1.A qualitative study on the awareness and management strategy improvement of childhood hypertension
ZHOU Jiali, ZHANG Chenhao, SUN Weidi, HOU Leying, LUO Zeyu, ZHU Bing, ZHANG Ronghua, SONG Peige
Chinese Journal of School Health 2025;46(4):524-527
Objective:
To summarize strategies for improving childhood hypertension, so as to provide evidencebased recommendations for poliymaking and practice childhood hypertension management in China.
Methods:
From March to April 2024, child health stakeholders from five districts in Hangzhou were selected using a combination of stratified and convenience sampling methods. Data were analyzed using a groundedtheory approach. During the indepth interview phase, six policymakers were interviewed. Focus group discussions were conducted with school administrators, healthcare providers, and parents, comprising a total of 62 participants.
Results:
Through threelevel coding, 116 initial categories were identified(e.g., "trend of younger age" "difficulty in behavior change"), 35 main categories (e.g., "higher incidence compared to the past" "caused by comprehensive influencing factors"), and 12 core categories (e.g., "epidemic status" "influencing factors"). Finally, the cognitive status, problem analysis, and management strategies of children hypertension were constructed.
Conclusion
Effective prevention and control of childhood hypertension requires coordinated efforts among governments, schools, families, and society to establish a comprehensive management system, with dynamic monitoring and evaluation to optimize policy implementation.
2.Multi-dimensional influencing factors and strategies for prevention and control of childhood hypertension
ZHOU Jiali, WU Jing, LIU Runqi, TANG Ke, ZHU Bing, ZHANG Ronghua, SONG Peige
Chinese Journal of School Health 2025;46(6):765-769
Abstract
Childhood hypertension is becoming a substantial public health challenge with profound implications for children s quality of life and long term health. The study analyzes the global prevalence of childhood hypertension and the relationship between macroecological factors, meso environmental factors, and micro individual factors based on the perspective of life course and childhood hypertension. And it further summarizes existing prevention and control strategies: systematic prevention and control based on policy and social support, health promotion based on behavioral science theory, and dynamic monitoring and management based on individualized prevention and control, to provide a reference for promoting the advancement of childhood hypertension prevention and control strategies.
3.Lichong Xiaozheng Granules enhances cisplatin sensitivity of ovarian cancer xenografts in rats by regulating adenine nucleotide translocator 3-mediated mitochondrial apoptosis.
Yiliu CHEN ; Min MA ; Ran SU ; Yinbin ZHU ; Qing FENG ; Jiali LUO ; Weifeng FENG ; Xianxin YAN
Journal of Southern Medical University 2025;45(11):2309-2319
OBJECTIVES:
To investigate the molecular mechanism by which Lichong Xiaozheng Granules (LCXZ) sensitize ovarian cancer to cisplatin (DDP) treatment.
METHODS:
LC-MS analysis was used to identify the blood components of LCXZ after its administration in mice via gavage. In a BALB/c mouse model bearing subcutaneous ovarian cancer xenografts, the effects of daily gavage of distilled water (control group), intraperitoneal injection of DDP (5 mg/kg) once a week, or both DDP injection and daily LCXZK gavage (15 g/kg) on tumor growth were evaluated. Histopathological changes in the xenografts and kidneys were assessed with HE staining. RNA-seq was performed to identify the differentially expressed genes followed by KEGG pathway analysis. The changes in mitochondrial ultrastructure and expressions of mitochondrial apoptosis-related were examined with transmission electron microscopy and Western blotting.
RESULTS:
A total of 218 blood-borne components of LCXZ were detected by LC-MS. In the tumor-bearing mice, treatments with DDP and DDP combined with LCXZ redcued the tumor volume by 60.3% and 72.6% compared with that in the control group, respectively. Transcriptomic analysis revealed significantly upregulated ANT3 expression in both the two treatment groups. Molecular docking indicated that the main active components of LCXZ were capable of binding to adenine nucleotide translocator 3 (ANT3) with binding energies below -6 kcal/mol. Transmission electron microscopy showed obvious mitochondrial swelling and outer-membrane damage in the tumor cells in DDP-treated mice, and these changes were more pronounced in the combined treatment group. The expression levels of BAX, ANT3, cleaved caspase-3 and cleaved caspase-9 were increased, whereas BCL-2 expression was decreased significantly in the tumor cells in both the DDP and DDP+LCXZ groups.
CONCLUSIONS
LCXZ enhances the therapeutic efficacy of cisplatin against ovarian cancer xenografts in mice by promoting mitochondrial dysfunction and activating apoptotic signaling pathways via upregulating ANT3.
Animals
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Female
;
Cisplatin/pharmacology*
;
Ovarian Neoplasms/metabolism*
;
Apoptosis/drug effects*
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Mitochondria/metabolism*
;
Drugs, Chinese Herbal/pharmacology*
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Mice, Inbred BALB C
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Mice
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Rats
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Xenograft Model Antitumor Assays
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Humans
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Cell Line, Tumor
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Antineoplastic Agents/pharmacology*
4.Potassium dehydroandrographolide succinate regulates the MyD88/CDH13 signaling pathway to enhance vascular injury-induced pathological vascular remodeling.
Qiru GUO ; Jiali LI ; Zheng WANG ; Xiao WU ; Zhong JIN ; Song ZHU ; Hongfei LI ; Delai ZHANG ; Wangming HU ; Huan XU ; Lan YANG ; Liangqin SHI ; Yong WANG
Chinese Journal of Natural Medicines (English Ed.) 2024;22(1):62-74
Pathological vascular remodeling is a hallmark of various vascular diseases. Previous research has established the significance of andrographolide in maintaining gastric vascular homeostasis and its pivotal role in modulating endothelial barrier dysfunction, which leads to pathological vascular remodeling. Potassium dehydroandrographolide succinate (PDA), a derivative of andrographolide, has been clinically utilized in the treatment of inflammatory diseases precipitated by viral infections. This study investigates the potential of PDA in regulating pathological vascular remodeling. The effect of PDA on vascular remodeling was assessed through the complete ligation of the carotid artery in C57BL/6 mice. Experimental approaches, including rat aortic primary smooth muscle cell culture, flow cytometry, bromodeoxyuridine (BrdU) incorporation assay, Boyden chamber cell migration assay, spheroid sprouting assay, and Matrigel-based tube formation assay, were employed to evaluate the influence of PDA on the proliferation and motility of smooth muscle cells (SMCs). Molecular docking simulations and co-immunoprecipitation assays were conducted to examine protein interactions. The results revealed that PDA exacerbates vascular injury-induced pathological remodeling, as evidenced by enhanced neointima formation. PDA treatment significantly increased the proliferation and migration of SMCs. Further mechanistic studies disclosed that PDA upregulated myeloid differentiation factor 88 (MyD88) expression in SMCs and interacted with T-cadherin (CDH13). This interaction augmented proliferation, migration, and extracellular matrix deposition, culminating in pathological vascular remodeling. Our findings underscore the critical role of PDA in the regulation of pathological vascular remodeling, mediated through the MyD88/CDH13 signaling pathway.
Mice
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Rats
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Animals
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Myeloid Differentiation Factor 88/metabolism*
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Vascular Remodeling
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Cell Proliferation
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Vascular System Injuries/pathology*
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Carotid Artery Injuries/pathology*
;
Molecular Docking Simulation
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Muscle, Smooth, Vascular
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Cell Movement
;
Mice, Inbred C57BL
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Signal Transduction
;
Succinates/pharmacology*
;
Potassium/pharmacology*
;
Cells, Cultured
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Diterpenes
;
Cadherins
5.The Effects of Wenfei Huaxian Decoction (温肺化纤汤) on Pulmonary Fibrosis and Endoplasmic Reticulum Stress in Systemic Sclerosis-Associated Interstitial Lung Disease Model Mice
Mingliang QIU ; Jiali XIONG ; Chenxiao XIAO ; Xinzhu ZHOU ; Lisha MO ; Shiwen KE ; Guoshuang ZHU ; Liangji LIU
Journal of Traditional Chinese Medicine 2024;65(13):1383-1391
ObjectiveTo investigate the possible mechanism of Wenfei Huaxian Decoction (温肺化纤汤) in treatment of pulmonary fibrosis in systemic sclerosis-associated interstitial lung disease (SSc-ILD). MethodsSixty C3H/He female rats were randomly divided into a control group, a model group, a pirfenidone group, and low-, medium-, and high-dose Wenfei Huaxian Decoction groups. The SSc-ILD model mice was established by subcutaneous injection of bleomycin solution 0.04 mg/d into the back of mice for 28 days in all groups but the control group. After successful modelling, the pirfenidone group was given pirfenidone capsule 300 mg/(kg·d) by gavage, the low-, medium- and high-dose Wenfei Huaxian Decoction groups were given Wenfei Huaxian Decoction 7.81, 15.62, and 31.24 g/(kg·d) by gavage, respectively, and the control group as well as the model group were given normal saline 0.1 ml/10 g by gavage, for a total of 21 days. At the end of the intervention, HE staining and Masson staining were used to observe the pathological changes in the skin and lung tissues; the hydroxyproline content of the skin and lung tissues was detected; the protein expression levels of endoplasmic reticulum stress-related proteins glucose-regulated protein 78 (BIP) and C/EBP homologous protein (CHOP) as well as those of nuclear factor kappa B (NF-κB) pathway p65 were measured by western blot; ELISA was performed to determine the expression levels of interferon gamma (IFN-γ), interleukin 6 (IL-6) and tumour necrosis factor alpha (TNF-α) in serum of rats. ResultsThe results of HE and Masson staining indicated that compared with the control group, the dermis significantly thickened, the number of collagen fibers significantly enlarged, and the number of inflammatory cells significantly increased in the model group; the lung tissue showed a marked inflammatory cellular response with massive collagen fibre proliferation with inflammatory cell infiltration. Compared with the model group, the skin tissue and lung tissue collagen fibre proliferation significantly reduced and inflammatory cell infiltration reduced in the pirfenidone group and all dose groups of Wenfei Huaxian Decoction, and the effects of pirfenidone group and Wenfei Huaxian Decoction medium- and high-dose groups were basically comparable. Compared with the model group, the content of hydroxyproline in skin and lung tissue, the serum level of IFN-γ, IL-6 and TNF-α, and the expression levels of BIP and CHOP protein in lung tissue increased in model group (P<0.05). Compared with model group, the content of hydroxyproline in skin tissue of pirfenidone group, low-and medium-dose Wenfei Huaxian Decoction groups decreased, and the content of hydroxyproline in lung tissue of medium-dose Wenfei Huaxian Decoction group decreased. The serum level of IFN-γ, IL-6, TNF-α and the expression levels of BIP, CHOP and p65 protein in lung tissue of rats in pirfenidone group and high-dose Wenfei Huaxian Decoction group decreased (P<0.05). The content of hydroxyproline in lung tissue of medium-dose Wenfei Huaxian Decoction group was significantly lower than that of low-dose and high-dose Wenfei Huaxian Decoction group, and the serum level of IFN-γ, IL-6, TNF-α in low- and medium-dose Wenfei Huaxian Decoction group were higher than those in high-dose Wenfei Huaxian Decoction group. The expression level of BIP protein in high-dose group was significantly lower than that in low- and medium-dose Wenfei Huaxian Decoction groups (P<0.05). ConclusionWenfei Huaxian Decoction can improve the skin and lung fibrosis of SSc-ILD rats, which may act through anti-inflammation, inhibition of NF-κB pathway, and then inhibition of endoplasmic reticulum stress, which ultimately blocked the fibrotic process.
6.Inhibitory effect of small-molecule compound AM679 targeting elongation-factor binding protein 2 on hepatitis B virus in vitro
Huijing FANG ; Jinyuan CAI ; Xiaoxue HOU ; Jiali SONG ; Linya PENG ; Chuanlong ZHU
Chinese Journal of Hepatology 2024;32(4):318-324
Objective:To explore the antiviral activity of the small-molecule compound AM679 in hepatitis B virus (HBV) replication and infection cell models.Methods:The positive regulatory effect of AM679 on EFTUD2 expression was validated by qPCR and Western blotting. HepAD38 and HepG2-NTCP cells were treated with AM679 (0.5, 1, and 2 nmol/L). Negative control, positive control, and AM679 combined with the entecavir group were set up. HBV DNA intra-and extracellularly, as well as the expression levels of intracellular HBV total RNAs and 3.5kb-RNA changes, were detected with qPCR. Hepatitis B surface antigen (HBsAg) and hepatitis B e antigen (HBeAg) levels were measured in the cell supernatant by an enzyme-linked immunosorbent assay (ELISA). The t-test method was used for the statistical analysis of the mean difference between groups.Results:EFTUD2 mRNA and protein expression levels were significantly increased in HepAD38 and HepG2-NTCP cells following AM679 treatment, with a statistically significant difference ( P ?0.001). Intra-and extracellular indicators such as HBV DNA, HBV RNAs, HBV 3.5kb-RNA, HBsAg, and HBeAg were decreased to varying degrees in both cell models, and the decrease in these indicators was more pronounced with the increase in AM679 concentration and prolonged treatment duration, while the combined use of AM679 and entecavir had a more significant antiviral effect. The HBV DNA inhibition rates in the supernatant of HepAD38 cells with the use of 2 nmol/L AM679 were 21% and 48% on days three and nine, respectively. The AM679 combined with the ETV treatment group had the most significant inhibitory effect (62%), with a P ?0.01. More active HBV replication was observed after silencing EFTUD2, while the antiviral activity of AM679 was significantly weakened. Conclusion:AM679 exerts anti-HBV activity in vitro by targeting the regulation of EFTUD2 expression.
7.Research on image segmentation of acute pancreatitis based on attention mechanism
Hong DENG ; Jiali XIAO ; Wen FENG ; Yuanzhong ZHU ; Bo XIAO ; Wenjing HE
International Journal of Biomedical Engineering 2024;47(2):141-148
Objective:To assess the efficacy of different fusion strategies involving the convolutional block attention module (CBAM) and Unet for automatic pancreas segmentation in enhanced CT images of patients with acute pancreatitis.Methods:A retrospective analysis was conducted on 1 158 patients with acute pancreatitis admitted to the Affiliated Hospital of North Sichuan Medical College between January 1st, 2016 and July 30th, 2021. Among them, 141 patients with first-episode acute pancreatitis were randomly categorized into mild, moderate, and severe cases. The test set comprised 5 mild and 15 severe cases, while the remaining 126 cases were used for training. Within the training set, 20% of the data was randomly allocated as the validation set. Different fusion paths of the CBAM and Unet networks were trained, utilizing the Dice similarity coefficient, Hausdorff distance (HD), and pixel accuracy (PA) as evaluation metrics. The model demonstrating the best performance on the validation set was selected and evaluated on the test set. Additionally, the Unet model was combined with the attention gate attention mechanism (AttentionUnet) in the skip connection, and the ResBlock replaced the original convolution module (ResUnet) in the Unet network. Moreover, the skip connection branch module of feature extraction was integrated with CBAM (ResUnet_CBAM) for comparison.Results:Unet_CBAM achieved better results on the test set with a Dice value of 80.06%, a HD value of 3.765 9 and a PA value of 0.992 3, all surpassing other fusion strategies. The segmentation accuracy of the pancreatic region in CT images of acute pancreatitis patients was notably enhanced compared to Unet and its related variant networks.Conclusions:The Unet network integrated into CBAM after skip connection can better perform pancreatic segmentation on enhanced CT images of patients with acute pancreatitis and can effectively improve the efficiency of relevant personnel in pancreatic segmentation on enhanced CT images of patients with acute pancreatitis.
8.Spatial and weighted gene co-expression analysis revealed the mechanism of cross-species ischemic heart failure
Zhenchun ZHANG ; Yongwei LI ; Yating WU ; Laihai ZHANG ; Haiyan WU ; Jiali XIE ; Hongming ZHU
Chinese Journal of Arteriosclerosis 2024;32(4):310-318
Aim To reveal the mechanism of cross-species ischemic heart failure from the perspective of spatial and gene co-expression networks.Methods GSE210374 and GSE57338 high-throughput sequencing datas were re-trieved from the national center for biotechnology information gene expression database(NCBI-GEO),and R language soft-ware packages was used to analyze and screen differentially expressed genes(DEG)in different myocardial regions of myo-cardial infarction rats,as well as DEG of myocardial samples from patients with ischemic heart failure and healthy controls,and the regional expression of common genes was analyzed.Weighted gene co-expression network analysis(WGCNA)was used to screen the genes related to myocardial infarction and to carry out enrichment analysis,protein-protein interac-tion network(PPI)was constructed to screen core genes(HG).Results A total of 4 835 differentially expressed genes were screened out in myocardial infarction rats and normal controls,and 51 differentially expressed genes were screened out in ischemic heart failure patients and normal control samples,which revealed representative gene sets in the left ventricular myocardial infarction area(I area),border area(BZ area),and remote area(R area)after myocardial in-farction.Spatial expression analysis revealed that there were 20 co-expressed genes in each myocardial region,16 of which were expressed in all three regions,the number of genes specifically expressed in I,BZ and R regions were 2,0 and 2,respectively.Enrichment analysis showed that the functions of co-expressed genes were different in different region.The I and BZ regions were related to collagen fiber assembly,stress-induced cardiomyocyte hypertrophy,down-regulation of c-Jun amino terminal kinase(JNK signal)and cell proliferation,and complement signaling pathways;The I and R regions were enriched in the binding of Wnt and collagen;As a non-ischemic distal R region,the co-expressed genes were signifi-cantly enriched in the extracellular matrix for functions such as compressive resistance,cytolysis and inhibition of T cell proliferation.Furthermore,it was worth noting that the products of co-expressed genes in the three regions were mostly lo-cated in the extracellular space and extracellular matrix,suggesting that there may be active cellular secretion and interac-tion regulation.Further PPI analysis suggested that asporin(ASPN),osteoglycin(OGN)and collagentype ⅩⅥ alpha chain(COL14A1)gene might be the core genes of the mechanism mentioned above.Conclusions The common mechanism of ischemic heart failure in rats and human involves multiple signaling pathways such as complement and coagu-lation cascade signaling and Wnt;which may be closely related to cell apoptosis mediated by extracellular matrix and exo-somes;ASPN,OGN,and COL14A1 may be the core genes.This work is expected to provide spatial and pathway refer-ence for the selection of intervention targets and pathway in the transformation research related to ischemic heart failure.
9.Correlation Analysis Between Anti-cerebral Ischemia Oxidative Damage and Contents of Active Components in Characteristic Processed Products with Porcine Cardiac Blood and Other Processed Products of Salviae Miltiorrhizae Radix et Rhizoma from Menghe Medical School
Zhen ZENG ; Yuanpei LIAN ; Jiali CAI ; Chunyan YIN ; Dijun WANG ; Li ZHU ; Chanming LIU ; Wei HUANG ; Xiaojing YAN
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(15):162-171
ObjectiveTo analyze the correlation between 11 small molecule active components and 1 protein component of characteristic processed products with porcine cardiac blood and other products of Salviae Miltiorrhizae Radix et Rhizoma(SMRR) from Menghe medical school and anti-cerebral ischemic oxidative damage, and to identify its key component markers of characteristic processed products with porcine cardiac blood for anti-cerebral ischemic oxidative damage. MethodHigh performance liquid chromatography(HPLC) was established to simultaneously determine the contents of 11 active ingredients in SMRR and its processed products[processed with porcine cardiac blood, porcine blood, wine and transferrin(Tf) in porcine cardiac blood], and the content of Tf in different processed products of SMRR was detected by enzyme-linked immunosorbent assay(ELISA). Furthermore, A zebrafish ischemic stroke model was constructed to evaluate the effects of different processed products of SMRR on the behavioral trajectory of cerebral ischemic zebrafish, the neuronal damage of transgenic zebrafish Tg(elavl3:eGFP) brain, as well as the levels of malondialdehyde(MDA) and superoxide dismutase(SOD) in the brain tissues. The hippocampal neurons oxygen-glucose deprivation/reoxygenation(OGD/R)-induced ischemia-hypoxia model was constructed to evaluate the effects of different processed products of SMRR on oxidative damage of neuronal cells by taking lactate dehydrogenase(LDH), reactive oxygen species(ROS), MDA and SOD as indexes. Finally, principal component analysis(PCA), partial least squares-discriminant analysis(PLS-DA) and Spearman correlation analysis were used to analyze the 11 small molecule active components and 1 protein component with efficacy indicators, in order to screen the key components of the characteristic processed products with porcine cardiac blood for cerebral ischemic oxidative damage. ResultCompared with the raw products, the contents of water-soluble and fat-soluble components in processed products of SMRR increased to different degrees, while the content of salvianolic acid A decreased. Compared with the wine-processed products, the contents of salvianolic acid B, danshensu, rosmarinic acid and other components in the porcine cardiac blood-processed products, porcine blood-processed products, Tf-processed products were increased, while the content of salvianolic acid A was decreased. ELISA results showed that there was no significant difference in Tf content between the porcine cardiac blood-processed products, porcine blood-processed products, Tf-processed products. Pharmacological results showed that different processed products of SMRR could improve the behavioral deficits, brain neuronal injury and oxidative stress after ischemic stroke in zebrafish, and the effect of the porcine cardiac blood-processed products was most pronounced. PCA results showed that salvianolic acid B, salvianolic acid A, rosmarinic acid, lithospermic acid, danshensu, tanshinone ⅡA, caffeic acid, cryptotanshinone and tanshinone Ⅰ were the main contributing components of SMRR and its processed products. And the results of correlation analysis showed that the contents of cryptotanshinone, rosmarinic acid, caffeic acid, dihydrotanshinone Ⅰ, salvianolic acid B, tanshinone ⅡA and tanshinone Ⅰ were negatively correlated with MDA level in zebrafish brain tissue, while the contents of lithospermic acid, protocatechuic aldehyde, rosmarinic acid, dihydrotanshinone Ⅰ, salvianolic acid B and Tf were positively correlated with SOD level, and the contents of rosmarinic acid, caffeic acid, dihydrotanshinone Ⅰ, salvianolic acid B, tanshinone ⅡA, tanshinone Ⅰ, danshensu, Tf were positively correlated with neuronal fluorescence intensity in the zebrafish brain. And the contents of lithospermic acid, protocatechuic aldehyde, rosmarinic acid, dihydrotanshinone Ⅰ, salvianolic acid B, tanshinone ⅡA and Tf were negatively correlated with LDH, ROS and MDA levels and positively correlated with SOD level. ConclusionThere are differences in the anti-ischemic oxidative damage effects of SMRR and its different processed products, among which the porcine cardiac blood-processed products has the strongest effect on improving oxidative damage, which may be related to the content changes of salvianolic acid B, danshensu, rosmarinic acid and other components. This study can provide a basis for clarifying the quality markers of SMRR processed with porcine cardiac blood for cerebral ischemia and elucidating its processing mechanism.
10.Factors Influencing Inpatient Costs for Patients Undergoing Surgery for Intrauterine Lesions under DRG Payment
Yutong WANG ; Weiguo ZHU ; Xueqin SUN ; Jiali TONG ; Jingya ZHOU ; Qing ZHAO ; Bocheng LI ; Wei ZHANG ; Xiaokun LIU ; Rui DONG ; Chen XIE ; Ding HAN
Medical Journal of Peking Union Medical College Hospital 2024;15(5):1069-1076
To analyze the factors affecting the cost of hospitalization for patients and provide insights using the intrauterine lesion surgery group (DRG code NE19) as an example. This study was a retrospective cross-sectional study, with data from the first page of medical records of patients enrolled under NE19 at a comprehensive tertiary hospital in Beijing from March 15, 2022 to November 30, 2023. Influence factor selection and multifactorial linear regression analysis were conducted with hospitalization cost as the dependent variable, and patient's basic information, treatment information and key concern factors as independent variables. The profit and loss of medical records containing key factors and differences in indicators of hospitalization cost structure were analyzed in the context of clinical practice. A total of 2213 valid medical records (all female patients) were included, with patients predominantly young and middle-aged women under 45 years of age (72.12%), and with 931 day surgery medical records (42.07%). The diagnosis records included 334(15.09%) multiple uterine leiomyomas, and 246(11.12%) pelvic adhesions. A total of 150(6.78%) medical records involved ovary- and tubal-related surgeries or manipulations, with 160(7.23%) main operations being laparoscopic hysterectomy of diseased uterine lesions and 38(1.72%) mechanical rotational excision of abnormal uterine tissue using transhysteroscopy. Linear regression analysis showed that whether or not ovarian and tubal surgical operations were involved ( The NE19 group of hospitals in the study had a high loss rate, and factors such as the severity of the patient's condition and the use of new technologies affected hospitalization costs, suggesting that there is room for further optimization of the existing grouping scheme. Tiered payment standards can be set up for different tiers of healthcare institutions, and a sound and optimized exclusion mechanism can be used to promote the development of new technologies. The internal management of hospitals should encourage the development of daytime surgery to improve the efficiency of medical services.


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