Effect of Tongluo Juanbi Granules on Inflammatory Injury and Apoptosis of Osteoarthritis Based on TLR4/MyD88/NF-κB Signaling Pathway / 中国实验方剂学杂志

ObjectiveTo investigate the effects of Tongluo Juanbi granules on chondrocyte apoptosis and Toll-like receptor 4 （TLR4）/myeloid differentiation factor 88 （MyD88）/nuclear factor-κB （NF-κB） signaling pathway of rabbits with knee osteoarthritis （KOA） and study the mechanism of Tongluo Juanbi granules in the prevention and treatment of KOA. MethodThirty New Zealand rabbits were randomly assigned to the following five groups （n=6）： sham group， model group， low-dose and high-dose groups of Tongluo Juanbi granules （4.1 and 8.2 g·kg-1·d-1）， and celecoxib group （10.9 mg·kg-1·d-1）. The KOA model was established by destabilization of the medial meniscus （DMM） for six weeks. Six weeks after the modeling， the drug was given once a day for eight weeks. The pathological changes of cartilago articularis were observed by hematoxylin-eosin （HE） staining and Safranin O-Fast Green staining. Terminal deoxynucleotidyl transferase dUTP nick end labeling （TUNEL） staining was performed to detect chondrocyte apoptosis. Enzyme-linked immunosorbent assay （ELISA） was used to detect the contents of interleukin-1β （IL-1β） and tumor necrosis factor-α （TNF-α） in synovial fluid. The mRNA and protein expression levels of genes related to the TLR4/MyD88/NF-κB signaling pathway were detected by real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） and Western blot， respectively. ResultCompared with the sham group， the cartilago articularis of the model group significantly degenerated. Mankin's score was increased （P<0.01）， and the contents of IL-1β and TNF-α in synovial fluid were increased （P<0.01）. The number of apoptosis of chondrocytes was increased （P<0.01）. The mRNA and protein expressions of TLR4， MyD88， and NF-κB p65 in cartilage tissue were up-regulated （P<0.01）， while the mRNA and protein expressions of Bcl-2 were down-regulated （P<0.01）. Compared with the model group， chondrocyte degeneration in both low-dose and high-dose groups of Tongluo Juanbi granules was improved， and Mankin's score was decreased （P<0.01）. The contents of IL-1β and TNF-α were decreased （P<0.01）， and the number of apoptosis of chondrocytes was decreased （P<0.01）. The mRNA and protein expressions of TLR4， MyD88， and NF-κB p65 in cartilage tissue were down-regulated （P<0.01）， while the mRNA and protein expressions of Bcl-2 were up-regulated （P<0.01）. In addition， in the above observation indicators， the high-dose group of Tongluo Juanbi granules was significantly superior to the low-dose group of Tongluo Juanbi granules. ConclusionTongluo Juanbi granules could inhibit chondrocyte apoptosis in rabbits with KOA and improve cartilage degeneration， which may be related to inhibiting inflammatory responses mediated by TLR4/MyD88/NF-κB signaling pathway.

Targeting FAPα-positive lymph node metastatic tumor cells suppresses colorectal cancer metastasis

Lymphatic metastasis is the main metastatic route for colorectal cancer, which increases the risk of cancer recurrence and distant metastasis. The properties of the lymph node metastatic colorectal cancer (LNM-CRC) cells are poorly understood, and effective therapies are still lacking. Here, we found that hypoxia-induced fibroblast activation protein alpha (FAPα) expression in LNM-CRC cells. Gain- or loss-function experiments demonstrated that FAPα enhanced tumor cell migration, invasion, epithelial-mesenchymal transition, stemness, and lymphangiogenesis via activation of the STAT3 pathway. In addition, FAPα in tumor cells induced extracellular matrix remodeling and established an immunosuppressive environment via recruiting regulatory T cells, to promote colorectal cancer lymph node metastasis (CRCLNM). Z-GP-DAVLBH, a FAPα-activated prodrug, inhibited CRCLNM by targeting FAPα-positive LNM-CRC cells. Our study highlights the role of FAPα in tumor cells in CRCLNM and provides a potential therapeutic target and promising strategy for CRCLNM.

Intervention effect of Chuanxiong-Chishao herb pair on circRNA/lncRNA expression profile in a myocardial infarction-atherosclerosis model / 中国中药杂志

This study aimed to explore the intervention effect of Chuanxiong-Chishao herb pair(CX-CS) on a myocardial infarction-atherosclerosis(MI-AS) mouse model and investigate its effect on the expression profile of circular RNAs(circRNAs)/long non-coding RNAs(lncRNAs) in ischemic myocardium and aorta. Sixty male ApoE~(-/-) mice were randomly assigned to a model group, high-, medium-, and low-dose CX-CS groups(7.8, 3.9, and 1.95 g·kg~(-1)), and a positive drug group(metoprolol 26 mg·kg~(-1) and simvastatin 5.2 mg·kg~(-1)), with 12 mice in each group. Male C57BL/6J mice were assigned to the sham group. The mice in the model group and the groups with drug intervention were fed on a high-fat diet for 10 weeks, followed by anterior descending coronary artery ligation. After that, the mice were fed on a high-fat diet for another two weeks to induce the MI-AS model. The mice in the sham group received normal feed, followed by sham surgery without coronary artery ligation. Mice in the groups with drug intervention received CX-CS or positive drug by gavage for four weeks from the 9th week of high-fat feeding, and those in the model group and the sham group received an equal volume of normal saline. Whole transcriptome sequencing was performed on the heart and aorta tissues of the medium-dose CX-CS group, the model group, and the sham group after administration. The results showed that the medium-and high-dose CX-CS groups showed improved cardiac function and reduced myocardial fibrosis area, and the medium-dose CX-CS group showed significantly reduced plaque area. CX-CS treatment could reverse the expression of circRNA＿07227 and circRNA＿11464 in the aorta of AS model and circRNA expression(such as circRNA＿11505) in the heart of the MI model. Differentially expressed circRNAs between the CX-CS-treated mice and the model mice were mainly enriched in lipid synthesis, lipid metabolism, lipid transport, inflammation, and angiogenesis in the aorta, and in angiogenesis, blood pressure regulation, and other processes in the heart. CX-CS treatment could reverse the expression of lncRNAs such as ENSMUST00000162209 in the aorta of the AS model and TCONS＿00002123 in the heart of the MI model. Differentially expressed lncRNAs between the CX-CS-treated mice and model mice were mainly enriched in lipid metabolism, angiogenesis, autophagy, apoptosis, and iron death in the aorta, and in angiogenesis, autophagy, and iron death in the heart. In summary, CX-CS can regulate the expression of a variety of circRNAs and lncRNAs, and its intervention mechanism in coronary heart disease may be related to the regulation of angiogenesis and inflammation in ischemic myocardium, as well as lipid metabolism, lipid transport, inflammation, angiogenesis in AS aorta.

Significance of high expression of C5orf46 in gastric cancer and potential intervention of tarditional Chinese medicine based on bioinformatics, molecular docking, and cell experiments / 中国中药杂志

This study aims to investigate the expression, prognosis, and clinical significance of C5orf46 in gastric cancer and to study the interaction between the active components of C5orf46 and tarditional Chinese medicine. The ggplot2 package was utilized for differential expression analysis of C5orf46 in gastric cancer tissues and normal tissues. The survival package was used for survival analysis, univariate regression analysis, and multivariate regression analysis. Nomogram analysis was used to assess the connection between C5orf46 expression in gastric cancer and overall survival. The abundance of tumor-infiltrating lymphocytes was calculated by GSVA package. Coremine database, Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP) database, and PubChem database were used to search the potential components corresponding to C5orf46 gene and tarditional Chinese medicine. Molecular docking was performed to explore the binding affinity of potential components to C5orf46. Cell experiments were performed to explore the expression of C5orf46 gene in cells of the blank group, model group, and drug administration groups. As compared with normal tissues, C5orf46 expression was higher in gastric cancer tissues, which had more significant predictive effects in the early stages(T2, N0, and M0). The more advanced the tumor node metastasis(TNM) stage, the higher the C5orf46 expression and the lower the probability of survival of patients with gastric cancer. The expression of C5orf46 positively correlated with the helper T cells1 in gastric cancer and the macrophage infiltration level in gastric cancer, and negatively correlated with B cells, central memory T cells, helper T cells 17, and follicular helper T cells. Seven potential components of C5orf46 were obtained, and three active components were obtained after the screening, which matched five tarditional Chinese medicines, namely, Sojae Semen Nigrum, Jujubae Fructus, Trichosanthis Fructus, Silybi Fructus, and Bambusae Concretio Silicea. Molecular docking revealed that sialic acid and adeno-sine monophosphate(AMP) had a good binding ability to C5orf46. The results of real-time quantitative polymerase chain reaction(RT-qPCR) and Western blot showed that, as compared with the model group, the mRNA and protein expression levels of C5orf46 were significantly lower in the drug administration groups. The lowest expression level was found at the concentration of 40 μmol·L~(-1). The results of this study provide ideas for the clinical development of traditional Chinese medicine compounds for the treatment of gastric cancer as well as other cancers.

Influence of E-cadherin methylation on prognosis in children with acute lymphoblastic leukemia / 中国当代儿科杂志

OBJECTIVES@#To study the significance of E-cadherin and the association between E-cadherin methylation status and prognosis in children with acute lymphoblastic leukemia (ALL) by examining the mRNA and protein expression of E-cadherin and its gene methylation status in bone marrow mononuclear cells of children with ALL.@*METHODS@#The samples of 5 mL bone marrow blood were collected from 42 children with ALL who were diagnosed for the first time at diagnosis (pre-treatment group) and on day 33 of induction chemotherapy (post-treatment group). RT-qPCR, Western blot, and methylation-specific PCR were used to measure the mRNA and protein expression of E-cadherin and the methylation level of the E-cadherin gene. The changes in each index after induction chemotherapy were compared.@*RESULTS@#The mRNA and protein expression levels of E-cadherin in the post-treatment group were significantly higher than those in the pre-treatment group (P<0.05), while the positive rate of E-cadherin gene methylation in the post-treatment group was significantly lower than that in the pre-treatment group (P<0.05). At the end of the test, the children with negative methylation had significantly higher overall survival rate and event-free survival rate than those with positive methylation (P<0.05).@*CONCLUSIONS@#E-cadherin expression is associated with the development of ALL in children, and its decreased expression and increased methylation level may indicate a poor prognosis.

Immunogenicity and safety of revaccination of 23-valent pneumococcal polysaccharide vaccine in people aged 60 years and above / 中华流行病学杂志

Objective: To evaluate the immunogenicity and safety of revaccination of 23-valent pneumococcal polysaccharide vaccine (PPV23) in elderly people aged ≥60 years. Methods: The elderly aged ≥60 years with 1 dose of PPV23 vaccination were selected as revaccination group and those without history of pneumococcal vaccine immunization were selected as the first vaccination group. One dose of PPV23 was administered to both groups, and the first blood samples were collected before vaccination while the second blood samples were collected on day 28-40 after vaccination. ELISA was used to detect the concentrations of anti-specific serotype Streptococcus pneumoniae podocyte polysaccharide immunoglobulin G, and the safety of the vaccination was evaluated after 30 days. Results: The geometric mean concentration (GMC) of antibody to 23 serotypes before the vaccination (0.73-13.73 μg/ml) was higher in revaccination group than in the first vaccination group (0.39-7.53 μg/ml), the GMC after the vaccination (1.42-31.65 μg/ml) was higher than that before the vaccination (0.73-13.73 μg/ml) in the revaccination group, and the GMC after the vaccination (1.62-43.76 μg/ml) was higher than that before the vaccination (0.39-7.53 μg/ml) in the first vaccination group; the geometric mean growth multiple in revaccination group (2.16-3.60) was lower than that in the first vaccination group (3.86-16.13); The mean 2-fold antibody growth rate was lower in revaccination group (53.68%, 95%CI: 52.30%-55.06%) than in the first vaccination group (93.16%, 95%CI: 92.18%- 94.15%), all differences were significant (P<0.001). After the vaccination, 13 serotypes of GMC were higher in the first vaccination group than in revaccination group (P<0.001), the differences were not significant for 10 serotypes of GMC (P>0.05). The incidence of local adverse reaction was 19.20% and 13.27% in revaccination group and the first vaccination group, respectively (P=0.174). Conclusions: The antibody level in ≥60 years people who received one dose of PPV23 after a 5-year interval was still higher than that in unvaccinated people. The antibody level decreased after 5 years of the first vaccination, and the antibody level could be rapidly increased by one more dose vaccination, but the overall immune response was lower than that of the first vaccination; revaccination with PPV23 has a good safety.

The Prognostic Value of Prognostic Nutritional Index Combined with D-dimer in Patients with Diffuse Large B-Cell Lymphoma / 中国实验血液学杂志

OBJECTIVE@#To explore the effects of prognostic nutritional index (PNI) combined with D-dimer on the prognosis of patients with newly diagnosed diffuse large B-cell lymphoma (DLBCL).@*METHODS@#The clinical data of 73 DLBCL patients at initial diagnosis were retrospectively evaluated, and the optimal cut-off point of PNI and D-dimer were determined by ROC curve. The overall survival (OS) rate and progression-free survival (PFS) rate in different subgroups were compared using Kaplan-Meier survival curves. Univariate and multivariate Cox regression analysis was performed to identify the factors associated with OS.@*RESULTS@#Compared with the low PNI group (PNI<44.775), the high PNI group (PNI≥44.775) had better OS (P =0.022) and PFS (P =0.029), the 2-year OS rates of the two groups were 55.6% and 78.3% respectively (P =0.041). Compared with the high D-dimer group (D-dimer≥0.835), the low D-dimer group (D-dimer<0.835) had better OS (P <0.001) and PFS (P <0.001), the 2-year OS rates of the two groups were 51.4% and 86.8% respectively (P =0.001). Meanwhile, patients in the high PNI+ low D-dimer group had better OS (P =0.003) and PFS (P <0.001) than the other three groups, the 2-year OS rate was statistically different from the other three groups (P <0.05). The multivariate analysis revealed that NCCN-IPI (HR =2.083, 95%CI : 1.034-4.196, P =0.040), PNI (HR =0.267, 95%CI : 0.076-0.940, P =0.040) and PNI+D-dimer (HR =9.082, 95%CI : 1.329-62.079, P =0.024) were the independent risk factors affecting OS in patients with DLBCL. Subgroup analysis showed that PNI, D-dimer, and PNI combined with D-dimer could improve the prognostic stratification in low and low-intermediate risk DLBCL patients.@*CONCLUSION@#High PNI, low D-dimer and combination of high PNI and low D-dimer at initial diagnosis suggest a better prognosis in DLBCL patients.

Endothelial METRNL determines circulating METRNL level and maintains endothelial function against atherosclerosis

METRNL is a recently identified secreted protein with emerging functions. This study is to find major cellular source of circulating METRNL and to determine METRNL novel function. Here, we show METRNL is abundant in human and mouse vascular endothelium and released by endothelial cells using endoplasmic reticulum-Golgi apparatus pathway. By creating endothelial cell-specific Metrnl knockout mice, combined with bone marrow transplantation to produce bone marrow-specific deletion of Metrnl, we demonstrate that most of circulating METRNL (approximately 75%) originates from the endothelial cells. Both endothelial and circulating METRNL decrease in atherosclerosis mice and patients. By generating endothelial cell-specific Metrnl knockout in apolipoprotein E-deficient mice, combined with bone marrow-specific deletion of Metrnl in apolipoprotein E-deficient mice, we further demonstrate that endothelial METRNL deficiency accelerates atherosclerosis. Mechanically, endothelial METRNL deficiency causes vascular endothelial dysfunction including vasodilation impairment via reducing eNOS phosphorylation at Ser1177 and inflammation activation via enhancing NFκB pathway, which promotes the susceptibility of atherosclerosis. Exogenous METRNL rescues METRNL deficiency induced endothelial dysfunction. These findings reveal that METRNL is a new endothelial substance not only determining the circulating METRNL level but also regulating endothelial function for vascular health and disease. METRNL is a therapeutic target against endothelial dysfunction and atherosclerosis.

Effectiveness of Bian stone warming and ironing combined with aromatherapy on postpartum urinary retention among lying-in women with painless delivery / 预防医学

Objective@#To evaluate the effectiveness of Bian stone warming and ironing combined with aromatherapy on postpartum urinary retention among lying-in women with painless delivery, so as to provide the reference for preventing postpartum urinary retention after painless delivery.@*Methods@#Lying-in women who underwent painless delivery in the Hangzhou Women' s Hospital were randomly assigned into the intervention and control group. Participants in the intervention group were given Bian stone warming and ironing combined with essential oil aromatherapy, while participants in the control group were given routine nursing care. The first postpartum urination and urinary retention were recorded, nursing satisfaction was investigated using Newcastle Satisfaction with Nursing Scale, the quality of life was evaluated using The World Health Organization Quality of Life-BREF, and these indicators were compared between the two groups.@*Results@#There were 92 participants in the intervention group, with a mean age of (26.51±1.31) years and mean gestational age of (38.11±0.55) weeks, and 86 participants in the control group, with a mean age of (26.61±1.24) years and mean gestational age of (38.28±0.72) weeks. There was no statistically significant difference in the general data between the two groups (P>0.05). The time of first urination in the intervention group was shorter than that in the control group [(2.91±1.02) h vs. (3.76±1.68) h], the first postpartum urine volume was more than that in the control group [(160.56±21.03) mL vs. (142.43±18.42) mL], the residual urine volume of the bladder after the first urination was less than that in the control group [(73.20±17.03) mL vs. (85.46±20.24) mL], the incidence of urinary retention was lower than that in the control group (3.26% vs. 10.47%), nursing satisfaction was higher than that in the control group, and the increase in scores of all dimensions of quality of life was greater than that in the control group, with statistically significant differences (all P<0.05). @*Conclusions@#Bian stone warming and ironing therapy combined with aromatherapy may effectively reduce the incidence of postpartum urinary retention, and improve nursing satisfaction and quality of life among lying-in women after painless delivery.

Automatic segmentation of organs at risk in head and neck carcinoma from radiation therapy using multi-scale fusion and attention based mechanisms / 中华放射肿瘤学杂志

Objective:To develop a multi-scale fusion and attention mechanism based image automatic segmentation method of organs at risk (OAR) from head and neck carcinoma radiotherapy.Methods:We proposed a new OAR segmentation method for medical images of heads and necks based on the U-Net convolution neural network. Spatial and channel squeeze excitation (csSE) attention block were combined with the U-Net, aiming to enhance the feature expression ability. We also proposed a multi-scale block in the U-Net encoding stage to supplement characteristic information. Dice similarity coefficient (DSC) and 95% Hausdorff distance (HD) were used as evaluation criteria for deep learning performance.Results:The segmentation of 22 OAR in the head and neck was performed according to the medical image computing computer assisted intervention (MICCAI) StructSeg2019 dataset. The proposed method improved the average segmentation accuracy by 3%-6% compared with existing methods. The average DSC in the segmentation of 22 OAR in the head and neck was 78.90% and the average 95%HD was 6.23 mm.Conclusion:Automatic segmentation of OAR from the head and neck CT using multi-scale fusion and attention mechanism achieves high segmentation accuracy, which is promising for enhancing the accuracy and efficiency of radiotherapy in clinical practice.

Hepatotoxicity and mechanism of Rhododendri Mollis Flos based on zebrafish model / 中国中药杂志

This study used the zebrafish model to explore the hepatotoxicity of Rhododendri Mollis Flos(RMF). The mortality was calculated according to the number of the survival of zebrafish larvae 4 days after fertilization under different concentration of RMF, and the dose-toxicity curve was fitted to preliminarily evaluate the toxicity of RMF. The liver phenotypes under the sublethal concentration of RMF in the treatment group and the blank control group were observed by hematoxylin-eosin(HE) staining and acridine orange(AO) staining. Meanwhile, the activities of alanine aminotransferase(ALT) and aspartate aminotransferase(AST) were determined to confirm the hepatotoxicity of RMF. Real-time quantitative polymerase chain reaction(real-time PCR) and Western blot were used to determine the expressions of genes and proteins in zebrafish larvae. Gas chromatography time-of-flight mass spectrometry(GC-TOF-MS) was used to conduct untargeted metabolomics testing to explore the mechanism. The results showed that the toxicity of RMF to zebrafish larvae was dose-dependent, with 1 100 μg·mL~(-1) of the absolute lethal concentration and 448 μg·mL~(-1) of sublethal concentration. The hepatocyte apoptosis and degeneration appeared in the zebrafish larvae under the sublethal concentration of RMF. The content of ALT and AST in zebrafish larvae at the end of the experiment was significantly increased in a dose-dependent manner. Under the sublethal concentration, the expressions of genes and proteins related to apoptosis in zebrafish larvae were significantly increased as compared with the blank control group. The results of untargeted metabolomics showed that the important metabolites related to the he-patotoxicity of RMF were mainly enriched in alanine, aspartic acid, glutamic acid, and other pathways. In conclusion, it is inferred that RMF has certain hepatotoxicity to zebrafish larvae, and its mechanism may be related to apoptosis.

Dryness-alleviating effect of processed Aurantii Fructus from Lingnan based on correlation of fecal metabolomics and dryness / 中国中药杂志

With the approach of untargeted metabolomics and correlation analysis, this study aimed to explore the mechanism of Aurantii Fructus from Lingnan region in alleviating dryness by analyzing the different effects of raw Aurantii Fructus(RAF) and processed Aurantii Fructus(PAF) on fecal endogenous metabolism in normal rats. Eighteen Sprague-Dawley(SD) rats were randomly divided into a control group(C), an RAF group(10 g·kg~(-1)), and a PAF group(10 g·kg~(-1)). After seven days of administration, the effects of RAF and PAF on dryness-related indexes were compared, including water intake, fecal water content, salivary secretion, the expression of AQP5, VIP, and 5-HT in the submandibular gland, as well as the expression of AQP3, VIP, and 5-HT in the colon. The fecal samples in each group were determined by LC-MS. Multivariate statistical analysis and Pearson correlation coefficient were used for screening the differential metabolites and metabolic pathways in alleviating dryness of RAF. The results indicated that both RAF and PAF showed certain dryness, and the dryness of RAF was more significant. Moreover, PAF could alleviate dryness of RAF to a certain extent by reducing the water intake, fecal water content, and the expression of AQP3, VIP, and 5-HT in the colon and increasing the salivary secretion and the levels of AQP5, VIP, and 5-HT in the submandibular gland. According to the analysis of fecal metabolomics, 99 and 58 metabolites related to dryness were found in RAF and PAF respectively, where 16 of them played an important role in alleviating dryness of RAF. Pathway analysis revealed that the mechanism of PAF in alleviating dryness of RAF was presumably related to the regulation of riboflavin metabolism, purine metabolism, arginine biosynthesis, pyrimidine metabolism, alanine metabolism, aspartate metabolism, glutamate metabolism, and retinol metabolism pathways. This study suggested that PAF might alleviate dryness of RAF by affecting the metabolic levels of the body, which provides a new basis for further clarifying the processing mechanism of PAF.

Changes in Notified Incidence of Pulmonary Tuberculosis in China, 2005-2020 / 生物医学与环境科学（英文）

OBJECTIVE@#To evaluate the trend of notified incidence of pulmonary tuberculosis (PTB) in China at different periods by population and region and to explore the effect of TB prevention and control in recent years.@*METHODS@#Using pooled data on TB cases reported by the TB Information Management Reporting System (TBIMS) from 2005 to 2020, we calculated the annual percentage change (APC) using the Joinpoint regression model.@*RESULTS@#From 2005 to 2020, a total of 16.2 million cases of PTB were reported in China, with an average notified incidence of 75.5 per 100,000 population. The age standardization rate (ASR) continued to decline from 116.9 (/100,000) in 2005 to 47.6 (/100,000) in 2020, with an average annual decrease of 5.6% [APC = -5.6, 95% confidence interval ( CI): -7.0 to -4.2]. The smallest decline occurred in 2011-2018 (APC = -3.4, 95% CI: -4.6 to -2.3) and the largest decrease in 2018-2020 (APC = -9.2, 95% CI: -16.4 to -1.3). From 2005 to 2020, the ASR in males (159.8 per 100,000 in 2005, 72.0 per 100,000 in 2020) was higher than that in females (62.2 per 100,000 in 2005, 32.3 per 100,000 in 2020), with an average annual decline of 6.0% for male and 4.9% for female. The average notified incidence was the highest among older adults (65 years and over) (182.3/100,000), with an average annual decline of 6.4%; children (0-14 years) were the lowest (4.8/100,000), with an average annual decline of 7.3%, but a significant increase of 3.3% between 2014 and 2020 (APC = 3.3, 95% CI: 1.4 to 5.2); middle-aged (35-64 years) decreased by 5.8%; and youth (15-34 years) decreased by an average annual rate of 4.2%. The average ASR in rural areas (81.3/100,000) is higher than that in urban areas (76.1/100,000). The average annual decline in rural areas was 4.5% and 6.3% in urban areas. South China had the highest average ASR (103.2/100,000), with an average annual decline of 5.9%, while North China had the lowest (56.5/100,000), with an average annual decline of 5.9%. The average ASR in the southwest was 95.3 (/100,000), with the smallest annual decline (APC = -4.5, 95% CI: -5.5 to -3.5); the average ASR in the Northwest China was 100.1 (/100,000), with the largest annual decline (APC = -6.4, 95% CI: -10.0 to -2.7); Central, Northeastern, and Eastern China declined by an average of 5.2%, 6.2%, and 6.1% per year, respectively.@*CONCLUSIONS@#From 2005 to 2020, the notified incidence of PTB in China continued to decline, falling by 55%. For high-risk groups such as males, older adults, high-burden areas in South, Southwest, and Northwest China, and rural regions, proactive screening should be strengthened to provide timely and effective anti-TB treatment and patient management services for confirmed cases. There is also a necessity to be vigilant about the upward trend of children in recent years, the specific reasons for which need to be further studied.

Clinical Significance of SFRP1 Gene Methylation in Patients with Childhood Acute Lymphoblastic Leukemia / 中国实验血液学杂志

OBJECTIVE@#To investigate the clinical significance of SFRP1 gene and its methylation in childhood acute lymphoblastic leukemia (ALL) .@*METHODS@#Methylation-specific PCR (MSP) was used to detect the methylation status of SFRP1 gene in bone marrow mononuclear cells of 43 children with newly diagnosed ALL before chemotherapy (primary group) and when the bone marrow reached complete remission d 46 after induction of remission chemotherapy (remission group), the expression of SFRP1 mRNA was detected by quantitative real-time polymerase chain reaction (qRT-PCR), the expression of SFRP1 protein was detected by Western blot, and clinical data of children were collected, the clinical significance of SFRP1 gene methylation in children with ALL was analyze.@*RESULTS@#The positive rate of SFRP1 gene promoter methylation in the primary group (44.19%) was significantly higher than that in the remission group (11.63%) (χ2=11.328, P<0.05). The relative expression levels of SFRP1 mRNA and protein in bone marrow mononuclear cells of children in the primary group were significantly lower than those in the remission group (P<0.05). Promoter methylation of SFRP1 gene was associated with risk level (χ2=15.613, P=0.000) and survival of children (χ2=6.561, P=0.010) in the primary group, children with SFRP1 hypermethylation had significantly increased risk and shortened event-free survival time, but no significant difference in other clinical data.@*CONCLUSION@#Hypermethylation of SFRP1 gene promoter may be involved in the development of childhood ALL, and its hypermethylation may be associated with poor prognosis.

Clinical evaluation of the efficacy against helicobacter pylori by amoxicillin from volume-based procurement and potassium amoxicillin clavulanate / 中国临床药理学与治疗学

AIM: To evaluate the clinical efficacy of amoxicillin from volume-based procurement (VBP) and potassium amoxicillin clavulanate in the eradication of helicobacter pylori (Hp) infection, providing basis for the selection of treatment programs. METHODS: Data from the patients who received Hp eradication therapy from May 2021 to May 2022 were recruited from the rational drug use management system. The data from the patients treated by amoxicillin (amoxicillin 1.0 g bid + bismuth potassium citrate 220 mg bid + esomeprazole 20 mg bid + clarithromycin 0.5 g bid, for 14 days) and potassium amoxicillin clavulanate (potassium amoxicillin clavulanate 0.914 g bid + bismuth potassium citrate 220 mg bid + esomeprazole 20 mg bid + clarithromycin 0.5 g bid, for 14 days) were selected and compared. RESULTS: A total of 171 cases were collected in the group treated by Amoxicillin program, and the eradication rate was 87.8% (150/171). A total of 69 cases were collected in the group of potassium amoxicillin clavulanate, and the eradication rate was 76.8% (53/69). There was no significant difference in baseline data between the two groups (P>0.05). There was a significant difference in clinical efficacy between the two groups (P< 0.05). In addition, the cost-effectiveness ratio (C/E) of the Amoxicillin treatment program was lower than that of the potassium amoxicillin clavulanate program CONCLUSION: The clinical efficacy of VBP Amoxicillin program in eradicating Hp infection is better than that of the potassium amoxicillin clavulanate program, which is worthy of clinical recommendation.

Pharmaceutical care of patients with antithrombotic therapy after transjugular intrahepatic portal shunt / 中国临床药理学与治疗学

AIM: To explore the role of clinical pharmacist in the treatment of patients with transjugular intrahepatic portosystemic shunt. METHODS: Clinical pharmacist participated in the treatment of a patient with repeated oral bleeding after transjugular intrahepatic portal shunt followed treatment with multiple antithrombotic drugs, which assisted the physician to diagnose and adjust the antithrombotic treatment plan as well as provided the patient with whole-process pharmaceutical care and online management. RESULTS: Based on the inquiry about the patient's past and current medical history and medication consumption, the pharmacist considered that there was weak correlation between oral hemorrhage and antithrombotic drugs and advised for dentist inspection. Thereafter, the patient was diagnosed with chronic gingivitis. The dosage of warfarin was adjusted, and the pharmacists managed it online after discharge to achieve stable INR of the patient. In the later online follow-up, an abnormal increase of INR was encountered, By asking about the history of medication, it was considered that the increase in INR was related to taking amoxicillin capsules. Therefore, the pharmacist suggested to stop amoxicillin capsule and to gradually adjust the dose of warfarin to the original level to improve the treatment. CONCLUSION: The involvement of clinical pharmacists in clinical treatment facilitates comprehensive pharmaceutical care of patients, which plays a positive role in the efficacy and safety of medication therapy.

Development of a method for determination of osmotic pump controlled-release tablets of lorcaserin hydrochloride in beagle dog plasma and its application to pharmacokinetic study / 中国药理学通报

Aim To develop an UPLC-MS/MS method to determine the concentration of lorcaserin hydrochloride in beagle plasma, and study the pharmacokinetics of osmotic pump controlled-release tablets of lorcaserin hydrochloride. Methods A randomized crossover design was used, carbamazepine as the internal standard(IS), and plasma protein precipitation with acetonitrile. The chromatographic was Phenomenex Polar C18 column(100 mm×2. 1 mm, 3 μm), and acetonitrile - water(containing 10 mmol·L-1 ammonium acetate and 0.1% formic acid)(40:60, V/V)was mobile phase. Multiple reaction monitoring mode and electrospray positive ionization were used to detect lorcaserin hydrochloride. The MS/MS ion transitions were monitored at m/z 196.2→129.2 for lorcaserin hydrochloride and m/z 237→194.1 for carbamazepine, respectively. Results The linear range was 1 to 500 μg·L-1(r=0.999 2), the extraction recovery rate ranged from 87.70% to 89.70%, the precision RSD was 9.7%. The accuracy and matrix effect met the requirements, and the stability of lorcaserin hydrochloride was good in -20 ℃ refrigerator for 45 d, repeated freezing and thawing for three times, placed at room temperature for 24 h, and the disposed samples placed in automatsampler for 6 h were stable. The main pharmacokinetic parameters of the controlled-release tablet and immediate-release tablet were as follows:Tmax was(8.00±1.27)h and(1.00±0.13)h, Cmax was(70.56±3.73)μg·L-1 and(176.33±16.73)μg·L-1, and AUC0-t was(966.33±7.56)μg·h·L-1 and(973.05±69.09)μg·h·L-1, respectively. Conclusions The established UPLC-MS/MS method can be used to study the pharmacokinetics of lorcaserin hydrochloride in the plasma of beagle dogs, and osmotic pump controlled-release tablets has sustained release effect.

Advance in Traditional Chinese Medicine for Alzheimer's disease by regulating microglia / 中国药理学通报

Microglia, the main immune macrophages in the central nervous system, can be highly involved in the occurrence and development of Alzheimer's disease(AD)through microglia polarization and receptor protein expression. Traditional Chinese Medicine has been demonstrated to have regulatory effects on MG. Many active components in Traditional Chinese herbs play important roles in decreasing β-amyloid peptide(Aβ)accumulation, inhibiting neuro-inflammation and regulating microglia polarization etc. In this study the role of microglia in the pathogenesis of AD and the mechanism by which Traditional Chinese Medicine regulating microglia are reviewed to provide a reference for the treatment of AD.

Interventional treatment and early-stage follow-up of pulmonary atresia with intact ventricular septum / 中华儿科杂志

Objective: To explore the application value of percutaneous peripheral interventional therapy in pulmonary atresia with intact ventricular septal (PA-IVS). Methods: Retrospective case summary. The data was collected from 25 children who were hospitalized at the Children's Hospital,Zhejiang University School of Medicine from August 2019 to August 2022, had been diagnosed with PA-IVS by echocardiography, and underwent interventional treatment. The sex, age, weight, operation time, radiation exposure time, and radiation dose of the patients were collected. The patients were divided into the arterial duct stenting group and the non-stenting group. Preoperative tricuspid annular diameters and Z scores, right ventricular length diameters, and right ventricular/left ventricular length-diameter ratios were compared by paired t-tests. Right ventricular systolic pressure difference, oxygen saturation, lactic acid before and after the surgery were compared for 24 children who received percutaneous balloon pulmonary valvuloplasty. Right ventricular improvement in 25 children after operation was analyzed. The correlation between postoperative oxygen saturation and postoperative right ventricular systolic blood pressure difference, the degree of pulmonary valve opening and the Z value of tricuspid valve ring in the non-stenting group were analyzed. Results: A total of 25 patients with PA-IVS were enrolled in the study, of whom 19 were males and 6 females, with an age at surgery of 12 (6, 28) days and a weight of (3.7±0.5) kg. One of them underwent only stenting of the arterial duct; 20 children underwent only percutaneous pulmonary valve perforation and balloon angioplasty; 4 children underwent both procedures. The Z-value of the tricuspid ring was -1.5±1.2 in the group with arterial duct stenting, and -0.1±0.4 in the group without stenting (t=2.77, P=0.010). The tricuspid regurgitant flow rate 1 month after surgery was significantly lower than the preoperative ((3.4±0.6) vs. (4.8±0.9) m/s, t=6.62,P<0.001). In the 24 children with percutaneous pulmonary valve perforation and balloon angioplasty, the preoperative right ventricular systolic blood pressure was (110±32) mmHg, and the postoperative systolic blood pressure was (52±19) mmHg (1 mmHg=0.133 kPa) (F=59.55, P<0.001). The factors that may affect postoperative oxygen saturation in 20 cases of non-stenting group were analyzed. The results suggested that the pre and post-operative right ventricular systolic blood pressure differences (r=-0.11, P=0.649), and the pulmonary valve orifice opening (r=-0.31, P=0.201) and tricuspid annulus Z value (r=-0.18, P=0.452) at 1 month after the operation were not significantly correlated with the postoperative oxygen saturation. Conclusions: Interventional therapy can be used as the first choice for one-stage operation of PA-IVS. Percutaneous pulmonary valve perforation and balloon angioplasty are more suitable for children with well-developed right ventricles, tricuspid annulus, and pulmonary arteries. While the smaller the tricuspid annulus, the more dependent it is on the ductus arteriosus and thus patients are more suitable for arterial duct stenting.

Effect of Shionone on Neuron Apoptosis After Spinal Cord Injury in Mice / 中国医学科学院学报

Objective To explore the effect of shionone(SHI)on motor function in the mouse model of spinal cord injury(SCI)and probe into the underlying molecular mechanism.Methods C57BL/6 mice were treated to induce the SCI model and then assigned into a model group(SCI group),a SCI+SHI group,and a sham surgery(control)group.The Basso mouse scale(BMS)score was determined to evaluate the recovery of motor function in SCI mice.Hematoxylin-eosin(HE)staining,Nissl staining,and immunofluorescence staining were employed to examine the fibrosis,morphological changes of neurons,and neuron apoptosis in the spinal cord tissue of SCI mice,respectively.The mouse hippocampal neuronal cell line HT22 was cultured in vitro and then classified into tumor necrosis factor α(TNF-α)induction and SHI groups.Western blotting was employed to determine the expression of apoptosis-associated proteins.Network pharmacology,gene ontology annotation,and Kyoto Encyclopedia of Genes and Genomes pathway enrichment were employed to predict the possible molecular targets and signaling pathways of SHI in promoting functional recovery from SCI.Furthermore,the prediction results were verified by in vitro and in vivo experiments.Results Compared with the SCI group,the SCI+SHI group showed increased BMS score on days 21,28,35,and 42(P=0.003,P=0.004,P=0.023,and P=0.007,respectively),reduced area of spinal cord fibrosis(P=0.021),increased neurons survived(P=0.001),and down-regulated expression of cleaved cysteine aspastic acid-specific protease 3(cleaved Caspase-3)(P=0.017).Compared with the TNF-α group,the SHI group presented down-regulated expression levels of cleaved Caspase-3 and Bax(P=0.010,P=0.001)and up-regulated expression level of Bcl-2(P=0.001).The results of bioinformatics analysis showed that SHI might improve the motor function of SCI mice via the phosphatidylinositol 3-kinase(PI3K)/protein kinase B(Akt)signaling pathway.The results of in vivo and in vitro experiments showed that SHI inhibited the phosphorylation of PI3K and Akt in SCI mice or HT22 cells exposed to TNF-α(all P<0.05).The number of apoptotic HT22 cells after treatment with insulin-like growth factor 1 was higher than that in the SHI group(P=0.003).Conclusion SHI may inhibit neuron apoptosis via the PI3K/Akt signaling pathway,thereby promoting the recovery of motor function in SCI mice.