1.Role of Wnt signaling Pathway in Diabetic Osteoporosis and Traditional Chinese Medicine Intervention: A Review
Yaqi ZHANG ; Weiguo WANG ; Qidong ZHANG ; Huizhong BAI ; Lingling QIN ; Feng GAO
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(9):283-292
Diabetic osteoporosis (DOP) is a kind of bone complication caused by diabetes, which is characterized by the decrease of bone mineral density, the change of bone microstructure and the increase of bone fragility. The process of DOP is closely related to high glucose, insulin resistance, oxidative stress and other mechanisms. The Wnt/β-catenin signaling pathway plays an important role in mediating insulin resistance and bone metabolic balance in diabetes. Regulation of Wnt signal transduction promotes the expression of glycogen synthase kinase-3β(GSK-3β)phosphorylation and improves glucose and lipid metabolism. The Wnt/β-catenin signaling pathway is also an important way regulating osteocyte-driven bone remodeling, which not only plays an important regulatory role in the balance between osteoblasts and osteoclasts and improve bone metabolic homeostasis, but also promotes the expression of osteopontin, osteocalcin and type Ⅰ collagen, and improves bone proliferation and osteogenic differentiation by regulating the Wnt pathway. In recent years, the research of traditional Chinese medicine (TCM) in the prevention and treatment of DOP has gradually increased, and the exploration of TCM to interfere with the Wnt pathway to improve DOP has made some progress. This paper collects and summarizes the studies on the Wnt signaling pathway in glucose metabolism, bone metabolism and DOP worldwide in the past decade, as well as the related literature on the intervention of DOP by TCM compounds (classical and other compounds), single Chinese medicine and TCM monomers based on the Wnt pathway, in order to provide a reference and direction for the development of new drugs for clinical prevention and treatment of DOP.
2.Impacts of participation in surgical clinical trial on safety and survival outcomes in patients with right-sided colon cancer
Huaqing ZHANG ; Guoqiang WANG ; Bin WU ; Guole LIN ; Huizhong QIU ; Beizhan NIU ; Junyang LU ; Lai XU ; Xiyu SUN ; Guannan ZHANG ; Yi XIAO
Chinese Journal of Gastrointestinal Surgery 2024;27(9):928-937
Objective:To explore the impact on safety and prognosis in patients with right-sided colon cancer participating in surgical clinical research.Methods:This retrospective cohort study utilized data from a randomized controlled trial (RELARC study) conducted by the colorectal surgery group at Peking Union Medical College Hospital in which laparoscopic complete mesocolic excision (CME) was compared with D2 radical resection for the management of right-sided colon cancer. The eligibility criteria were age 18–75 years, biopsy-proven colon adenocarcinoma, tumor located between the cecum and right 1/3 of the transverse colon, enhanced chest, abdomen, and pelvic CT scans suggesting tumor stage T2–T4N0M0 or TanyN+ M0, and having undergone radical surgical treatment from January 2016 to December 2019. Exclusion factors included multiple primary colorectal cancers, preoperative stage T1N0 or enlarged central lymph nodes, tumor involving surrounding organs requiring their resection, definite distant metastasis or otherwise unable to undergo R0 resection, history of any other malignant tumors within previous 5 years, intestinal obstruction, perforation, or gastrointestinal bleeding requiring emergency surgery, and assessed as unsuitable for laparoscopic surgery. Patients who had participated in the RELARC study were included in the RELARC group, whereas those who met the inclusion criteria but refused to participate in the RELAEC study were included in the control group. The main indicators studied were the patient's baseline data, surgery and perioperative conditions, pathological characteristics, adjuvant treatment, and postoperative follow-up (including average frequency of follow-up within the first 3 years) and survival (including 3-year disease-free survival rate (DFS) and 3-year overall survival rate (OS). Differences in these indicators between the RELARC and control groups were compared.Results:The study cohort comprised 290 patients, 173 in the RELARC group (RELARC-CME group, 82; RELARC-D2 group, 91) and 117 in the control group (CME control group, 72; D2 control group, 45). There was a significantly higher proportion of overweight patients (BMI ≥24 kg/m 2) in the RELARC-CME than in the CME control group (67.1% [55/82] vs. 33.3% [24/72], χ 2=17.469, P<0.001). There were no other statistically significant differences in baseline characteristics (all P>0.05). No significant disparities were found between the CME and D2 groups in terms of operation duration, intraoperative blood loss, rate of conversion to open surgery, combined organ resection, intraoperative blood transfusion, or intraoperative complications (all P>0.05). There was a trend toward Clavien–Dindo grade II or higher postoperative complications in the RELARC-CME group (24.4% [20/82]) than in the CME control group (18.1% [13/72]); however, this difference was not statistically significant (χ 2=0.914, P=0.339). Similarly, the difference in this rate did not differ significantly between the RELARC-D2 group (25.3% [23/91]) and D2 control group (24.4% [11/45], χ 2=0.011, P=0.916). The median duration of postoperative follow-up was significantly shorter in the RELARC groups than in the corresponding control groups. Specifically, the median duration of follow-up was 4.5 (4.5, 4.5) months in the RELARC-CME and 7.2 (6.0, 9.0) months in the CME control group ( Z=-10.608, P<0.001). Similarly, the median duration of follow-up was 4.5 (4.5, 4.5) months in the RELARC-D2 group as opposed to 8.3 (6.6, 9.0) months in the D2 control group ( Z=-10.595, P<0.001). The 3-year DFS rate (91.5%) and OS rate (96.3%) tended to be higher in the RELARC-CME group than in the CME control group (84.7% and 90.3%, respectively). The 3-year DFS rate (87.9%) and OS rate (96.7%) tended to be higher in the RELARC-D2 group than in the D2 control group (81.8% and 88.6%, respectively); however, these differences were not statistically significant (all P>0.05). Subgroup analysis according to pathological stage revealed that patients in the RELARC-D2 group with pN0 stage achieved a significantly superior 3-year OS rate than did those in the D2 control group (100% vs. 88.9%, P=0.008). We identified no statistically significant differences in survival rates between the remaining subgroups (all P>0.05). Conclusions:A high-quality surgical clinical trial with close follow-up can achieve perioperative safety and a trend toward improved survival outcomes.
3.Hypolipidemic effect of flavonoids in hyperlipidaemic rats and study of PPARαpathway in blue prickly head flavonoids
Ruining LIU ; Jianbing ZHANG ; Huizhong ZHANG ; Han WANG ; Puguo HAO ; Yu GUO ; Yu WANG ; Hongxia ZHAO
Chinese Journal of Veterinary Science 2024;44(10):2243-2250
Hyperlipidaemic rats were randomly divided into a model group,a total flavonoids from echinops latifolius tausch(TFET)high,medium and low dose group,and a positive control group;meanwhile,healthy rats were selected as a blank control group.The rats in each group were dosed with the corresponding concentrations of TFET,simvastatin and distilled water for 45 consecutive days,and were tested for relevant lipid biochemical indexes,antioxidant indexes and PPARα path-way-related gene expression.The results showed that high-dose TFET could reduce the concentra-tions of TC,TG and LDL-C and increase the concentration of HDL-C very significantly;medium-dose TFET could reduce the concentrations of TC and TG very significantly and reduce the con-centration of LDL-C significantly;and low-dose TFET could reduce the concentrations of TC and LDL-C significantly.High,medium and low doses of TFET can extremely significantly reduce in-crease SOD activity;high and medium doses of TFET can extremely significantly reduce MDA content;high dose of TFET can extremely significantly increase T-AOC activity.The high dose of TFET could extremely significantly increase the expression of PPARα,CYP7A1 and CPT-1 genes in rat liver;the medium dose of TFET could extremely significantly increase the expression of CYP7A1 and CPT-1 genes,and could significantly increase the expression of PPARα gene;the low dose of TFET could extremely significantly increase the expression of CYP7A1 gene,and signifi-cantly increase the CPT-1 gene expression.The results suggest that TFET has antioxidant and lip-id-lowering effects on hyperlipidaemic rats,and its mechanism may be related to the activation of PPARα and its downstream related genes to promote fatty acid β-oxidation.
4.Interaction analysis of mismatch repair protein and adverse clinicopathological features on prognosis of colon cancer
Kexuan LI ; Fuqiang ZHAO ; Qingbin WU ; Junling ZHANG ; Shuangling LUO ; Shidong HU ; Bin WU ; Heli LI ; Guole LIN ; Huizhong QIU ; Junyang LU ; Lai XU ; Zheng WANG ; Xiaohui DU ; Liang KANG ; Xin WANG ; Ziqiang WANG ; Qian LIU ; Yi XIAO
Chinese Journal of Digestive Surgery 2024;23(6):826-835
Objective:To investigate the interactive effect of mismatch repair (MMR) protein status and adverse clinicopathological features on prognosis of stage Ⅰ-Ⅲ colon cancer.Methods:The retrospective cohort study was conducted. The clinicopathological data of 1 650 patients with colon cancer of stage Ⅰ-Ⅲ who were admitted to 7 hospitals in China from January 2016 to December 2017 were collected. There were 963 males and 687 females, aged 62(53,71)years. Patients were classified as 230 cases of MMR deficiency (dMMR) and 1 420 cases of MMR proficiency (pMMR) based on their MMR protein status. Observation indicators: (1) comparison of clinicopathological characteristics between patients of different MMR protein status; (2) analysis of factors affecting the survival outcomes of patients of dMMR; (3) analysis of factors affecting the survival outcomes of patients of pMMR; (4) interaction analysis of MMR and adverse clinicopathological features on survival outcomes. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the independent t test. Measurement data with skewed distribution were represented as M( Q1, Q3), and comparison between groups was conducted using the Mann-Whitney U test. Count data were described as absolute numbers, and comparison between groups was conducted using the chi-square test or Fisher exact probability. Comparison of ordinal data was conducted using the Mann-Whitney U test. The random forest interpolation method was used for missing values in data interpolation. Univariate analysis was conducted using the COX proportional risk regression model, and multivariate analysis was conducted using the COX stepwise regression with forward method. The coefficient of multiplication interaction effect was obtained using the interaction term coefficient of COX proportional risk regression model. Evaluation of additive interaction effects was conducted using the relative excess risk due to interaction ( RERI). Results:(1) Comparison of clinicopathological characteristics between patients of different MMR protein status. There were significant differences in age, T staging, the number of lymph node harvest, the number of lymph node harvest <12, high grade tumor between patients of dMMR and pMMR ( P<0.05). (2) Analysis of factors affecting the survival outcomes of patients of dMMR. Results of multivariate analysis showed that T staging, N staging, the number of lymph node harvest <12 were independent factors affecting the disease-free survival (DFS) of colon cancer patients of dMMR ( hazard ratio=3.548, 2.589, 6.702, 95% confidence interval as 1.460-8.620, 1.064-6.301, 1.886-23.813, P<0.05). Age and N staging were independent factors affecting the overall survival (OS) of colon cancer patients of dMMR ( hazard ratio=1.073, 10.684, 95% confidence interval as 1.021-1.126, 2.311-49.404, P<0.05). (3) Analysis of factors affecting the survival outcomes of patients of pMMR. Results of multivariate analysis showed that age, T staging, N staging, vascular tumor thrombus were independent factors affecting the DFS of colon cancer patients of pMMR ( hazard ratio=1.018, 2.214, 2.598, 1.549, 95% confidence interval as 1.006-1.030, 1.618-3.030, 1.921-3.513, 1.118-2.147, P<0.05). Age, T staging, N staging, high grade tumor were independent factors affecting the OS of colon cancer patients of pMMR ( hazard ratio=1.036, 2.080, 2.591, 1.615, 95% confidence interval as 1.020-1.052, 1.407-3.075, 1.791-3.748, 1.114-2.341, P<0.05). (4) Interaction analysis of MMR and adverse clinicopathological features on survival outcomes. Results of interaction analysis showed that the multiplication interaction effect between the number of lymph node harvest <12 and MMR protein status was significant on DFS of colon cancer patients ( hazard ratio=3.923, 95% confidence interval as 1.057-14.555, P<0.05). The additive interaction effects between age and MMR protein status, between high grade tumor and MMR protein status were significant on OS of colon cancer patients ( RERI=-0.033, -1.304, 95% confidence interval as -0.049 to -0.018, -2.462 to -0.146). Conclusions:There is an interaction between the MMR protein status and the adverse clinicopathological features (the number of lymph node harvest <12, high grade tumor) on prognosis of colon cancer patients of stage Ⅰ-Ⅲ. In patients of dMMR, the number of lymph node harvest <12 has a stronger predictive effect on poor prognosis. In patients of pMMR, the high grade tumor has a stronger predictive effect on poor prognosis.
5.Mechanism of Polyphyllin Ⅱ in Induction of Ferroptosis in Hepatocellular Carcinoma HepG2 Cells
Huizhong ZHANG ; Jian NI ; Hulinyue PENG ; Yibo ZHANG ; Xiaohan XU ; Shiman LI ; Yidan RUAN ; Yongqiang ZHANG ; Pingzhi ZHANG ; Aina YAO ; Ying WANG ; Xiaoxu DONG
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(17):105-112
ObjectiveTo investigate the induction of ferroptosis by polyphyllin Ⅱ (PPⅡ) in hepatocellular carcinoma HepG2 cells and its underlying mechanism. MethodThe effect of PPⅡ (0, 1.5, 3.0, 4.5, 6.0, 9.0, 18.0 mg·L-1) on the in vitro proliferation of HepG2 cells was assessed using the methyl thiazolyl tetrazolium (MTT) assay. Colony formation ability of HepG2 cells was evaluated through a colony formation assay. Cell migration ability was assessed via a scratch assay. Lactate dehydrogenase (LDH) content in HepG2 cells was measured using a kit. Reactive oxygen species (ROS) levels in HepG2 cells were observed using a fluorescence inverted microscope. Malondialdehyde (MDA), glutathione (GSH), and free Fe2+ content in HepG2 cells were detected using respective kits. The mitochondrial ultrastructure in HepG2 cells was observed by transmission electron microscopy. The expression of ferroptosis-related proteins p53, solute carrier family 7 member 11 (SLC7A11), glutathione peroxidase 4 (GPX4), long-chain acyl-CoA synthetase 4 (ACSL4), and transferrin receptor 1 (TFR1) in HepG2 cells was detected using Western blot. ResultCompared with the control group, the PPⅡ treatment groups showed significantly decreased survival rate of HepG2 cells in a dose-dependent manner (P<0.01), significantly reduced number of cell colonies (P<0.01), significantly shortened scratch healing distance, inverse correlation of the migration distance with drug concentration (P<0.01), significantly increased LDH leakage in cells (P<0.01), significantly enhanced relative fluorescence intensity of intracellular ROS, and significantly increased accumulation of lipid peroxide MDA (P<0.01), decreased intracellular GSH content with increasing drug concentration (P<0.01), and significantly enhanced fluorescence intensity of FeRhoNox-1 in cells (P<0.01). Moreover, cells exhibited vacuolation, and mitochondria showed significant shrinkage with reduced or even disappeared cristae. Compared with the results in the control group, the expression of p53, ACSL4, and TFR1 proteins significantly increased, while the expression of SLC7A11 and GPX4 proteins significantly decreased in the PPⅡ treatment groups (P<0.05). ConclusionIn summary, PPⅡ induces ferroptosis in HepG2 cells by regulating the p53/SLC7A11/GPX4 signaling axis, promoting ACSL4 expression and Fe3+ uptake, leading to an imbalance in the antioxidant system.
6.Impacts of participation in surgical clinical trial on safety and survival outcomes in patients with right-sided colon cancer
Huaqing ZHANG ; Guoqiang WANG ; Bin WU ; Guole LIN ; Huizhong QIU ; Beizhan NIU ; Junyang LU ; Lai XU ; Xiyu SUN ; Guannan ZHANG ; Yi XIAO
Chinese Journal of Gastrointestinal Surgery 2024;27(9):928-937
Objective:To explore the impact on safety and prognosis in patients with right-sided colon cancer participating in surgical clinical research.Methods:This retrospective cohort study utilized data from a randomized controlled trial (RELARC study) conducted by the colorectal surgery group at Peking Union Medical College Hospital in which laparoscopic complete mesocolic excision (CME) was compared with D2 radical resection for the management of right-sided colon cancer. The eligibility criteria were age 18–75 years, biopsy-proven colon adenocarcinoma, tumor located between the cecum and right 1/3 of the transverse colon, enhanced chest, abdomen, and pelvic CT scans suggesting tumor stage T2–T4N0M0 or TanyN+ M0, and having undergone radical surgical treatment from January 2016 to December 2019. Exclusion factors included multiple primary colorectal cancers, preoperative stage T1N0 or enlarged central lymph nodes, tumor involving surrounding organs requiring their resection, definite distant metastasis or otherwise unable to undergo R0 resection, history of any other malignant tumors within previous 5 years, intestinal obstruction, perforation, or gastrointestinal bleeding requiring emergency surgery, and assessed as unsuitable for laparoscopic surgery. Patients who had participated in the RELARC study were included in the RELARC group, whereas those who met the inclusion criteria but refused to participate in the RELAEC study were included in the control group. The main indicators studied were the patient's baseline data, surgery and perioperative conditions, pathological characteristics, adjuvant treatment, and postoperative follow-up (including average frequency of follow-up within the first 3 years) and survival (including 3-year disease-free survival rate (DFS) and 3-year overall survival rate (OS). Differences in these indicators between the RELARC and control groups were compared.Results:The study cohort comprised 290 patients, 173 in the RELARC group (RELARC-CME group, 82; RELARC-D2 group, 91) and 117 in the control group (CME control group, 72; D2 control group, 45). There was a significantly higher proportion of overweight patients (BMI ≥24 kg/m 2) in the RELARC-CME than in the CME control group (67.1% [55/82] vs. 33.3% [24/72], χ 2=17.469, P<0.001). There were no other statistically significant differences in baseline characteristics (all P>0.05). No significant disparities were found between the CME and D2 groups in terms of operation duration, intraoperative blood loss, rate of conversion to open surgery, combined organ resection, intraoperative blood transfusion, or intraoperative complications (all P>0.05). There was a trend toward Clavien–Dindo grade II or higher postoperative complications in the RELARC-CME group (24.4% [20/82]) than in the CME control group (18.1% [13/72]); however, this difference was not statistically significant (χ 2=0.914, P=0.339). Similarly, the difference in this rate did not differ significantly between the RELARC-D2 group (25.3% [23/91]) and D2 control group (24.4% [11/45], χ 2=0.011, P=0.916). The median duration of postoperative follow-up was significantly shorter in the RELARC groups than in the corresponding control groups. Specifically, the median duration of follow-up was 4.5 (4.5, 4.5) months in the RELARC-CME and 7.2 (6.0, 9.0) months in the CME control group ( Z=-10.608, P<0.001). Similarly, the median duration of follow-up was 4.5 (4.5, 4.5) months in the RELARC-D2 group as opposed to 8.3 (6.6, 9.0) months in the D2 control group ( Z=-10.595, P<0.001). The 3-year DFS rate (91.5%) and OS rate (96.3%) tended to be higher in the RELARC-CME group than in the CME control group (84.7% and 90.3%, respectively). The 3-year DFS rate (87.9%) and OS rate (96.7%) tended to be higher in the RELARC-D2 group than in the D2 control group (81.8% and 88.6%, respectively); however, these differences were not statistically significant (all P>0.05). Subgroup analysis according to pathological stage revealed that patients in the RELARC-D2 group with pN0 stage achieved a significantly superior 3-year OS rate than did those in the D2 control group (100% vs. 88.9%, P=0.008). We identified no statistically significant differences in survival rates between the remaining subgroups (all P>0.05). Conclusions:A high-quality surgical clinical trial with close follow-up can achieve perioperative safety and a trend toward improved survival outcomes.
7.Length of stay and inpatient charges of total knee arthroplasty in China: analysis of a national database.
Huizhong LONG ; Chao ZENG ; Ying SHI ; Haibo WANG ; Dongxing XIE ; Guanghua LEI
Chinese Medical Journal 2023;136(17):2050-2057
BACKGROUND:
There are limited data on the resource utilization of total knee arthroplasty (TKA) in China. This study aimed to examine the length of stay (LOS) and inpatient charges of TKA in China, and to investigate their determinants.
METHODS:
We included patients undergoing primary TKA in the Hospital Quality Monitoring System in China between 2013 and 2019. LOS and inpatient charges were obtained, and their associated factors were further assessed using multivariable linear regression.
RESULTS:
A total of 184,363 TKAs were included. The LOS decreased from 10.8 days in 2013 to 9.3 days in 2019. The admission-to-surgery interval decreased from 4.6 to 4.2 days. The mean inpatient charges were 61,208.3 Chinese Yuan. Inpatient charges reached a peak in 2016, after which a gradual decrease was observed. Implant and material charges accounted for a dominating percentage, but they exhibited a downward trend, whereas labor-related charges gradually increased. Single marital status, non-osteoarthritis indication, and comorbidity were associated with longer LOS and higher inpatient charges. Female sex and younger age were associated with higher inpatient charges. There were apparent varieties of LOS and inpatient charges among provincial or non-provincial hospitals, hospitals with various TKA volume, or in different geographic regions.
CONCLUSIONS
The LOS following TKA in China appeared to be long, but it was shortened during the time period of 2013 to 2019. The inpatient charges dominated by implant and material charges exhibited a downward trend. However, there were apparent sociodemographic and hospital-related discrepancies of resource utilization. The observed statistics can lead to more efficient resource utilization of TKA in China.
Length of Stay
;
Fees and Charges
;
Arthroplasty, Replacement, Knee/economics*
;
China
;
Humans
;
Databases, Factual
;
Male
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Female
;
Middle Aged
;
Aged
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Aged, 80 and over
;
Inpatients
8.Explore the Intervention Mechanism of Guizhi Fuling Pills on Breast Cancer Based on Multi-data Platform
Xuemei WANG ; Huizhong BAO ; Tianyue MA ; Huiying LUO
Chinese Journal of Modern Applied Pharmacy 2023;40(24):3389-3398
Abstract
OBJECTIVE To explore the intervention mechanism of Guizhi Fuling pills on breast cancer based on multi-data platform and bioinformation technology, and to verify the analysis results by cell test. METHODS The data set related to breast cancer was downloaded from GEO database to analyze the differential genes of breast cancer. The main active components and target genes of Guizhi Fuling pills were screened from TCMSP database. The key target genes of Guizhi Fuling pills in the treatment of breast cancer were mapped by the two groups of target genes. TCGA database was used to analyze the expression of key target genes in breast cancer. Through TIMER, CPTAC Data Portal, and Kaplan-Meier plotter, TISIDB, SangerBox and other data platforms, the relationships of the key genes expression and immune micro-environment, immune infiltration level, genomic heterogeneity, immune subtypes, molecular subtype, and poor prognosis were analyzed in breast cancer. KEGG pathway enrichment of key genes was performed searching for possible signaling pathways by Metascape analysis platform. Finally, CCK-8 assay, cell scratch assay, Transwell chamber assay and Western blotting technique were used to verify the results in vitro. RESULTS There were 42 active components and 185 targets in Guizhi Fuling pills, and 14 key targets related to the treatment of breast cancer were mapped with GEO database. Six key target genes for the treatment of breast cancer were obtained by comparison with breast cancer differential genes in TCGA. The expression of these 6 key genes was strongly correlated with the levels of 6 immune cells, 3 immune microenvironment scores, immune subtypes and molecular subtypes in breast cancer(P<0.05), also showed consistency in the correlation of genomic heterogeneity, and was closely associated with poor prognosis(P<0.05). KEGG enrichment analysis showed that these 6 genes were mainly enriched in PI3K/Akt signaling pathways. Cell test showed that Guizhi Fuling pills could significantly inhibit the proliferation, migration and invasion of HCC1937 cells, and also reduce the relative expression of p-Akt/Akt and p-PI3K/PI3K proteins in HCC1937 cells in a dose-dependent manner. CONCLUSION Guizhi Fuling pills may interfere with breast cancer by blocking PI3K/Akt signaling pathway and regulating the tumor immune microenvironment.
9.In-hospital mortality and related risk factors after knee replacement in China: based on national hospital quality monitoring system data
Huizhong LONG ; Chao ZENG ; Hu CHEN ; Yilin XIONG ; Qiao JIANG ; Dongxing XIE ; Yilun WANG ; Jie WEI ; Ying SHI ; Haibo WANG ; Yongcheng HU ; Guanghua LEI
Chinese Journal of Orthopaedics 2022;42(11):730-738
Objective:To estimate in-hospital mortality after knee replacement (KR) and to assess its trend and risk factors in China.Methods:We included patients undergoing KR in the Hospital Quality Monitoring System in China (2013-2019) to estimate in-hospital mortality after KR and assessed relation of patient's and hospital's characteristics (year of surgery, age, gender, marital status, primary indication, Charlson comorbidity index, geographic location, hospital type, hospital volume of KR, and surgery type) to in-hospital mortality using multivariable Poisson regression.Results:The annual amount of KR has increased from 20 307 in 2013 to 35 757 in 2019, and has maintained an upward trend for 7 years. The mean age of patients having KR increased from 64.9 years in 2013 to 66.6 years in 2019. Of the total 218 923 KRs, 63 deaths (0.29‰) occurred within 30 days before discharging. Older age was associated with higher in-hospital mortality ( P for trend <0.001). Male gender had higher incidence of in-hospital mortality compared with female [relative risk (RR), 2.5; 95% CI: 1.5, 4.1]. Single marital status was associated with higher, albeit non-statistically significant, in-hospital mortality than married patients (RR, 2.1; 95% CI: 0.9, 4.6). Higher Charlson comorbidity index was associated with increased risk of in-hospital mortality ( P for trend <0.001). Risk of in-hospital mortality decreased with more hospital-year knee replacement surgeries ( P for trend <0.001). In-hospital mortality varied by geographic regions, with the lowest mortality in East region (0.16‰), followed by South-West (0.31‰), South-Central (0.31‰), North region (0.33‰), North-West (0.54‰) and North-East (0.59‰). Conclusion:In-hospital mortality after KR in China was relatively low. Older age, male gender, higher Charlson comorbidity index and lower hospital-year knee replacement surgeries were risk factors for in-hospital mortality. The mortality varied greatly according to the geographic location of hospital.
10.Diagnostic value of serum TIM-3 in patients with liver cancer
Ting HE ; Xi WANG ; Huizhong ZHANG ; Xinyang LIU ; Huiping WANG ; Ke DONG
Journal of International Oncology 2022;49(9):537-542
Objective:To analyze the changes of T cell immunoglobulin- and mucin-domain-containing molecule-3 (TIM-3) in serum of patients with liver cancer and its diagnostic value.Methods:From March 2021 to May 2021, 37 patients with viral hepatitis type B (hepatitis B group) , 44 patients with liver cirrhosis (liver cirrhosis group) and 27 patients with liver cancer (liver cancer group) were selected in the Second Affiliated Hospital of Air Force Medical University, and 35 healthy subjects who underwent physical examination during the same period were selected as the healthy control group. The serum alpha fetoprotein (AFP) , liver function indexes and TIM-3 levels were detected, and the differences among groups were analyzed. The correlations between TIM-3 and AFP and liver function indexes were analyzed by Spearman correlation. Receiver operating characteristic (ROC) curve was used to analyze the diagnostic value of TIM-3 in liver cancer.Results:There was a statistically significant difference in AFP among the hepatitis B group, liver cirrhosis group and liver cancer group ( χ2=11.75, P=0.003) . There were statistically significant differences in total bilirubin ( χ2=22.85, P<0.001) , direct bilirubin ( χ2=25.90, P<0.001) , indirect bilirubin ( χ2=19.92, P<0.001) , alanine aminotransferase ( χ2=36.64, P<0.001) , aspertate aminotransferase ( χ2=26.26, P<0.001) , aspertate aminotransferase/alanine aminotransferase ( χ2=34.67, P<0.001) and total bile acid ( χ2=13.10, P<0.001) among the hepatitis B group, liver cirrhosis group and liver cancer group. The serum levels of TIM-3 in the healthy control group, hepatitis B group, liver cirrhosis group and liver cancer group were 11.1 (4.2, 14.4) ng/ml, 12.7 (4.3, 23.9) ng/ml, 11.4 (3.4, 17.0) ng/ml and 15.7 (10.5, 21.2) ng/ml, with a statistically significant difference ( χ2=11.85, P=0.008) . There were statistically significant differences between the liver cancer group and healthy control group and liver cirrhosis group (both P<0.05) . Spearman correlation analysis showed that TIM-3 had no correlation with AFP in the four groups ( r=0.05, P=0.791; r=0.18, P=0.497; r=0.03, P=0.883; r=0.24, P=0.396) . There were correlations between serum TIM-3 and total protein in the healthy control group ( r=0.36, P=0.036) , serum TIM-3 and globulin in the hepatitis B group ( r=0.35, P=0.034) , and serum TIM-3 and total bile acid in the liver cancer group ( r=0.46, P=0.017) . ROC curve analysis showed that the sensitivity of serum TIM-3 for the diagnosis of liver cancer was 48.10%, and the specificity was 91.43%, when taking healthy subjects as the control group. The sensitivity of serum TIM-3 for the diagnosis of liver cancer was 96.30%, and the specificity was 41.77%, when taking healthy subjects and liver cirrhosis patients as the control group. The sensitivity of serum TIM-3 for the diagnosis of liver cancer was 96.30%, and the specificity was 40.52%, when taking healthy subjects, hepatitis B patients and liver cirrhosis patients as the control group. Conclusion:The serum level of TIM-3 in patients with liver cancer is significantly increased, which has certain diagnostic value for liver cancer, and can be used as a diagnostic marker and potential therapeutic target for liver cancer patients.


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