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1.
Chinese Journal of Medical Instrumentation ; (6): 351-354, 2023.
Article in Chinese | WPRIM | ID: wpr-982244

ABSTRACT

OBJECTIVE@#The national requirements for the fund management of scientific research projects are becoming more stringent, so that it is convenient to carry out scientific research work and can strengthen the regulation of scientific research reagent procurement, so this study explores the standardization of the whole process of the procurement of scientific research reagent supplies in hospitals and new modes of management.@*METHODS@#By exploring the implementation of the centralized procurement management platform, we engage in full process supervision before, during, and after the event.@*RESULTS@#Introduction of centralized procurement management platform for scientific research reagent supplies can normalize the procurement process, ensure the quality of procurement and improve the procurement efficiency on the basis of ensuring the quality of scientific research.@*CONCLUSIONS@#The new model of centralized procurement of full process management based on one-stop service for scientific research reagent supplies is an important part of improving the fine scale management of public hospitals, and it is of great significance in improving the level of scientific research in China and avoiding scientific research corruption.


Subject(s)
Indicators and Reagents , Hospitals, Public , China
2.
Chinese Journal of Medical Genetics ; (6): 727-732, 2023.
Article in Chinese | WPRIM | ID: wpr-981816

ABSTRACT

OBJECTIVE@#To carry out optical genome mapping (OGM) for a Chinese pedigree with a rare paracentric reverse insertion of chromosome 17.@*METHODS@#A high-risk pregnant woman identified at the Prenatal Diagnosis Center of Hangzhou Women's Hospital in October 2021 and her family members were selected as the study subjects. Chromosome G banding analysis, fluorescence in situ hybridization (FISH), single nucleotide polymorphism array (SNP array) and OGM were applied to verify the balanced structural abnormality of chromosome 17 in the pedigree.@*RESULTS@#Chromosomal karyotyping analysis and SNP array assay have identified a duplication of 17q23q25 in the fetus. Karyotyping analysis of the pregnant woman showed that the structure of chromosome 17 was abnormal, whilst SNP array has detected no abnormality. OGM revealed that the woman has carried a paracentric reverse insertion, which was confirmed by FISH. The karyotype of her husband was normal.@*CONCLUSION@#The duplication of 17q23q25 in the fetus has derived from a paracentric reverse insertion of chromosome 17 in its mother. OGM has the advantage for delineating balanced chromosome structural abnormalities.


Subject(s)
Pregnancy , Humans , Female , Pedigree , In Situ Hybridization, Fluorescence , Chromosomes, Human, Pair 17/genetics , East Asian People , Chromosome Aberrations , Prenatal Diagnosis , Chromosome Mapping , Chromosome Inversion
3.
China Journal of Orthopaedics and Traumatology ; (12): 676-685, 2023.
Article in Chinese | WPRIM | ID: wpr-981755

ABSTRACT

OBJECTIVE@#To compare the clinical efficacy of screw and bone plate internal fixation in the treatment of Lisfranc injury.@*METHODS@#The databases of Wanfang, CNKI, Pubmed, EMBASE, VIP, BIOSIS and other databases were retrieved by computer, and the clinical trial literature from January 1, 2000 to August 1, 2021 was retrieved, the methodological quality of the included studies was strictly evaluated and the data were extracted, and the obtained data were meta-analyzed by Revman 5.4 software.@*RESULTS@#Nine randomized controlled trial literature and 10 retrospective cohort studies were included, of which 416 patients in the experimental group were treated with screw internal fixation, and 435 patients in the control group were treated with bone plate internal fixation. Meta-analysis showed that the surgical time of the bone plate internal fixation group was longer than that of the screw internal fixation group [MD=-14.40, 95%CI(-17.21, -11.60), P<0.000 01], the postoperative X-ray anatomical reduction of the bone plate internal fixation group [MD=0.47, 95%CI(0.25, 0.86), P=0.01], the excellent and good rate of postoperative American orthopedic foot and ankle society(AOFAS) foot function score[MD=0.25, 95%CI(0.15, 0.42), P<0.000 01], postoperative AOFAS foot function score [MD=-5.51, 95%CI(-10.10, -0.92), P=0.02] of the bone plate fixation group was better than those of the screw internal fixation group. Two kinds of operation method had no statistical different for postoperative fracture healing time[MD=1.91, 95%CI(-1.36, 5.18), P=0.25], postoperative visual analgue scale(VAS)[MD=0.38, 95%CI(0.09, 0.86), P=0.11], postoperative complications [MD=1.32, 95%CI(0.73, 2.40), P=0.36], the postoperative infection [MD=0.84, 95%CI(0.48, 1.46), P=0.53], the postoperative fracture internal fixation loosening [MD=1.25, 95% CI(0.61, 2.53), P=0.54], the postoperative incidence of traumatic arthritis [MD=1.80, 95%CI(0.83, 3.91), P=0.14].@*CONCLUSION@#Bone plate fixation has better short-term and medium-term results and lower reoperation rate in the treatment of Lisfranc injury, so it is recommended to use bone plate fixation in the treatment of Lisfranc injury.


Subject(s)
Humans , Bone Plates , Retrospective Studies , Fractures, Bone/surgery , Fracture Fixation, Internal/methods , Bone Screws , Treatment Outcome , Postoperative Complications
4.
China Journal of Orthopaedics and Traumatology ; (12): 591-596, 2023.
Article in Chinese | WPRIM | ID: wpr-981739

ABSTRACT

The shoulder joint is the most flexible joint in the body with the largest range of motion, and the movement pattern is more complex. Accurate capture of three-dimensional motion data of the shoulder joint is crucial for biomechanical evaluation. Optical motion capture systems offer a non-invasive and radiation-free method to capture shoulder joint motion data during complex movements, enabling further biomechanical analysis of the shoulder joint. This review provides a comprehensive overview of optical motion capture technology in the context of shoulder joint movement, including measurement principles, data processing methods to reduce artifacts from skin and soft tissues, factors influencing measurement results, and applications in shoulder joint disorders.


Subject(s)
Humans , Shoulder , Motion Capture , Biomechanical Phenomena , Upper Extremity , Shoulder Joint , Movement , Range of Motion, Articular
5.
Chinese Journal of Cardiology ; (12): 722-730, 2023.
Article in Chinese | WPRIM | ID: wpr-984710

ABSTRACT

Objective: To reveal the similarities and differences in myocardial metabolic characteristics between heart failure with preserved ejection fraction (HFpEF) and heart failure with reduced ejection fraction (HFrEF) mice using metabolomics. Methods: The experimental mice were divided into 4 groups, including control, HFpEF, sham and HFrEF groups (10 mice in each group). High fat diet and Nω-nitroarginine methyl ester hydrochloride (L-NAME) were applied to construct a"two-hit"HFpEF mouse model. Transverse aortic constriction (TAC) surgery was used to construct the HFrEF mouse model. The differential expression of metabolites in the myocardium of HFpEF and HFrEF mice was detected by untargeted metabolomics (UHPLC-QE-MS). Variable importance in projection>1 and P<0.05 were used as criteria to screen and classify the differentially expressed metabolites between the mice models. KEGG functional enrichment and pathway impact analysis demonstrated significantly altered metabolic pathways in both HFpEF and HFrEF mice. Results: One hundred and nine differentially expressed metabolites were detected in HFpEF mice, and 270 differentially expressed metabolites were detected in HFrEF mice. Compared with the control group, the most significantly changed metabolite in HFpEF mice was glycerophospholipids, while HFrEF mice presented with the largest proportion of carboxylic acids and their derivatives. KEGG enrichment and pathway impact analysis showed that the differentially expressed metabolites in HFpEF mice were mainly enriched in pathways such as biosynthesis of unsaturated fatty acids, ether lipid metabolism, amino sugar and nucleotide sugar metabolism, glycerophospholipid metabolism, arachidonic acid metabolism and arginine and proline metabolism. The differentially expressed metabolites in HFrEF mice were mainly enriched in arginine and proline metabolism, glycine, serine and threonine metabolism, pantothenate and CoA biosynthesis, glycerophospholipid metabolism, nicotinate and nicotinamide metabolism and arachidonic acid metabolism, etc. Conclusions: HFpEF mice have a significantly different myocardial metabolite expression profile compared with HFrEF mice. In addition, biosynthesis of unsaturated fatty acids, arachidonic acid metabolism, glycerophospholipid metabolism and arginine and proline metabolism are significantly altered in both HFpEF and HFrEF mice, suggesting that these metabolic pathways may play an important role in disease progression in both types of heart failure.


Subject(s)
Mice , Animals , Heart Failure/metabolism , Stroke Volume , Chromatography, Liquid , Tandem Mass Spectrometry , Metabolomics , Arachidonic Acids , Proline
6.
Cancer Research on Prevention and Treatment ; (12): 721-725, 2023.
Article in Chinese | WPRIM | ID: wpr-985868

ABSTRACT

Nowadays, angiogenesis has gradually become one of the most popular research directions of cancer since Jodah Folkman put forward a theory about that tumor development needs angiogenesis. Meanwhile, relevant research methods are enriched step by step. In this paper, we have made a systematic review to provide methodological references for subsequent studies about tumor angiogenesis and antiangiogenic therapy.

7.
Chinese Journal of Surgery ; (12): 777-783, 2023.
Article in Chinese | WPRIM | ID: wpr-985822

ABSTRACT

Objective: To investigate the influence of extending the waiting time on tumor regression after neoadjuvant chemoradiology (nCRT) in patients with locally advanced rectal cancer (LARC). Methods: Clinicopathological data from 728 LARC patients who completed nCRT treatment at the First Affiliated Hospital, Naval Medical University from January 2012 to December 2021 were collected for retrospective analysis. The primary research endpoint was the sustained complete response (SCR). There were 498 males and 230 females, with an age (M(IQR)) of 58 (15) years (range: 22 to 89 years). Logistic regression models were used to explore whether waiting time was an independent factor affecting SCR. Curve fitting was used to represent the relationship between the cumulative occurrence rate of SCR and the waiting time. The patients were divided into a conventional waiting time group (4 to <12 weeks, n=581) and an extended waiting time group (12 to<20 weeks, n=147). Comparisons regarding tumor regression, organ preservation, and surgical conditions between the two groups were made using the t test, Wilcoxon rank sum test, or χ2 test as appropriate. The Log-rank test was used to elucidate the survival discrepancies between the two groups. Results: The SCR rate of all patients was 21.6% (157/728). The waiting time was an independent influencing factor for SCR, with each additional day corresponding to an OR value of 1.010 (95%CI: 1.001 to 1.020, P=0.031). The cumulative rate of SCR occurrence gradually increased with the extension of waiting time, with the fastest increase between the 9th to <10th week. The SCR rate in the extended waiting time group was higher (27.9%(41/147) vs. 20.0%(116/581), χ2=3.901, P=0.048), and the organ preservation rate during the follow-up period was higher (21.1%(31/147) vs. 10.7%(62/581), χ2=10.510, P=0.001). The 3-year local recurrence/regrowth-free survival rates were 94.0% and 91.1%, the 3-year disease-free survival rates were 76.6% and 75.4%, and the 3-year overall survival rates were 95.6% and 92.2% for the conventional and extended waiting time groups, respectively, with no statistical differences in local recurrence/regrowth-free survival, disease-free survival and overall survival between the two groups (χ2=1.878, P=0.171; χ2=0.078, P=0.780; χ2=1.265, P=0.261). Conclusions: An extended waiting time is conducive to tumor regression, and extending the waiting time to 12 to <20 weeks after nCRT can improve the SCR rate and organ preservation rate, without increasing the difficulty of surgery or altering the oncological outcomes of patients.

8.
Chinese Journal of Surgery ; (12): 467-473, 2023.
Article in Chinese | WPRIM | ID: wpr-985785

ABSTRACT

Intrahepatic cholangiocarcinoma (ICC) is the second most common primary malignant tumor in the liver after hepatocellular carcinoma. Its incidence and mortality rates have increased worldwide in recent years. Surgical resection is the best treatment modality for ICC;however,the overall prognosis remains poor. Accurate evaluation of post operative prognosis allows personalized treatment and improved long-term outcomes of ICC. The American Joint Commission on Cancer TNM staging manual is the basis for the standardized diagnosis and treatment of ICC;however,the contents of stage T and stage N need to be improved. The nomogram model or scoring system established in the analysis of commonly used clinicopathological parameters can provide individualized prognostic evaluation and improve prediction accuracy;however,more studies are needed to validate the results before clinical use. Meanwhile,imaging features exhibit great potential to establish the post operative prognosis evaluation system for ICC. Molecular-based classification provides an accurate guarantee for prognostic assessment as well as selection of populations that are sensitive to targeted therapy or immunotherapy. Therefore,the establishment of a prognosis evaluation system,based on clinical and pathological characteristics and centered on the combination of multidisciplinary and multi-omics,will be conducive to improving the long-term outcomes of ICC after surgical resection in the context of big medical data.


Subject(s)
Humans , Bile Ducts, Intrahepatic/pathology , Cholangiocarcinoma/pathology , Prognosis , Liver Neoplasms/surgery , Bile Duct Neoplasms/pathology
9.
Chinese Journal of Pathology ; (12): 599-605, 2023.
Article in Chinese | WPRIM | ID: wpr-985739

ABSTRACT

Objective: To investigate the clinicopathological and molecular features of primary cardiac angiosarcoma (PCAS), and to analyze the correlation between KDR mutation and the clinicopathological features of PCAS. Methods: Thirteen cases of PCAS were collected at Beijing Anzhen Hospital, Capital Medical University from January 2007 to December 2021. The clinicopathological features, diagnosis, differential diagnosis and outcome were retrospectively analyzed. KDR mutation was detected by next-generation sequencing (NGS) and then the expression of KDR (VEGFR2) was determined by immunohistochemistry (IHC), with review of relevant literatures. Results: There were eight males and five females with a mean age of 45 years. The primary tumor was in the right atrium in 10 cases, left atrium in two cases and right ventricle in one case. The histomorphology was mainly poorly differentiated angiosarcoma (11 cases), with highly pleomorphic spindle or round cells in solid sheets, brisk mitotic activity and extensive necrosis. Vascular lumen formation was observed in two cases of high to moderate differentiation, and biphenotypic differentiation was seen in five cases. IHC staining showed CD34, CD31, Fli1, ERG and vimentin were diffusely positive, pan-cytokeratin was positive, Ki-67 index ranged from 3% to 90%, which was positively correlated with the differentiation degree and grade of the PCASs (P<0.05). At the end of follow-up period, one patient was alive, two patients were lost to follow-up, and the remaining 10 patients had an average survival time of 4.6 months. Finally, NGS sequencing was performed on seven samples after screening, and the results showed that KDR and NF1 mutations were both present in three cases. VEGFR2 expression had no significant correlation with the differentiation degree and grade of PCAS (P>0.05), and it was not related to KDR mutation. Conclusions: PCASs mainly occur in the right atrium, and are mainly poorly differentiated. Ki-67 index is helpful to assess the degree and grade of tumor differentiation. The occurrence and development of PCAS may be related to the pathway involved in KDR mutation, but KDR mutation has no clear correlation with clinicopathological characteristics of PCAS, and immunohistochemical staining can not replace gene detection to determine whether the tumor had KDR mutation.


Subject(s)
Male , Female , Humans , Middle Aged , Hemangiosarcoma/genetics , Retrospective Studies , Ki-67 Antigen , Immunohistochemistry , Molecular Biology , Biomarkers, Tumor/analysis
10.
Chinese Journal of Epidemiology ; (12): 705-712, 2023.
Article in Chinese | WPRIM | ID: wpr-985551

ABSTRACT

Cardiovascular disease (CVD) is the leading cause of mortality and healthy life expectancy loss, ranking first in causing the global burden of disease. In addition to the traditional CVD risk factors, such as hypertension and diabetes, environmental chemical pollutants may also play a role in the development of CVD. This paper summarizes the evidence regarding the relation of exposures to metal or metalloid and persistent organic pollutants with risk for CVD and introduces the research progress in the relation between the exposures to two environmental chemical pollutants and CVD risk. The study aims to provide scientific evidence for the effective prevention of CVD through the management of chemical pollutants in environment.


Subject(s)
Humans , Cardiovascular Diseases , Persistent Organic Pollutants , Metalloids , Hypertension , Environmental Pollutants
11.
International Eye Science ; (12): 668-671, 2023.
Article in Chinese | WPRIM | ID: wpr-965798

ABSTRACT

AIM: To investigate the clinical efficacy and safety of ultrasonic ciliary plasty(UCP)combined with injection of anti-vascular endothelial growth factor(VEGF)in the treatment of neovascular glaucoma(NVG).METHODS: A total of 30 NVG patients(30 eyes)admitted to the First Affiliated Hospital of Bengbu Medical College from September 2020 to September 2021 were selected. After admission, all the eyes of the patients were injected with anti-VEGF drug(ranibizumab). After surgery, 15 patients were randomly selected for UCP treatment(UCP group), and the other 15 patients received trabeculectomy(trabeculectomy group). During the 10mo postoperative follow-up, the decrease of intraocular pressure was compared between the two groups and the changes of the degree of ocular pain and the occurrence of related complications were evaluated at each follow-up visit.RESULTS: The intraocular pressure and pain degree of the UCP and trabeculectomy groups were significantly lower than those before operation, and the complication probability of the UCP group was less than that of the trabeculectomy group.CONCLUSION: With fewer complications and high safety, UCP combined with anti-VEGF injection can effectively control intraocular pressure and pain in NVG patients.

12.
International Eye Science ; (12): 425-429, 2023.
Article in Chinese | WPRIM | ID: wpr-964242

ABSTRACT

ArcScan Insight 100 very high-frequency(VHF)digital ultrasound scanner is a new ocular ultrasonic measuring instrument, which can detect and measure the anterior segment. It can be used for screening before corneal refractive surgery and follow-up after corneal refractive surgery, measuring anterior segment parameters before implantable collamer lens(ICL)implantation, predicting preoperative vault, measuring postoperative vault, early screening keratoconus, and diagnosing glaucoma, cataract and eye injuries, etc. Taking the advantages of a wide range examination of ultrasound biomicroscope(UBM)and simple operation of optical coherence tomography(OCT), it has a broad prospect for clinical application. In this paper, the measurement principle, application method, parameters and clinical application progress of ArcScan Insight 100 VHF digital ultrasound scanner are reviewed in detail.

13.
International Eye Science ; (12): 356-362, 2023.
Article in Chinese | WPRIM | ID: wpr-964229

ABSTRACT

AIM: To analyze the characteristics and correlated risk factors of dry eye patients with corneal epithelial defects.METHODS: Outpatient medical records of dry eye patients with corneal epithelial defects at Peking University Third Hospital from July 2018 to June 2019 were retrospectively analyzed. The patients' data including sex, age, visit date, presence of comorbidities, and meteorological indicators at the same period were statistically analyzed.RESULTS: A total of 291 dry eye patients with corneal epithelial defects, of whom 75.3% were female, were retrospectively analyzed. Young patients aged 21-30 made up the most(26.5%), while the proportion of teenagers(<18 years, 5.8%)and the elderly(≥61 years, 17.2%)was low. However, as the largest proportion of this population, young and middle-aged patients tend to experience fewer visits(5.4±12.4). Spring and winter were the main seasons of complaints. The meteorological indicators at the same period including fine-particulate matter with a median aerometric diameter of less than 10μm(PM10), sulfur dioxide(SO2), nitrogen dioxide(NO2), and reduced average relative humidity were found significantly correlated with dry eye corneal epithelial defects(P<0.05). Conjunctivitis, cataracts, blurred vision, and trichiasis ranked the top four comorbidities.CONCLUSION: Dry eye corneal epithelial defects of young and female population cannot be ignored. PM10, SO2, NO2, and reduced humidity are found significantly correlated with dry eye corneal epithelial defects. For dry eye patients with conjunctivitis, cataracts, blurred vision, and trichiasis, more attention should be paid to their corneal conditions.

14.
Chinese Journal of General Surgery ; (12): 280-286, 2023.
Article in Chinese | WPRIM | ID: wpr-994571

ABSTRACT

Objective:To probe into the potential prognostic value of lymphocyte subsets in gastric cancer.Methods:This study included patients who underwent radical gastrectomy for gastric cancer from Aug 2014 to Dec 2016. The immunological differences was analyzed in different infiltration patterns. The overall survival of patients was analyzed by Kaplan-Meier method and Log-rank test. COX regression was performed to assess independent prognostic factors of the patients, and finally constructed nomogram.Results:The median number of peripheral CD4 and CD19 cells in infiltration pattern c was 750 (94-2 504) cells/μl and 186 (17-820) cells/μl; the median number of peripheral CD4 and CD19 cells in infiltration pattern a was 802 (203-2 071) cells/μl and 213 (5-948) cells/μl, the number of peripheral CD4,CD19 cells in infiltration pattern c was lower than that in infiltration pattern a, with statistically significant differences (CD4: Z=-3.061, P=0.002; CD19: Z=-2.016 , P=0.044). CD19 lymphocytes ( P=0.023) were associated with infiltration pattern a, CD8 lymphocytes ( P=0.027) were associated with infiltration pattern b, and CD4 lymphocytes ( P=0.026) were independent risk factors associated with the prognosis of infiltration pattern c. A nomogram can be constructed to evaluate the prognosis of patients. Conclusion:There are differences in the number of peripheral lymphocyte subsets in patients with different INF types. A nomogram can be constructed from lymphocyte subsets and clinicopathological features to assess patient prognosis.

15.
Chinese Journal of General Surgery ; (12): 253-257, 2023.
Article in Chinese | WPRIM | ID: wpr-994566

ABSTRACT

Objective:To compare the prognosis difference between proximal gastrectomy (PG) and total gastrectomy (TG) in patients with advanced upper gastric cancer.Methods:This study included patients of upper gastric cancer admitted from Jan 2011 to Dec 2016 undergoing radical resection at Harbin Medical University Cancer Hospital. Patients were divided into TG group (178 cases) and PG group (185 cases).Results:Comapared to PG group , more TG patients were with tumor diameter >4 cm, Borrmann type Ⅲ and postoperative stage Ⅲ ( χ2=9.687, P=0.002; χ2=24.897, P=0.001; χ2=6.257 P=0.044).The 5-year overall survival (OS) of the PG group and the TG group were 64.3% (95% CI: 45.1%-50.5%) and 60.6% (95% CI: 41.3%-47.6%) ( P=0.297).After propensity score matching, the OS between the two groups was not statistically significant ( P=0.876).Subgroup analysis of chemotherapy showed that the difference in survival between TG group and PG group was not statistically significant ( P=0.309). Conclusion:There was no difference in survival between PG and TG in patients with advanced upper gastric cancer.

16.
Chinese Journal of Endocrinology and Metabolism ; (12): 345-352, 2023.
Article in Chinese | WPRIM | ID: wpr-994332

ABSTRACT

Objective:To identify the genetic variation in a mucopolysaccharidosis type Ⅱ(MPS Ⅱ)family, and conduct a functional study of iduronate-2-sulfatase(IDS): c.323A>C.Methods:A five-generation MPS Ⅱ family of 83 individuals including 4 patients from northern China was collected. Urine mucopolysaccharide and Alder-Reilly body were tested to assist the clinical diagnosis of MPS Ⅱ. IDS enzyme activity was detected on core family members. By the whole exome sequencing of a MPS Ⅱ patient in this family and bioinformatics analysis, the variant was screened and further identified by PCR-Sanger sequencing. Finally, to validate the function of the variant in vitro, the wild-type IDS overexpression plasmid(pCMV-hIDS-WT)and the IDS overexpression plasmid carrying the mutation site(pCMV-hIDS-c.323A>C)were transfected into COS-7 cells and the IDS activity was detected. Results:The proband(Ⅳ3)and Ⅳ4 were diagnosed as MPS Ⅱ by urine mucopolysaccharide, Alder-Reilly body, and IDS enzyme activity tests. Ⅳ3, Ⅳ4, Ⅲ19, and Ⅲ32 were determined to carry IDS: c.323A>C missense variant through the whole-exome sequencing, and diagnosed as MPS Ⅱ. Meanwhile, Ⅱ2, Ⅱ4, Ⅱ8, Ⅱ12, Ⅱ14, Ⅲ5, Ⅲ7, Ⅳ14 in the MPS Ⅱ family carried IDS: c.323A>C missense variant, and were excluded as MPS Ⅱ. The in vitro experiment in COS-7 cells showed that the missense mutation led to a significant decrease in IDS enzyme activity. Conclusion:The variant IDS: c.323A>C: p.Y108S significantly decreases the activity of IDS enzyme in vivo and in vitro, and it is identified as a pathogenic variant for MPS Ⅱ.

17.
Chinese Journal of Nuclear Medicine and Molecular Imaging ; (6): 470-474, 2023.
Article in Chinese | WPRIM | ID: wpr-993620

ABSTRACT

Objective:To investigate the efficacy and safety of anlotinib in distant metastatic radioactive iodine-refractory differentiated thyroid cancer (RAIR-DTC).Methods:Retrospective analysis was performed on 17 patients with distant metastatic RAIR-DTC (6 males, 11 females, age: 57.0(45.5, 63.0) years) from Affiliated Hospital of Qingdao University between October 2018 and February 2023, including 13 patients receiving first-line treatment and 4 patients receiving second-line treatment with anlotinib. The changes of serum thyroglobulin (Tg) during the treatment of anlotinib, the changes of maximum diameter of the target lesion at the last follow-up compared with the diameter at baseline, the imaging efficacy, and treatment-related adverse events were analyzed. The serological and imaging effects of the first-line treatment group and the second-line treatment group were compared. The Fisher exact test was used to analyze the differences between groups.Results:The follow-up time of 17 patients was 17.3(9.5, 21.4) months, and the objective response rate (ORR) and disease control rate (DCR) were 7/17 and 16/17, respectively. There were no significant differences of ORR (6/13 vs 1/4; P=0.603) and DCR (13/13 vs 3/4; P=0.235) between the first-line and second-line treatment groups. The change rates of serum Tg at 3, 6 weeks and the last follow-up were -30.2%(-61.2%, -15.5%), -64.8%(-90.6%, -32.3%), and -85.8%(-96.1%, -50.7%), respectively. At the last follow-up, the change rate of maximum diameter of target lesions was -20.0%(-45.0%, -5.2%). The incidence of treatment-related adverse reactions was 14/17, and 2 patients (2/17) had grade 3 or above adverse reactions. Conclusion:Anlotinib shows superior efficacy with tolerable toxicity in the first-line treatment of distant metastatic RAIR-DTC, and hopefully plays an important role in second-line treatment for RAIR-DTC resistant to sorafenib.

18.
Chinese Journal of Nuclear Medicine and Molecular Imaging ; (6): 465-469, 2023.
Article in Chinese | WPRIM | ID: wpr-993619

ABSTRACT

Objective:To investigate the significance of B-Raf proto-oncogene, serine/threonine kinase (BRAF) V600E mutation in the prediction of response to apatinib treatment in advanced radioactive iodine-refractory differentiated thyroid cancer (RAIR-DTC). Methods:Twenty patients (10 males, 10 females, age: 51.5(46.3, 65.0) years) with advanced RAIR-DTC from Peking Union Medical College Hospital between March 2016 and March 2023 were retrospectively enrolled, and all patients were treated with apatinib and underwent genetic sequencing (including BRAF V600E and telomerase reverse transcriptase (TERT) promoter). The serological and imaging data, progression-free survival (PFS) and overall survival (OS) data were collected during apatinib treatment. The Kaplan-Meier survival analysis (log-rank test) was performed, and Mann-Whitney U test were used to analyze the differences of duration of response (DOR) between mutation group and wild-type group. Then univariate and multivariate Cox regression analyses were conducted. Results:The PFS (35.3 vs 9.2 months, χ2=7.53, P=0.006) and DOR (25.8(7.4, 35.2) vs 8.2(2.5, 13.4) months, U=23.00, P=0.046) of the BRAF V600E mutation group were longer than those of the wild-type group. Univariate Cox regression analysis showed that the BRAF V600E mutation group had better PFS benefit (hazard ratio ( HR)=0.22 (95% CI: 0.06-0.72), P=0.013), and the risk of disease progression or death in patients with lung metastasis and bone or brain metastasis was 3.06(95% CI: 1.10-8.54, P=0.033) times higher than that in patients with lung metastasis alone. Further, multivariate cox regression analysis showed that only BRAF V600E mutation was an independent predictor of PFS ( HR=0.23 (95% CI: 0.07-0.80), P=0.021), suggesting that RAIR-DTC patients with BRAF V600E mutation might have better efficacy of apatinib. There was no significant difference in PFS ( χ2=1.34, P=0.247) and OS ( χ2=0.19, P=0.664) between TERT promoter mutation group and wild-type group. Conclusion:RAIR-DTC patients with BRAF V600E mutation have longer PFS and DOR after apatinib treatment than those with BRAF V600E wild-type, suggesting that BRAF V600E may be a potential biomarker to guide tyrosine kinase inhibitor (TKI) therapy and help to refine TKI treatment indications.

19.
Chinese Journal of Hepatobiliary Surgery ; (12): 615-621, 2023.
Article in Chinese | WPRIM | ID: wpr-993384

ABSTRACT

Objective:To observe the influence of NOD-like receptor thermal protein domain associated protein 6 (NLRP6) on hepatic ischemia-reperfusion injury (IRI), and elucidate the related mechanism.Methods:Thirty C57BL/6 mice with body weight of (18.80±1.99) g, were divided randomly into 5 groups, with 6 mice in each group: the mice that experienced only exploratory laparotomy were Sham group; that only underwent an operation to establish a hepatic IRI model were IRI group; that were treated with tail intravenous injection of clodronate (Clo) liposomes before the establishment of hepatic IRI model were Clo group; that received tail intravenous injection of clodronate liposomes and transfusion of bone marrow derived macrophages (BMDM) before the operation were Clo+ BMDM group; that received preoperative tail intravenous injection of clodronate liposomes and transfusion of BMDM with NLRP6 knockdown were Clo+ NLRP6-knockdown group. Real time quantitative polymerase chain reaction analysis (RT-PCR) and Western blot were performed to analyze the expressions of pyroptosis related proteins and factors. Simulate a hypoxia/reoxygenation (H/R) model in vitro, and set up experimental groups: lipopolysaccharide (LPS) + adenosine triphosphate (ATP), LPS+ ATP+ NLRP6-knockdown, H/R, and H/R+ NLRP6-knockdown. The changes of expressions of pyroptosis related proteins and factors were detected by RT-PCR and Western blot. Expression of NF-κB in vivo and in vitro was measured.Results:Compared with those in Sham group, protein expressions of NLRP6, NLRP3, Caspase-1, gasdermin D (GSDMD), IL-1β and IL-18 were remarkably increased in IRI group, but the levels of these proteins were dramatically decreased in Clo group with the exhaustion of macrophages in comparison with in IRI group, which were significantly different statistically (all P<0.05). The levels of these proteins were enhanced again in Clo+ BMDM group with the reconstruction of macrophages in contrast to those in Clo group, while the enhancements were more obvious in Clo+ NLRP6-knockdown group comparing to those in Clo+ BMDM group, with significant differences (all P<0.05). In vitro, pyroptosis rate for LPS+ ATP group was (16.39±1.06)%, which was lower than (27.34±2.79)% for LPS+ ATP+ NLRP6-knockdown group, with a statistical significance ( P<0.05). Meanwhile, pyroptosis rate for H/R group was (20.59±5.66)%, also much more reduced than (37.76±2.00)% for H/R+ NLRP6-knockdown group ( P<0.05). Expressions of NLRP3, Caspase-1, GSDMD, IL-1β, IL-18 and NF-κB p65 in LPS+ ATP+ NLRP6-knockdown group were more elevated than in LPS+ ATP group, and these indices were also more enhanced in H/R+ NLRP6-knockdown group than which in H/R group. Compared to the Sham group, expression of NF-κB p65 significantly increased in IRI group, which was reversed in Clo group, but enhanced again in Clo+ BMDM group and reached a peak in Clo+ NLRP6-knockdown group. Conclusions:Macrophage plays a critical role in immune response to hepatic IRI, wherein NLRP6 functions specifically. NLRP6 acts to suppress inflammation during hepatic IRI through regulating macrophage pyroptosis via inhibiting NF-κB.

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Chinese Journal of Hepatobiliary Surgery ; (12): 278-284, 2023.
Article in Chinese | WPRIM | ID: wpr-993323

ABSTRACT

Objective:To investigate the therapeutic effect and potential molecular mechanisms of cyclin-dependent kinase inhibitor-73 (CDKI-73), the Rab11 inhibitor, on liver fibrosis.Methods:Human LX2 cells were divided into four groups: negative control group, transforming growth factor-β (TGF-β) group, CDKI-73 group and TGF-β+ CDKI-73 group. Fifteen 5-week-old female C57 mice with body weight of (18.04±0.62) g were divided into 3 groups with 5 mice in each group: control group (intraperitoneal injection of olive oil + vehicle gavage), carbon tetrachloride (CCl 4) group (intraperitoneal injection of CCl 4 + vehicle gavage) and CCl 4+ CDKI-73 group (intraperitoneal injection of CCl 4+ CDKI-73 gavage). Another 15 5-week-old female C57 mice with body weight of (18.06±0.34) g were divided into 3 groups with 5 mice in each group: sham operation group (Sham), bile duct ligation (BDL) group + vehicle group (BDL+ vehicle gavage) and bile duct ligation+ CDKI-73 group (BDL+ CDKI-73 gavage). The expression of α-smooth muscle actin (α-SMA) and fibronectin(FN)in LX2 cells were analyzed by Western blot. Masson and Sirius red were used to examine the liver fibrosis after CDKI-73 treatment in vivo. Immunohistochemistry (IHC) was utilized to examine the expression of α-SMA in mice liver. Results:Collagen content assessed by Sirius red and Masson staining and α-SMA expression evaluated by IHC were all increased in CCl 4 group compared with control group ( q=38.47, 24.99, 36.79). Moreover, the collagen content and α-SMA expression in CCl 4 + CDKI-73 treatment group were obviously decreased compared with CCl 4 group ( q=24.72, 14.87, 27.50), and the differences were statistically significant (all P<0.001). Compared with Sham group, collagen content and α-SMA expression in bile duct ligation group were increased ( q=28.23, 41.01, 44.16). Furthermore, in BDL group, after treatment with CDKI-73, the collagen content and α-SMA expression were notably decreased ( q=22.88, 34.31 and 33.97, all P<0.001). Consistent with in vivo results, the relative expression levels of α-SMA and FN protein in TGF-β group were higher than those in TGF-β+ CDKI-73 group (α-SMA: 3.71±0.34 vs. 1.28±0.31; FN: 3.21±0.39 vs. 0.83±0.06, all P<0.001). The mRNA relative expression levels of α-SMA and FN in TGF-β group were higher than those in TGF-β+ CDKI-73 group, and the differences were statistically significant ( P<0.001). However, the relative expression of TGF-β receptor Ⅱ protein in CDKI-73 group was higher than those in negative control group (4.68±0.63 vs. 1.00±0.22, P=0.004). The relative expression level of phosphorylated SMAD2 in TGF-β+ CDKI-73 group was lower than those in TGF-β group (1.67±0.24 vs. 3.99±0.44, P<0.001). Transwell assay showed that 0.5 μmol/L CDKI-73 could effectively inhibit the migration of LX2 cells, and the inhibitory ability became stronger with the increase of CDKI-73 concentration. Conclusion:CDKI-73 can inhibit the activation of hepatic stellate cells and liver fibrosis by inhibiting Rab11-dependent TGF-β signaling pathway both in vivo and in vitro.

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