Objective To investigate the roles of glucose-regulated protein 75(GRP75)and voltage-dependent anion channel 1(VDAC1)in heroin-induced arrhythmia.Methods Based on transcriptomic data from primary myocardial cells treated with heroin and the GSE31821 dataset from the Gene Expression Omnibus(GEO),differentially expressed genes(DEGs)were identified using R software.Enrichment analysis of DEGs was performed.The protein-protein interaction(PPI)network was constructed using STRING database,and key genes were selected using Cytoscape.Molecular docking of key genes was performed using HDOCK,followed by in vivo valida-tion.A total of 60 SD rats were randomly divided into control,model,model+7 d,model+14 d,and model+21 d groups.A rat model of heroin addiction was established,and the expression levels of DEGs in myocardial tissue were assessed using immunohistochemical staining and quantitative real-time PCR.Results A total of 51 DEGs primarily enriched in muscle cell development,myofibrils,actin binding,arrhythmic right ventricular cardiomyopathy,calcium signaling,and apoptosis pathways were identified.Based on the PPI and Cytoscape analyses,GRP75 and VDAC1 were identified as key genes.Molecular docking indicated a strong interaction between GRP75 and VDAC1,which form a stable complex.The results of immunohistochemical staining and qRT-PCR showed that the expression levels of GRP75 and VDAC1 were significantly increased in the model group compared to those in the control group(P＜0.05),and their expres-sion increased(P＜0.05)with the intervention period of heroin in a time-dependent manner.Conclusion GRP75 and VDAC1 may con-tribute to heroin-induced arrhythmogenesis.

Objective To investigate the roles of glucose-regulated protein 75(GRP75)and voltage-dependent anion channel 1(VDAC1)in heroin-induced arrhythmia.Methods Based on transcriptomic data from primary myocardial cells treated with heroin and the GSE31821 dataset from the Gene Expression Omnibus(GEO),differentially expressed genes(DEGs)were identified using R software.Enrichment analysis of DEGs was performed.The protein-protein interaction(PPI)network was constructed using STRING database,and key genes were selected using Cytoscape.Molecular docking of key genes was performed using HDOCK,followed by in vivo valida-tion.A total of 60 SD rats were randomly divided into control,model,model+7 d,model+14 d,and model+21 d groups.A rat model of heroin addiction was established,and the expression levels of DEGs in myocardial tissue were assessed using immunohistochemical staining and quantitative real-time PCR.Results A total of 51 DEGs primarily enriched in muscle cell development,myofibrils,actin binding,arrhythmic right ventricular cardiomyopathy,calcium signaling,and apoptosis pathways were identified.Based on the PPI and Cytoscape analyses,GRP75 and VDAC1 were identified as key genes.Molecular docking indicated a strong interaction between GRP75 and VDAC1,which form a stable complex.The results of immunohistochemical staining and qRT-PCR showed that the expression levels of GRP75 and VDAC1 were significantly increased in the model group compared to those in the control group(P＜0.05),and their expres-sion increased(P＜0.05)with the intervention period of heroin in a time-dependent manner.Conclusion GRP75 and VDAC1 may con-tribute to heroin-induced arrhythmogenesis.

Twelve compounds were isolated from Liquidambaris Resina by silica gel column chromatography and thin layer chromatography. Their structures were identified on the basis of spectral data, electron capture detector data, and physicochemical properties as(2'R, 3'R)-2',3'-dihydroxy-hydrocinnamyl-(E)-cinnamate(1),(E)-cinnamyl-(E)-cinnamate(2), cinnamic acid(3), 28-norlup-20(29)-en-3-one-17β-hydroperoxide(4), erythrodiol(5), 13β,28-epoxy-30-hydroxyolean-1-en-3-one(6),(3β)-olean-12-ene-3,23-diol(7), 2α,3α-dihydroxy-olean-12-en-28-oic acid(8), 28-hydroxyolean-12-en-3-one(9), 3-epi-oleanolic acid(10), 3-oxo-oleanolic acid(11), and hederagenin(12). Compound 1 was a new cinnamic acid ester derivative and compounds 2-4,6-8, and 12 were isolated from Liquidambaris Resina for the first time. Compounds 4, 5, 10, and 12 exerted inhibitory effects on the proliferation of human umbilical vein endothelial cells(HUVEC) with the IC_(50) values of(17.43±2.17),(35.32±0.61),(27.50±0.80), and(46.30±0.30) μmol·L~(-1), respectively.
Humans ; Oleanolic Acid ; Endothelial Cells ; Esters ; Cinnamates ; Triterpenes/chemistry* ; Molecular Structure

Objective: To investigate the relationship between body mass index (BMI) and sexual development in Chinese children. Methods: A nationwide multicenter and population-based large cross-sectional study was conducted in 13 provinces, autonomous regions and municipalities of China from January 2017 to December 2018. Data on sex, age, height, weight were collected, BMI was calculated and sexual characteristics were analyzed. The subjects were divided into four groups based on age, including ages 3-<6 years, 6-<10 years, 10-<15 years and 15-<18 years. Multiple Logistic regression models were used for evaluating the associations of BMI with sexual development in children. Dichotomous Logistic regression was used to compare the differences in the distribution of early and non-early puberty among normal weight, overweight and obese groups. Curves were drawn to analyze the relationship between the percentage of early puberty and BMI distribution in girls and boys at different Tanner stages. Results: A total of 208 179 healthy children (96 471 girls and 111 708 boys) were enrolled in this study. The OR values of B2, B3 and B4+ in overweight girls were 1.72 (95%CI: 1.56-1.89), 3.19 (95%CI: 2.86-3.57), 7.14 (95%CI: 6.33-8.05) and in obese girls were 2.05 (95%CI: 1.88-2.24), 4.98 (95%CI: 4.49-5.53), 11.21 (95%CI: 9.98-12.59), respectively; while the OR values of G2, G3, G4+ in overweight boys were 1.27 (95%CI: 1.17-1.38), 1.52 (95%CI: 1.36-1.70), 1.88 (95%CI: 1.66-2.14) and in obese boys were 1.27 (95%CI: 1.17-1.37), 1.59 (95%CI: 1.43-1.78), and 1.93 (95%CI: 1.70-2.18) (compared with normal weight Tanner 1 group,all P<0.01). Analysis in different age groups found that OR values of obese girls at B2 stage and boys at G2 stage were 2.02 (95%CI: 1.06-3.86) and 2.32 (95%CI:1.05-5.12) in preschool children aged 3-<6 years, respectively (both P<0.05). And in the age group of 6-10 years, overweight girls had a 5.45-fold risk and obese girls had a 12.54-fold risk of B3 stage compared to girls with normal BMI. Compared with normal weight children, the risk of early puberty was 2.67 times higher in overweight girls, 3.63 times higher in obese girls, and 1.22 times higher in overweight boys, 1.35 times higher in obese boys (all P<0.01). Among the children at each Tanner stages, the percentage of early puberty increased with the increase of BMI, from 5.7% (80/1 397), 16.1% (48/299), 13.8% (27/195) to 25.7% (198/769), 65.1% (209/321), 65.4% (157/240) in girls aged 8-<9, 10-<11 and 11-<12 years, and 6.6% (34/513), 18.7% (51/273), 21.6% (57/264) to 13.3% (96/722), 46.4% (140/302), 47.5% (105/221) in boys aged 9-<10, 12-<13 and 13-<14 years, respectively. Conclusions: BMI is positively correlated with sexual development in both Chinese boys and girls, and the correlation is stronger in girls. Obesity is a risk factor for precocious puberty in preschool children aged 3-<6 years, and 6-<10 years of age is a high risk period for early development in obese girls.
Adolescent ; Body Mass Index ; Child ; Child, Preschool ; China/epidemiology* ; Cross-Sectional Studies ; Female ; Humans ; Male ; Obesity/epidemiology* ; Overweight/epidemiology* ; Puberty ; Puberty, Precocious ; Sexual Development

Objective: To explore the heterogeneity and correlation of clinical phenotypes and genotypes in children with disorders of sex development (DSD). Methods: A retrospective study of 1 235 patients with clinically proposed DSD in 36 pediatric medical institutions across the country from January 2017 to May 2021. After capturing 277 DSD-related candidate genes, second-generation sequencing was performed to analyzed the heterogeneity and correlation combined with clinical phenotypes. Results: Among 1 235 children with clinically proposed DSD, 980 were males and 255 were females of social gender at the time of initial diagnosis with the age ranged from 1 day of age to 17.92 years. A total of 443 children with pathogenic variants were detected through molecular genetic studies, with a positive detection rate of 35.9%. The most common clinical phenotypes were micropenis (455 cases), hypospadias (321 cases), and cryptorchidism (172 cases) and common mutations detected were in SRD5A2 gene (80 cases), AR gene (53 cases) and CYP21A2 gene (44 cases). Among them, the SRD5A2 mutation is the most common in children with simple micropenis and simple hypospadias, while the AMH mutation is the most common in children with simple cryptorchidism. Conclusions: The SRD5A2 mutation is the most common genetic variant in Chinese children with DSD, and micropenis, cryptorchidism, and hypospadias are the most common clinical phenotypes. Molecular diagnosis can provide clues about the biological basis of DSD, and can also guide clinicians to perform specific clinical examinations. Target sequence capture probes and next-generation sequencing technology can provide effective and economical genetic diagnosis for children with DSD.
3-Oxo-5-alpha-Steroid 4-Dehydrogenase/genetics* ; Child ; China/epidemiology* ; Cryptorchidism/genetics* ; Disorders of Sex Development/genetics* ; Female ; Genital Diseases, Male ; Genotype ; Humans ; Hypospadias/genetics* ; Male ; Membrane Proteins/genetics* ; Penis/abnormalities* ; Phenotype ; Retrospective Studies ; Steroid 21-Hydroxylase/genetics*

Hepatotoxicity is a common side effect for patients treated with gefitinib, but the related pathogenesis is unclear and lacks effective predictor and management strategies. A multi-omics approach integrating pharmacometabolomics, pharmacokinetics and pharmacogenomics was employed in non-small cell lung cancer patients to identify the effective predictor for gefitinib-induced hepatotoxicity and explore optional therapy substitution. Here, we found that patients with rs4946935 AA, located in Forkhead Box O3 (FOXO3) which is a well-known autophagic regulator, had a higher risk of hepatotoxicity than those with the GA or GG variant (OR = 18.020, 95%CI = 2.473 to 459.1784, P = 0.018) in a gefitinib-concentration dependent pattern. Furthermore, functional experiments identified that rs4946935_A impaired the expression of FOXO3 by inhibiting the promotor activity, increasing the threshold of autophagy initiation and inhibiting the autophagic activity which contributed to gefitinib-induced liver injury. In contrast, erlotinib-induced liver injury was independent on the variant and expression levels of FOXO3. This study reveals that FOXO3 mutation, leading to autophagic imbalance, plays important role in gefitinib-induced hepatotoxicity, especially for patients with high concentration of gefitinib. In conclusion, FOXO3 mutation is an effective predictor and erlotinib might be an appropriately and well-tolerated treatment option for patients carrying rs4946935 AA.

Objective: To explore the promotion effect of laparoscopic standardized surgery for gastric cancer observational in some regional medical centers in Shanghai. Methods: A retrospective cohort study was carried out. Eleven regional medical centers in Shanghai received the promotion program of laparoscopic standardized surgery for gastric cancer, which was led by Ruijin Hospital, Shanghai Jiaotong University School of Medicine (Shanghai Minimally Invasive Surgery Center) from January to December 2020. Clinicopathological data of gastric cancer patients treated at these 11 regional medical centers before and after the promotion program were collected. Inclusion criteria were as follows: patients undergoing laparoscopic distal gastrectomy or total gastrectomy; gastric cancer confirmed by pathology; without distant metastasis or peritoneal metastasis. Patients who did not undergo laparoscopic D2 radical resection, or received neoadjuvant chemotherapy before surgery, or without complete clinical data were excluded. Patients undergoing laparoscopic surgery from January to December 2019 were included in the pre-promotion group (46 cases). Patients undergoing laparoscopic surgery from January to December 2021 were included in the post-promotion group (102 cases). In addition, patients undergoing laparoscopic surgery at Ruijin Hospital from January 2021 to December were included in the control group (138 cases). The baseline data, perioperative measurements postoperative complications, and pathological results of the three groups were analyzed and compared. Results: There were no significant differences in baseline characteristics among the three groups (all P>0.05). Compared with the pre-promotion group, the operation time in post-promotion group was significantly shorter [(207.3±36.0) minutes vs. (254.2±47.1) minutes, t=7.038,P<0.001], and the number of harvested lymph node was significantly more (24.4±12.2 vs. 18.9±5.5, t=2.900, P=0.004). However, there were no significant differences in the extent of resection, time to fluid intake, and postoperative hospital stay between the two groups (all P>0.05). Compared with the control group, the operation time [(207.3±36.0) minutes vs (172.6±26.0) minutes, t=8.281, P<0.001], time to fluid intake [(6.3±3.2) days than (5.5±3.0) days, t=2.029, P=0.044], and the postoperative hospital stay [(14.3±5.6) days vs. (10.1±4.8) days, t=6.036, P<0.001] in the post- promotion group were still longer. Total gastrectomy was less common in the post-promotion group compared with the control group [18 cases (17.6%) vs. 41 cases (29.7%), χ²=7.380, P=0.007]. However, there was no significant difference in the number of harvested lymph node between the two groups (P>0.05). The morbidity of postoperative complication in the post-promotion group (9.8%, 10/102) was significantly lower than that in the pre-promotion group (23.9%, 11/46) (χ²=5.183, P=0.023), while above morbidity was not significantly different between the post-promotion group and the control group [9.8% vs. 6.5% (9/138), χ²=0.867, P=0.352]. Conclusion: After the promotion of laparoscopic standardized surgery for gastric cancer in regional medical centers, the standardization degree of surgery has been improved, and the morbidity of postoperative complication decreases. Laparoscopic standardized surgery for gastric cancer can be promoted to more regional medical centers.
China ; Gastrectomy/methods* ; Hospitals ; Humans ; Laparoscopy ; Lymph Node Excision/methods* ; Postoperative Complications/etiology* ; Retrospective Studies ; Stomach Neoplasms/pathology* ; Treatment Outcome

With the aging process of population in the society, the prevalence of cardiovascular diseases (CVD) in China is increasing continuously and the number of dental patients with CVD is increasing gradually too. Due to the lack of guidelines for dental patients with CVD in our country, how to implement standardized preoperative evaluation and perioperative risk prevention remains a problem to be solved for dentists at present. The present expert consensus was reached by combining the clinical experiences of the expert group of the Fifth General Dentistry Special Committee, Chinese Stomatological Association and respiratory and cardiology experts in diagnosis and treatment for CVD patients, and by systematically summarizing the relevant international guidelines and literature regarding the relationship between CVD and oral diseases and the diagnosis and treatment of dental patients with heart failure, hypertension and antithrombotic therapy. The consensus aims to provide, for the dental clinicians, the criteria on diagnosis and treatment of CVD in dental patients in China so as to reduce the risk and complications, and finally to improve the treatment levels of dental patients with CVD in China.
Cardiovascular Diseases/prevention & control* ; China/epidemiology* ; Consensus ; Dental Care ; Humans ; Oral Medicine

Objective:To investigate the effects of solute carrier family 39 (SLC39) A14 on proliferation, migration and invasion of diffuse large B-cell lymphoma (DLBCL) OCI-LY3 cells.Methods:The human DLBCL cell line OCI-LY3 was divided into Vector group (transfected with empty control plasmid) and SLC39A14 group (transfected with SLC39A14 plasmid). The proliferation of OCI-LY3 cells in the two groups was detected by CCK-8 method, the migration and invasion of cells were detected by Transwell method, and the expression level of SLC39A14 protein and the expressions of PI3K-AKT-mTOR signaling pathway-related proteins in OCI-LY3 cells were detected by Western blotting.Results:Compared with the Vector group, the cell proliferation ability in the SLC39A14 group was increased from day 3 to day 5 (all P < 0.05).The results of Transwell cell migration assay showed that the number of migrating cells after 36 h in the Vector group was (64±4) cells, and that in the SLC39A14 group was (236±25) cells. The cell migration ability in the SLC39A14 group was increased, and the difference was statistically significant ( t = 15.02, P < 0.05). The results of Transwell cell invasion assay showed that the number of invasive cells in the Vector group was (32±2) cells, and that in the SLC39A14 group was (127±17) cells. The cell invasion ability in the SLC39A14 group was increased, and the difference was statistically significant ( t = 8.33, P < 0.05).The results of Western blotting showed that the expression levels of pmTOR, pAKT and pPI3K proteins in the SLC39A14 group were all increased. Conclusions:SLC39A14 may be involved in the occurrence and development of DLBCL through PI3K-AKT-mTOR signaling pathway.

Objective:To investigate the variation trend of peripheral blood CD34 + cells during the hematopoietic stem cell mobilization and its influence on the collection timing and results. Methods:The clinical data of 62 patients with hematologic diseases undergoing autologous peripheral blood hematopoietic stem cell mobilization from April 2012 to March 2017 in Shanxi Provincial Cancer Hospital were analyzed. Mobilization regimen used chemotherapy combined with granulocyte colony-stimulating factor (G-CSF) to monitor the number of white blood cells (WBC), mononuclear cells (MNC), CD34 + cells in peripheral blood and apheresis concentrates, and the correlation with CD34 + cells was analyzed. Furthermore, the receiver operating characteristic (ROC) curve was used to establish the threshold to start apheresis. Results:MNC (5.66±1.11)×10 8/kg and CD34 + cell count (2.15±1.20)×10 6/kg were obtained in 62 patients who received 136 times collection in total. The peak of peripheral blood CD34 + cells count appeared at day 4-5 after the treatment of G-CSF, and then it went down. CD34 + cell count in the product was correlated with the peripheral blood CD34 + cell count collected on the day ( r = 0.879, P < 0.01), and it was also correlated with the peripheral blood WBC and MNC collected on the day as well as MNC count in the product (all P < 0.05). Furthermore, the ROC curve analysis demonstrated that peripheral blood CD34 + cells count > 23/μl was the optimal threshold for stem cell collection on the day, 85.2% of patients reaching up to the threshold could be successfully collected at one time. Conclusions:The variation trend of peripheral blood CD34 + cell count can guide the best time of stem cell collection in clinic. Peripheral blood CD34 + cell count is the reliable index to predict CD34 + cells count in the products. Peripheral blood CD34 + cells count > 23/μl could be used as the collection threshold.