Cardiac myosin binding protein-C(cMyBP-C),as an important component of myocardium coarse filaments,can regulate cross-bridge circulation through phosphorylation or dephosphorylation and participates in myocardial systolic and diastolic functions.cMyBP-C plays an important role in the occurrence and development of cardiovascular diseases(CVDs)such as acute myocardial infarction,cardiomyopathy,heart failure,aortic stenosis,hypertensive myocardial hypertrophy,and myocarditis,but the specific mechanism has not been fully clarified.This article reviews the research progress on the role of cMyBP-C in CVDs,in order to provide references for the diagnosis,treatment and prognosis evaluation of CVDs.

Objective To explore the effect of LIMK1 on the progression of cervical cancer(CC).Methods HeLa and C-33A human cervical cancer cells overexpressing LIMK1 were established and injected subcutaneously into nude mice.The tumor volume was measured and expression of NOX2,NOX4,p-Src,p-RUNX3,RUNX3,and MMP-9 proteins in tumor cells was detected by Western blot assays.LIMK1-overexpressing HeLa and C-33A cells were cultured in 5％O2 with antioxidants.The protein expression of LIMK1,NOX4,p-Src,p-RUNX3,RUNX3 and MMP-9 in the cells was detected by Western blot assays.Cell migration was assessed by a scratch assay.Transwell assays were used to assess cell migration and invasion.A monoclonal proliferation assay was used to assess cell proliferation.Results The tumor volume in nude mice injected with LIMK1-overexpressing HeLa cells was increased significantly,and NOX2,NOX4,p-Src,p-RUNX3 and MMP-9 protein levels were increased,while RUNX3 protein expression was decreased.In LIMK1-overexpressing HeLa and C-33A cells,the protein expression of LIMK1,NOX4,p-Src,p-RUNX3,and MMP-9 was increased,RUNX3 protein expression was decreased,and cell migration,invasion,and proliferation were increased.However,after adding antioxidants,the expression levels of NOX4,p-Src,p-RUNX3,RUNX3 and MMP-9 proteins,and cell migration,invasion,and proliferation were not different from those of control cells.Conclusions LIMK1 promotes the progression of cervical cancer by enhancing the ROS/Src pathway,thereby promoting the migration,invasion,and proliferation of cervical cancer cells.

Objective:To investigate the current situation of key endemic disease prevention and control in Shanxi Province, and provide a scientific basis for further strengthening the implementation of prevention and control measures.Methods:In 2021, monitoring of key endemic disease prevention and control projects in Shanxi Province was carried out in accordance with the current national monitoring plans for iodine deficiency disorders and water source high iodine areas, for endemic fluorosis, endemic arsenic poisoning, Kashin-Beck disease, and Keshan disease. The effect of prevention and control measures was evaluated in accordance with the "Evaluation Measures for Key Endemic Disease Control and Elimination (2019 Edition)". Patient management services and treatment subsidy projects were carried out in accordance with the "Management Service Standards for Endemic Disease Patients" and the "Management Measures for Treatment of Endemic Disease Patients".Results:All 117 counties (cities, districts, hereinafter referred to as counties) in Shanxi Province had reached the national elimination standards for iodine deficiency disorders, and the overall iodine nutrition of the population was generally suitable. However, the consumption rate of qualified iodine salt in 8 counties was ≤90%, and the iodine nutrition of pregnant women in 13 counties was insufficient. The water improvement rate in 295 villages in 12 counties across the province with high water iodine level was 80.68% (238/295), and the proportion of villages with qualified water iodine after water improvement was 38.31% (113/295). The prevention and control measures of 93.55% (58/62) of the counties in the province with endemic fluorosis caused through drinking water reached the national control standards. Totally 20 counties ravaged by coal-burning borne endemic fluorosis, 16 counties ravaged by drinking water borne endemic arsenicosis (high arsenic areas), 35 counties ravaged by Kashin-Beck disease, and 11 counties ravaged by Keshan disease met the national elimination standards. In 2021, 11 197 patients with endemic diseases were followed up and managed in Shanxi Province, and drug treatment programs were carried out on 3 413 patients with skeletal fluorosis, 2 088 patients with Kashin-Beck disease, and 10 patients with chronic Keshan disease.Conclusions:The overall prevention and control of key endemic diseases in Shanxi Province remains under control or elimination. However, the water improvement in some drinking water borne endemic fluorosis areas still needs to be further strengthened. Measures for water improvement and supply of non-iodized salt in water source high iodine areas still need to be coordinated and promoted. Key endemic disease patients in Shanxi Province have basically achieved standardized management.

The hazards of water-borne iodine excess is a relatively serious public health problem in China. The government has made great progress in prevention and controlling of the hazards of water-borne iodine excess through measures such as supplying non-iodized salt and implementing measures such as improving water quality to decrease iodine. However, there is a lack of corresponding evaluation criteria for measuring the implementation level and effectiveness of prevention and control measures, which urgently needs to be addressed. This article explores the technical indicators for establishing control standards for water source high iodine hazards in China through a review and analysis of relevant laws and regulations, normative documents, standards, and research progress in the field of high iodine prevention and control at home and abroad. It is recommended that administrative villages be used as units to evaluate the control status of water source high iodine hazards; after water improvement and iodine reduction, the iodine content of residents' drinking water should be ≤100 μg/L; meanwhile, the median urinary iodine for school-age children should be between 100 and < 300 μg/L, thyroid enlargement rate should be less than 5%.

Metformin is currently a strong candidate anti-tumor agent in multiple cancers. However, its anti-tumor effectiveness varies among different cancers or subpopulations, potentially due to tumor heterogeneity. It thus remains unclear which hepatocellular carcinoma (HCC) patient subpopulation(s) can benefit from metformin treatment. Here, through a genome-wide CRISPR-Cas9-based knockout screen, we find that DOCK1 levels determine the anti-tumor effects of metformin and that DOCK1 is a synthetic lethal target of metformin in HCC. Mechanistically, metformin promotes DOCK1 phosphorylation, which activates RAC1 to facilitate cell survival, leading to metformin resistance. The DOCK1-selective inhibitor, TBOPP, potentiates anti-tumor activity by metformin in vitro in liver cancer cell lines and patient-derived HCC organoids, and in vivo in xenografted liver cancer cells and immunocompetent mouse liver cancer models. Notably, metformin improves overall survival of HCC patients with low DOCK1 levels but not among patients with high DOCK1 expression. This study shows that metformin effectiveness depends on DOCK1 levels and that combining metformin with DOCK1 inhibition may provide a promising personalized therapeutic strategy for metformin-resistant HCC patients.
Animals ; Antineoplastic Agents/therapeutic use* ; Carcinoma, Hepatocellular/metabolism* ; Cell Line, Tumor ; Clustered Regularly Interspaced Short Palindromic Repeats ; Genome ; Humans ; Liver Neoplasms/metabolism* ; Metformin/therapeutic use* ; Mice ; Phosphorylation ; Synthetic Lethal Mutations ; Transcription Factors/metabolism* ; rac GTP-Binding Proteins/metabolism*

Objective:To learn about the status of iodine deficiency disorders (IDD) and iodine nutrition of residents in Shanxi Province since the implementation of the standard of "Iodine Content in Edible Salt" (GB 26878-2011), to evaluate the level of prevention and control of IDD, and to provide scientific basis for adjusting prevention and control strategies.Methods:The data of core indicators monitored by Shanxi Province in accordance with the requirements of the national iodized salt and IDD monitoring program for each year from 2012 to 2021 were comprehensively reviewed, and the change trends of the indicators such as coverage rate of iodized salt, consumption rate of qualified iodized salt, children's median urinary iodine and goiter rate, and pregnant women's median urinary iodine were analyzed; the evaluation of IDD elimination in counties (cities and districts, hereinafter referred to as counties) was analyzed.Results:From 2012 to 2021, the coverage rate of iodized salt in Shanxi Province was remained > 95%; from 2012 to 2014 (transition period between new and old standard iodized salt), the consumption rate of qualified iodized salt had an upward trend (χ 2trend = 2 703.32, P < 0.001), with a downward trend from 2015 to 2017 (before and after the reform of the salt industry system, χ 2trend = 122.18, P < 0.001), and with an upward trend from 2018 to 2021 (after the reform of the salt industry system, χ 2trend = 455.11, P < 0.001), from 2018, the consumption rate of qualified iodized salt remained > 90%; from 2015 to 2021, the average content of salt iodine was between 23 - 25 mg/kg, and the coefficient of variation of salt iodine was 15% - 18%. From 2014 to 2021, the median urinary iodine of children in Shanxi Province remained at 200 - 250 μg/L, the median urinary iodine of pregnant women remained at 150 - 200 μg/L, and the goiter rate of children remained below 5%. Every year, iodine nutrition of pregnant women in some counties was insufficient. In 2016, the proportion of counties with insufficient iodine nutrition of pregnant women was high, reached 30.0% (12/40); from 2018 to 2021, the proportion of counties with insufficient iodine nutrition of pregnant women had a downward trend (χ 2trend = 9.37, P = 0.002), which was 11.1% (13/117) in 2021. In 2020, 117 counties in the province reached the IDD elimination standard, with a compliance rate of 100.0%. Conclusions:Since the implementation of the current salt iodine content standard for 10 years, the consumption rate of qualified iodized salt has gradually stabilized and remained at a high level, which can ensure that IDD is in a sustainable state of elimination in Shanxi Province, and the iodine nutrition of school-age children and pregnant women is generally at a suitable level. However, there are a certain number of counties with insufficient iodine nutrition of pregnant women. It is recommended to guide pregnant women to supplement iodine or set the average standard of salt iodine for pregnant women separately.

Objective:To verify Baveno VI criteria, Expanded-Baveno VI criteria, liver stiffness×spleen diameter-to-platelet ratio risk score (LSPS), and platelet count/spleen diameter ratio (PSR) in evaluating the severity value of esophageal varices (EV) in patients with non-cirrhotic portal hypertension (NCPH).Methods:111 cases of NCPH and 204 cases of hepatitis B cirrhosis who met the diagnostic criteria were included in the study. NCPH included 70 cases of idiopathic non-cirrhotic portal hypertension (INCPH) and 41 cases of nontumoral portal vein thrombosis (PVT). According to the severity of EV on endoscopy, they were divided into the low-bleeding-risk group (no/mild EV) and the high-bleeding-risk group (moderate/severe EV). The diagnostic value of Baveno VI and Expanded-Baveno VI criteria was verified to evaluate the value of LSPS and PSR for EV bleeding risk severity in NCPH patients. The t-test or Mann-Whitney U test was used to compare the measurement data between groups. Comparisons between counting data groups were performed using either the χ2 test or the Fisher exact probability method. Results:Considering endoscopy was the gold standard for diagnosis, the missed diagnosis rates of low/high bleeding risk EVs in INCPH/PVT patients with Baveno VI and Expanded-Baveno VI criteria were 50.0%/30.0% and 53.8%/50.0%, respectively. There were no statistically significant differences in platelet count (PLT), spleen diameter, liver stiffness (LSM), LSPS, and PSR between low-bleeding-risk and high-bleeding-risk groups in INCPH patients, and the area under the receiver operating characteristic curve (AUC) of LSPS and PSR was 0.564 and 0.592, respectively ( P=0.372 and 0.202, respectively). There were statistically significant differences in PLT, spleen diameter, LSPS, and PSR between the low and high-bleeding risk groups in PVT patients, and the AUCs of LSPS and PSR were 0.796 and 0.833 ( P=0.003 and 0.001, respectively). In patients with hepatitis B cirrhosis, the Baveno VI and Expanded-Baveno VI criteria were used to verify the low bleeding risk EV, and the missed diagnosis rates were 0 and 5.4%, respectively. There were statistically significant differences in PLT, spleen diameter, LSM, LSPS and PSR between the low-bleeding-risk and high-bleeding-risk groups ( P<0.001). LSPS and PSR AUC were 0.867 and 0.789, respectively ( P<0.05). Conclusion:Baveno VI and Expanded-Baveno VI criteria have a high missed diagnosis rate for EVs with low bleeding risk in patients with INPCH and PVT, while LSPS and PSR have certain value in evaluating EV bleeding risk in PVT patients, which requires further clinical research.

Endemic disease prevention and control is a great livelihood project. The three-year campaign of endemic disease prevention and control is a concrete embodiment of the idea of "people-centered", and an important measure to help the disease areas get rid of poverty and build a well-off society in an all-round way. Since the founding of the People's Republic of China, Shanxi Province has made great achievements in the prevention and control of endemic disease. At this stage, Shanxi Province has strengthened the organization and management, and the six major actions have been carried out simultaneously, and the goal of comprehensive control and elimination of key endemic disease has been achieved steadily. In this paper, the situation of tackling key problems in Shanxi Province is introduced, and the establishment and improvement of sustainable elimination and control mechanism of endemic disease are prospected.

Objective To investigate the mechanism of TNF-related apoptosis-inducing ligand (TRAIL) promoting apoptosis of pancreatic cancer cells SW1990, Patu8988 and BxPC3. Methods Three kinds of pancreatic cancer cells SW1990, Patu8988 and BxPC3 were transfected with the pCA13 plasmid carrying TRAIL gene ( pCA13 TRAIL group) and the blank plasmid control ( pCA13 group) , respectively. The expression of TRAIL mRNA in transfected cells was detected by RT-PCR, and the expression of TRAIL protein was detected by Western blot. The apoptosis rate and expression of TRAIL receptor R1 and R2 were detected by flow cytometry. Apoptosis was detected by TUNEL and Hoechst double staining, and observed by electron microscopy. The expression of caspase-3 in transfected cells was detected by immunohistochemistry. Results SW1990, Patu8988 and BxPC3 cells can expresse TRAIL mRNA and protein within 24 h after transfection. The apoptotic rate at 24 h after transfection was (27. 30 ± 5. 14)％, (13. 52 ± 0. 95)％ and (31. 40 ± 8. 70)％,respectively, which was higher than that of pCA13 group [(10. 58 ± 1. 88)％,(8. 42 ± 0. 46)％ and (16.11 ±1.66)％], respectively. The expression rates of TRAIL-R1 were (61.37 ± 3.05)％,(42.10 ± 5. 11)％ and (36. 64 ± 4. 84)％, respectively, and the expression rates of TRAIL-R2 were (36. 20 ± 4. 83)％,(37. 26 ± 8. 46)％ and (24. 32 ± 3. 71)％, respectively,which were higher than those of pCA13 group except PATU8988 cells. Positivity rates of caspase-3 were ( 14. 64 ± 5. 35 )％, ( 9. 92 ± 5. 50 )％ and (16. 12 ± 6. 74)％, which were obviously higher than ( 3. 01 ± 1. 50 )％, ( 1. 75 ± 0. 50 )％ and ( 3. 79 ± 1. 58)％ in pCA13 group,and the differences were statistically significant(P<0. 05). Conclusions TRAIL could up-regulate the expression of TRAIL R1 and R2 in multiple pancreatic cancer cell lines in vitro, and thus promote cell apoptosis.

Objective To test the value of miRNA-30c(miR-30c)in early diagnosis of gastric cancer. Methods Serum miR-30c expression levels were detected by using quantitative real-time polymerase chain reaction in 80 patients with advanced gastric cancer, 35 patients with early stage gastric cancer and 35 healthy controls in the Affiliated People's Hospital of Inner Mongolia Medical University from August 2014 to August 2017. The receiver operating characteristic (ROC) curves and the area under the curve (AUC) were analyzed to test the efficacy of the miR-30c in distinguishing advanced gastric cancer, early stage gastric cancer and healthy controls. Results The expression level of serum miR-30c in advanced gastric cancer (0.45±0.11) was lower than that in early stage gastric cancer (0.54±0.15) (t = 5.2, P < 0.05). Compared with the healthy controls (0.61±0.12), miR-30c was down-expressed in the serum of early stage gastric cancer patients(t=6.7,P<0.05).Compared with the traditional tumor markers,the AUC of miR-30c was the biggest (0.92±0.03) in early stage and advanced gastric cancer groups, and the sensitivity and specificity in the diagnosis of gastric cancer were 90 % and 84 %, respectively. The AUC of miR-30c was 0.87±0.04 in early stage gastric cancer and healthy controls, and the sensitivity and specificity in the diagnosis of gastric cancer were 70 % and 86 %, respectively. Conclusion miR-30c might be used as a potential serum biomarker for the early diagnosis of gastric cancer.