scar at the thigh donor site. At the last outpatient follow-up, the sensation of the flap recovered to grade S2 or S3; 3 cases were excellent, 4 cases were good, and 1 case was fair in flap function; the Vancouver scar scale score of lower limb skin graft area was 4-7 (5.2±0.9), and the Vancouver scar scale score of thigh skin donor area was 1-5 (3.4±0.8). The patients were fairly satisfied with the curative effects. Conclusions: In repairing the large skin and soft tissue defect from degloving injury in lower extremity, to cover the exposed bone/tendon or functional area with latissimus dorsi myocutaneous flap and the residual wound with artificial dermis and extended split-thickness skin graft is accompanied by harvest of small autologous flap and skin graft, good recovery effect of functional area after surgery, and good quality of healing in skin grafted area.


Subject(s)
Female , Humans , Male , Cicatrix/surgery , Degloving Injuries/surgery , Dermis/surgery , Lower Extremity/surgery , Mammaplasty , Myocutaneous Flap , Plastic Surgery Procedures , Skin Transplantation , Soft Tissue Injuries/surgery , Superficial Back Muscles/surgery , Treatment Outcome
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