1.Oncogenic β-catenin-driven liver cancer is susceptible to methotrexate-mediated disruption of nucleotide synthesis
Fangming LIU ; Yuting WU ; Baohui ZHANG ; Shuhui YANG ; Kezhuo SHANG ; Jie LI ; Pengju ZHANG ; Weiwei DENG ; Linlin CHEN ; Liang ZHENG ; Xiaochen GAI ; Hongbing ZHANG
Chinese Medical Journal 2024;137(2):181-189
Background::Liver cancer is largely resistant to chemotherapy. This study aimed to identify the effective chemotherapeutics for β-catenin-activated liver cancer which is caused by gain-of-function mutation of catenin beta 1 ( CTNNB1), the most frequently altered proto-oncogene in hepatic neoplasms. Methods::Constitutive β-catenin-activated mouse embryonic fibroblasts (MEFs) were established by deleting exon 3 ( β-cateninΔ(ex3)/+ ), the most common mutation site in CTNNB1 gene. A screening of 12 widely used chemotherapy drugs was conducted for the ones that selectively inhibited β-cateninΔ(ex3)/+ but not for wild-type MEFs. Untargeted metabolomics was carried out to examine the alterations of metabolites in nucleotide synthesis. The efficacy and selectivity of methotrexate (MTX) on β-catenin-activated human liver cancer cells were determined in vitro. Immuno-deficient nude mice subcutaneously inoculated with β-catenin wild-type or mutant liver cancer cells and hepatitis B virus ( HBV); β-cateninlox(ex3)/+ mice were used, respectively, to evaluate the efficacy of MTX in the treatment of β-catenin mutant liver cancer. Results::MTX was identified and validated as a preferential agent against the proliferation and tumor formation of β-catenin-activated cells. Boosted nucleotide synthesis was the major metabolic aberration in β-catenin-active cells, and this alteration was also the target of MTX. Moreover, MTX abrogated hepatocarcinogenesis of HBV; β-cateninlox(ex3)/+ mice, which stimulated concurrent Ctnnb1-activated mutation and HBV infection in liver cancer. Conclusion::MTX is a promising chemotherapeutic agent for β-catenin hyperactive liver cancer. Since repurposing MTX has the advantages of lower risk, shorter timelines, and less investment in drug discovery and development, a clinical trial is warranted to test its efficacy in the treatment of β-catenin mutant liver cancer.
2.Clinical and experimental research progress of Wumei Pills in the treatment of digestive system diseases
Na REN ; Xiuzhen HAN ; Weiwei LIU ; Yan LI ; Shuihong LI ; Hongtao SHANG
International Journal of Traditional Chinese Medicine 2024;46(8):1102-1105
Wumei Pills is mostly used to treat ulcerative colitis, irritable bowel syndrome, intestinal polyps, chronic atrophic gastritis, gastroesophageal reflux disease, gastric cancer and other digestive system diseases with its modified formula or combination with Western medicine. Wumei Pills can play a role in treating digestive system diseases through antioxidant stress, Inhibiting inflammatory response, regulating intestinal flora, anti-tumor, promoting intestinal mucosal repair, etc. Most of the related research on the mechanism of Wumei Pills in the treatment of digestive system diseases were studied in a single pathway. The relationship between other mechanisms and pathways is worthy of further exploration. In addition, the current research mostly focuses on the lower digestive system diseases with diarrhea as the main manifestation, and there is still room for research and reporting in the treatment of upper digestive system diseases.
3.pH/Temperature Responsive Curcumin-Loaded Micelle Nanoparticles Promote Functional Repair after Spinal Cord Injury in Rats via Modulation of Inflammation
Taibao QIAN ; Zhixiang LI ; Lijun SHANG ; Sutao HUANG ; Guanglin LI ; Weiwei ZHENG ; Yingji MAO
Tissue Engineering and Regenerative Medicine 2023;20(6):879-892
BACKGROUND:
The formation of an inhibitory inflammatory microenvironment after spinal cord injury (SCI) remains a great challenge for nerve regeneration. The poor local microenvironment exacerbates nerve cell death; therefore, the reconstruction of a favorable microenvironment through small-molecule drugs is a promising strategy for promoting nerve regeneration.
METHODS:
In the present study, we synthesized curcumin-loaded micelle nanoparticles (Cur-NPs) to increase curcumin bioavailability and analyzed the physical and chemical properties of Cur-NPs by characterization experiments. We established an in vivo SCI model in rats and examined the ability of hind limb motor recovery using Basso–Beattie– Bresnahan scoring and hind limb trajectory assays. We also analyzed neural regeneration after SCI using immunofluorescence staining.
RESULTS:
The nanoparticles achieved the intelligent responsive release of curcumin while improving curcumin bioavailability. Most importantly, the released curcumin attenuated local inflammation by modulating the polarization of macrophages from an M1 pro-inflammatory phenotype to an M2 anti-inflammatory phenotype. M2-type macrophages can promote cell differentiation, proliferation, matrix secretion, and reorganization by secreting or expressing pro-repair cytokines to reduce the inflammatory response. The enhanced inflammatory microenvironment supported neuronal regeneration, nerve remyelination, and reduced scar formation. These effects facilitated functional repair in rats, mainly in the form of improved hindlimb movements.
CONCLUSION
Here, we synthesized pH/temperature dual-sensitive Cur-NPs. While improving the bioavailability of the drug, they were also able to achieve a smart responsive release in the inflammatory microenvironment that develops after SCI. The Cur-NPs promoted the regeneration and functional recovery of nerves after SCI through anti-inflammatory effects, providing a promising strategy for the repair of SCIs.
4.Analyzing the distribution characteristics of occupational pneumoconiosis in Sichuan Province, 2012-2021
Enfei JIANG ; Li LIN ; Weiwei SHANG ; Lili DU
China Occupational Medicine 2023;50(2):205-208
5.Integrated database-based Screening Cohort for Asian Nomadic descendants in China (Scan-China): Insights on prospective ethnicity-focused cancer screening
Yuelin YU ; Liying QIAO ; Jing HAN ; Weiwei WANG ; Weiwei KANG ; Yunjing ZHANG ; Shu SHANG ; Ruogu MENG ; Lin ZHUO ; Siyan ZHAN ; Yunfeng XI ; Shengfeng WANG
Epidemiology and Health 2023;45(1):e2023048-
Established in 2017, the Screening Cohort for Asian Nomadic descendants in China (Scan-China) has benefited over 180,000 members of a multi-ethnic population, particularly individuals of Mongolian descent compared with the general population (Han ethnicity), in the Inner Mongolia Autonomous Region, China. This cohort study aims to evaluate the effectiveness of cancer screening and serve as a real-world data platform for cancer studies. The 6 most prevalent cancers in China are considered—namely, breast, lung, colorectal, gastric, liver and esophageal cancer. After baseline cancer risk assessments and screening tests, both active and passive follow-up (based on the healthcare insurance database, cancer registry, the front page of hospital medical records, and death certificates) will be conducted to trace participants’ onset and progression of cancers and other prevalent chronic diseases. Scan-China has preliminarily found a disproportionately lower screening participation rate and higher incidence/mortality rates of esophageal and breast cancer among the Mongolian population than among their Han counterparts. Further research will explore the cancer burden, natural history, treatment patterns, and risk factors of the target cancers.
6.Summary of the best evidence for adult aerosol inhalation nursing practice
Xi QU ; Weiwei SHANG ; Wanting HU ; Ping ZHANG
Chinese Journal of Modern Nursing 2021;27(20):2697-2702
Objective:To search, evaluate and integrate the best evidence of adult aerosol inhalation nursing practice, and to provide basis for the establishment of adult aerosol inhalation nursing practice standard.Methods:The evidence-based nursing method was applied to retrieve relevant literatures from domestic and foreign databases and related websites according to the "6S" model, and the retrieval time was from the establishment of the database to October 10, 2020. The Johns Hopkins evidence grading system was used to grade the evidence. Appraisal of Guidelines for Research and Evaluation Instrument Ⅱ (AGREEⅡ) (2017 edition) and literature quality evaluation standards and evidence recommendation system (2014 edition) of Australian JBI Evidence-based Health Care Center were used to evaluate the quality of various studies and the level of evidence recommendation.Results:A total of 16 literatures were included, including 4 guidelines, 1 systematic evaluation, 7 expert consensus, 1 recommended practice and 3 evidence summaries. The best evidence included 6 aspects, including general principles, choice of tools, implementation process management, adverse events management, aerosol inhalation management for special patients and infection control, with a total of 32 pieces of evidence.Conclusions:This study summarizes the current best evidence on adult aerosol inhalation nursing practice, which can provide evidence-based basis for standardizing the practice of aerosol inhalation by nursing staff, guarantee the standard of patient treatment and improve the quality of care.
7.Case report of congenital complete heart block in premature twins and literatures review
Xiaojing HE ; Zhenzhen LI ; Jipeng SHI ; Yinli CAO ; Weiwei WANG ; Guimei SANG ; Hongxu GUO ; Yun SHANG ; Chenghe TANG
Chinese Journal of Applied Clinical Pediatrics 2020;35(14):1098-1101
Objective:To investigate the pathogenesis, precaution and treatment of neonatal congenital complete heart block (CCHB) in twins.Methods:The clinical data of a case of premature twins with neonatal CCHB from the Department of Neonatology, the First Affiliated Hospital of Xinxiang Medical University were retrospectively analyzed and related literature was reviewed.Results:(1)Case review: the 37-year-old gravida had no symptoms.Fetal ultrasound cardiogram(fUCG)at 23 weeks of gestation indicated bradycardia and CCHB.Then, the mother was diagnosed with undifferentiated connective tissue disease.After treatment with human immunoglobulin, dexamethasone and hydroxychloroquine, fUCG at 31 weeks of gestation still suggested CCHB.An emergency cesarean section was performed on the diagnosis of threatened preterm labor.With weakly positive neonatal antinuclear antibody (ANA), and positive Ro60 and Ro52 autoantibodies, twins were diagnosed with CCHB by 24 hour-Holter monitors.One of the twins was discharged with CCHB (ventricular rate of 80-90 times/min) after systemic therapy, but the weight increased to 2 200 g. The other one of the twins suffered from the sudden decrease of heart rate and blood pressure and finally died of sudden cardiac arrest.(2) Literature search: two cases in Chinese and 9 cases in English were reviewed.Among them, 9 cases were sjogren syndrome type A (SSA)/Ro and sjogren syndrome type B(SSB)/La related CCHB, and 2 cases were idiopathic CCHB.Conclusions:The placental transfer of anti-SSA or anti-SSB is an important mechanism of neonatal CCHB in twins, and other factors may also be involved.Current treatments are unsatisfactory.Most patients need pacemaker implantation.Early diagnosis and prenatal management can improve the prognosis.
8. Analysis on occupational hazards monitoring and occupational health examination in a province
Hui TA ; Jie YANG ; Yingqiong CAO ; Yajia LAN ; Weiwei SHANG
Chinese Journal of Industrial Hygiene and Occupational Diseases 2019;37(7):521-524
Objective:
To find out the status of the monitoring of production environment and physical condition of occupational victims in Sichuan in recent 5 years.
Methods:
Data of health supervision of workers with toxic and harmful activity and occupational health examination in Sichuan Province during 2012-2016, monitoring of occupational harmful factors in Sichuan Province during 2014-2016 were collected from the Network direct reporting system. Descriptive analysis was conducted to analyze the result in May 2017.
Results:
The detection rate of suspected occupational diseases in 23964 enterprises was 1.79% (13392/748291) . The exceeding standard rate of dust, noise, xenobiotic were 32.58% (5089/15622) , 20.28% (4897/24152) and 4.80% (1016/21145) respectively. In addition, state-owned enterprises, state-owned enterprises and collective enterprises showed the highest over-standard rate of dust, noise and exogenous chemical poisons, with the over-standard rate of 69.93% (828/1184) , 29.08% (608/2091) and 11.80% (42/356) respectively. The exceeding rate of dust, noise and exogenous chemical poisons was 32.76% (740/2259) , 28.72% (444/1546) and 7.39% (114/1543) , respectively. Most of the enterprises with higher over-standard rate of dust and chemical poisons are located in Suining City, Panzhihua City, Guangyuan City and Ziyang City.
Conclusion
The focus of occupational hazards in Sichuan is dust and noise, followed by benzene.
9. Analysis of The Quality of Pneumoconiosis Network Direct Report in Sichuan during 2006-2016
Lin HE ; Hui TA ; Yingqiong CAO ; Hongxiu LIAO ; Yajia LAN ; Weiwei SHANG
Chinese Journal of Industrial Hygiene and Occupational Diseases 2018;36(7):506-508
Objective:
To evaluate the quality of Pneumoconiosis Network Direct Report in Sichuan Province in 2006-2016.
Methods:
download all the pneumoconiosis report cards from the Network Direct Report system. Screen out cards based on the diagnosis time that is between January 1st 2006 and December 31st 2016. Using R 3.4.0 software to analysis the number of missing or repeated cards, time-logical error rates, timeliness, reporting year, reporting intervals to evaluate the quality of Pneumoconiosis Network Direct Report and location distribution.
Results:
there are 38 855 pieces of Pneumoconiosis report card in total in 2006-2016. 352 pieces of cards were reported twice. 224 cards were missing. 229 cards have time-logical error. The rate of timely reporting for 2006-2016 years was 66.41% (2 5453/38 326) , 67.14% (24 658/36 726) for new cases, 58.87% (783/1 330) for promoting cases and 4.44% (12/270) for deaths. 87.38% (33 490/38 326) patients was reported in the same year. 10 days was needed to finish one report, confirming-filling cost much more time than filling-report (9.865/49.019) .
Conclusion
the records of pneumoconiosis report cards are much more complete, logical errors are less, and the timeliness was a little bit higher than the average level in China. But it also should be improved. The death cases are difficult to report. It takes longer to diagnose and fill in cards. Improving the timeliness rate can significantly improve the quality of network direct reporting.
10.Practical application of improved lateral radiography of the hip joint
Lei XUE ; Xu SHANG ; Zhuo LIU ; Xiangke DU ; Hao LIANG ; Weiwei QI
Journal of Practical Radiology 2017;33(9):1443-1446
Objective To design a simple and easy to operate new position radiography as same effect as the ordinary lateral position of the hip joint.Methods Using different angles for bone model radiography, the tilt angle of X-ray and the bone model were measured in order to obtain that the femoral head and neck was fully displayed.30 subjects with hip joint disease underwent routine and improved lateral radiography of the hip joint were enrolled, and the actual operations and image quality of the two methods were compared.Results The tilt angle of X-ray was 35°-45°,and the tilt angle of the bone model was 60°-70°, and the score was 3.The new lateral radiography of the hip joint was feasible,the display rate of the articular surface and joint space were 96.7%,the display rate of the femoral head and neck all were 100%,the display rate of the greater trochanter of femur was 80%,the display rate of the lesser trochanter was 100%.Conclusion The improved method of hip joint lateral position of X-ray can better show the femoral head, neck and the rest of the bone.

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