1.The Relationship of Transcription Factor BRF1 Expression to Tumor and Cardiomyopathy
Li-Ling ZHENG ; Yong-Luan LIN ; Mei-Ling CHEN ; Zheng-Yan ZHONG ; Shuping ZHONG
Progress in Biochemistry and Biophysics 2025;52(9):2241-2251
TFIIB-related factor 1 (BRF1) is an important transcription factor. It specifically regulates the transcription of RNA polymerase III-dependent genes (RNA Pol III genes). The products of these genes are some small non-coding RNAs, including transfer RNAs (tRNAs) and 5S ribosomal RNAs (5S rRNA). The transcription levels of tRNAs and 5S rRNA vary with changes in intracellular BRF1 amounts. tRNAs and 5S rRNA play a crucial role in determining protein synthesis. Studies have demonstrated that dysregulation of tRNAs and 5S rRNA is closely related to cell growth, proliferation, transformation, and even tumorigenesis. BRF1 is a key factor determining the generation of tRNAs and 5S rRNA. Increasing BRF1 expression enhances cell proliferation and transformation, promoting tumor development. In contrast, repressing BRF1 activity decreases the rates of cell proliferation and transformation, and inhibits tumor growth. High levels of BRF1 are found in the samples of patients suffering from hepatocellular carcinoma, breast cancer, gastric carcinoma, lung cancer, prostate carcinoma, and other cancers. It indicates that high levels of BRF1 are closely related to the occurrence of human cancer and may be a common landmark of tumors. But there is discrepancy in the regulatory mechanisms and signaling pathways of BRF1 overexpression in different cancers. In general, high levels of BRF1 in patients suffering from cancer show short survival period and poor prognosis. However, there is one exception, namely breast cancer. Approximate 80% of cases of breast cancer are estrogen receptor-positive (ER+) and 20% are ER-. The cases with high levels of BRF1 reveal longer survival period and better prognosis after they accepted the hormone treatment by Tamoxifen (Tam), compared to the cases with low level BRF1. It seems like a contradiction. Most of the cases with high levels of BRF1 belong to ER+ status. Tam has been used to treat ER+ cases of breast cancer after diagnosis and surgery. Thus, hormone therapy, such as Tam, is more effective on these patients. This is because, on one hand, that Tam competes with E2 (17β-estradiol) to bind to estrogen receptor α (ERα), but does not dissociate to occupy the receptors, blocking E2 binding to this receptor and inhibiting its biological effects. On other hand, Tam can inhibit the expression of BRF1, leading to a decline of intracellular BRF1 levels. Therefore, the actual levels of BRF1 are lower in the patients with ER+ breast cancer. It appears the prognosis of the high BRF1 expression cases better than that of the low BRF1 expression cases. Myocardial hypertrophy manifests magnification of cardiomyocyte volume rather than number increasing in the postnatal heart. Myocardial hypertrophy is a critical risk factor underlying cardiovascular diseases. No matter how myocardial hypertrophy occur, it will ultimately lead to myocardial dysfunction and heart failure. Hypertrophic growth of cardiomyocytes requires a large amount of protein synthesis to meet its needs of cardiomyocyte growth. Animal models and cell experiments have shown that myocardial hypertrophy stimulates a significant increase in BRF1 expression and transcription of tRNAs and 5S rRNA. Interestingly, elevated levels of BRF1 are found in the myocardium tissues of patients with myocardial hypertrophy. These studies demonstrate that BRF1 indeed plays a critical role in myocardial hypertrophy. In summary, high levels of BRF1 are found in patients suffering from different cancers and myocardial hypertrophy. It implies that BRF1 is a promising biological target of cancer and cardiomyopathy. BRF1 is expected to become a common biomarker for early diagnosis and prognostic observation of different human cancers. It is also an important biomarker for the diagnosis and treatment of cardiomyopathy. BRF1 not only holds an important position in the field of basic medical research but also has great prospects for translational medicine. In the present article, we summarize the progress on studies of BRF1 expressions in cancer and cardiomyopathy, proposes future research directions. It is a new research area. Here, we emphasize the significancy of BRF overexpression in the two huge diseases of human, cancer and cardiomyopathy to raise people's attention to this field.
2.Water quality of self-provided wells water in Haidian District in Beijing in 2018 - 2022
Yongmei HU ; Xueying LIU ; Shuping ZHU ; Haiping CHEN
Journal of Public Health and Preventive Medicine 2024;35(3):86-89
Objective To investigate the water quality and sanitary conditions of rural self-provided wells water in Haidian District, Beijing, and to provide reference for strengthening water supply management of self-provided wells. Methods The water quality monitoring data of rural self-provided wells in Haidian District from 2018 to 2022 were analyzed. Results A total of 1 568 water samples were tested in 2018-2022 , of which 1 486 were qualified, with a qualified rate of 94.77%. The qualified rate in each year was 86.75% , 92.86% , 97.48% , 98.06% , and 99.34% , respectively , and the difference was statistically significant ( χ2= 75.296 , P<0.05). The qualified rates of sensory traits and general chemical indexes, toxicological indexes and microbial indexes were 97.70%, 97.58% and 98.28%, respectively. There were statistically significant differences in the qualified rates among the three indexes in 2018, 2019 and 2021 (P < 0.05). The unqualified indicators included total hardness, total number of colonies, total coliform, fluoride, nitrate and turbidity, with a qualified rate of 97.96%, 98.41%, 99.17%, 99.11%, 98.47% and 99.94%, respectively. Conclusion The water quality of self-provided wells in rural Haidian District is good. Relevant departments should continue to strengthen the supervision of self-provided wells, such as the supervision of self-provided wells disinfection devices and water treatment equipment, to ensure the safety of drinking water for residents.
3.Application value of renal artery resistance index in the diagnosis of intra-abdominal hypertension in critically ill patients
Baoquan CHEN ; Ming CHEN ; Jinyang XU ; Guorong LYU ; Yanfen YANG ; Shuping YANG
Chinese Journal of Emergency Medicine 2024;33(3):360-364
Objective:To explore the application value of renal artery resistance index in the diagnosist of intra-abdominal hypertension (IAH) in critically ill patients.Methods:89 patients with risk factors of IAH in the intensive care unit of Zhangzhou Hospital Affiliated to Fujian Medical University from February 2022 to June 2022 were retrospective analyzed. The intra-abdominal pressure (IAP) were measured by bladder, and patients divided into IAH group (IAP≥12 mmHg) and non-IAH group (IAP <12 mmHg). The resistance index (RI) of the right renal aorta, segment artery and interlobar artery were measured by color Doppler ultrasound. The difference between the measurement indicators of patients in the IAH and non-IAH groups and the correlation with IAP were analyzed. As for different indicators to predict the diagnostic efficacy of IAH, ROC curve analysis was used to evaluate the effect. And further multivariate logistic regression analysis was to find independent risk predictor.Results:A total of 89 patients were included in the study, including 44 patients with normal IAP and 45 patients diagnosed IAH. There were significant differences in the right renal aorta, segmental artery and interlobar artery RI (all P<0.01). The interlobar artery RI≥0.698 was the highest diagnostic cut-off,area under the curve was 0.914, sensitivity was 82.2%, specificity was 97.7%, and Jordon index was 0.799. The Spearman correlation analysis of IAP and the ultrasonographic measurements revealed a strong correlation between right renal interlobar artery RI and IAP ( r=0.741, P<0.01). The multivariate logistic regression analysis showed that the right renal interlobar artery RI ( OR= 24.472, 95% CI:5.122~116.919, P<0.01) was an independent risk predictor of IAH ( P<0.01). Conclusion:Right renal interlobar artery RI had better diagnostic efficacy of IAH,renal ultrasound could be used as an alternative, non-invasive technique for the diagnosis and follow-up of IAH.
4.Effect mechanism of Gualou guizhi granule on neurological function and synaptic plasticity in rats with cerebral ischemia-reperfusion injury
Wenting CHEN ; Shiyi CHEN ; Yanan LI ; Yi FENG ; Shuping LUO ; Yuqin ZHANG
China Pharmacy 2024;35(16):1951-1956
OBJECTIVE To investigate the effect mechanism of Gualou guizhi granule on neurological function and synaptic plasticity in rats with cerebral ischemia-reperfusion injury. METHODS The rats were randomly divided into sham operation group, model group and Gualou guizhi granule group (3.6 g/kg), with 6 rats in each group. The cerebral ischemia-reperfusion injury model was established by the suture occlusion method. Two hours after modeling, the model rats were given relevant medicine or normal saline intragastrically, once a day, for 7 consecutive days. After the last medication, the neurological function of rats was evaluated [calculated by modified neurological severity scores (mNSS) and corner turning percentage]; the neuronal apoptosis rate of brain histiocyte in the ischemic side of rats was detected in each group; the positive expressions of growth associated protein 43 (GAP43) and microtubule associated protein 2 (MAP2) were detected; protein expressions of neuron-specific nuclear protein (NeuN), synaptophysin-1 (Syn-1), postsynaptic density protein-95 (PSD-95), peroxisome proliferators-activated receptor γ (PPARγ), brain-derived neurotrophic factor (BDNF) and tropomyosin receptor kinase B (TrkB), as well as mRNA expressions of NeuN, Syn-1 and PSD-95 were detected. RESULTS Compared with the model group, mNSS, corner turning percentage and neuronal apoptotic rate were decreased significantly in Gualou guizhi granule group (P<0.01); GAP43 represented weak immunoreactivity, and MAP2 represented moderate immunoreactivity; protein expressions of NeuN, Syn-1, PSD-95, PPARγ, BDNF, TrkB and mRNA expressions of Syn-1, NeuN, PSD-95 were all increased significantly (P<0.05 or P<0.01). CONCLUSIONS Gualou guizhi granule can promote synaptic plasticity by activating BDNF/TrkB signaling pathway, thus playing a protective role in cerebral ischemia-reperfusion injury in rats.
5.Clinical features and genetic analysis of early-onset spinocerebellar ataxia type 5 caused by de novoSPTBN2 gene mutation
Guangjin LUO ; Shuping TANG ; Jiashan LI ; Yang LI ; Chong WANG ; Leihong ZHANG ; Jun CHEN ; Aiyun YUAN ; Mei HOU ; Dianrong SUN
Chinese Journal of Neurology 2024;57(6):607-615
Objective:To summarize the clinical and genetic characteristics of early-onset spinocerebellar ataxia type 5 (SCA5) caused by SPTBN2 gene mutation. Methods:The clinical and genetic data of a child with early-onset SCA5 diagnosed in the Department of Children′s Rehabilitation, Women and Children′s Hospital Affiliated to Qingdao University in February 2022 were retrospectively analyzed. The literatures related to early-onset SCA5 in major databases at home and abroad were retrieved and summarized.Results:The patient, a 4 years and 1 month old girl, was admitted to hospital because of "unable to stand independently at 2 years and 3 months", primarily presented with developmental delay, ataxia, hypotonia, and tendon hyperreflexia during infancy. Progressive cerebellar atrophy was observed on brain magnetic resonance imaging. A de novo heterozygous mutation of the SPTBN2 c.793G>C(p.Asp265His) was identified in the patient. Following hospitalization, the child received comprehensive rehabilitation therapy encompassing physical, occupational, language, educational interventions as well as bicycle ergometer training and transcranial magnetic stimulation. The patient was followed-up for more than 1 year to 4 years and 1 month old, whose motor function, cognitive abilities, and language skills were improved to some extent. A total of 13 English articles and 1 Chinese article were retrieved from the databases. A total of 20 early-onset SCA5 patients have been reported, with onset ages all within 12 months. Infants exhibited decreased muscle tone and delayed motor milestones, with the main clinical manifestations of ataxia, generalized developmental delay, and cerebellar atrophy. The previously reported cases involved 11 mutation sites in the SPTBN2 gene, and the main types of mutations were de novo missense mutations. The mutation site in this case has not been reported in the previous literature. Conclusions:Early-onset SCA5 is a rare autosomal dominant disorder caused by heterozygous mutations in the SPTBN2 gene. The main clinical manifestations include ataxia from infancy, developmental retardation and cerebellar atrophy. Early rehabilitation intervention can improve the degree of the dysfunction.
6.Ten years of practice in the operation and quality control of the first human milk bank in East China
Wenjuan CHEN ; Xiaohui CHEN ; Xue CHU ; Beibei LIU ; Yanjie CHEN ; Xiaoshan HU ; Xiangyun YAN ; Shuping HAN
Chinese Journal of Perinatal Medicine 2024;27(7):536-543
Objective:To conduct a phased summary and analysis of the operation and quality control (QC) of the first human milk bank (HMB) in East China over a ten-year period.Methods:Data on the operation of the HMB at Women's Hospital of Nanjing Medical University, characteristics of donors and recipients, clinical application of donated milk, and operational costs from August 1, 2013, to July 31, 2023, were collected, organized, analyzed, and described. Quality and safety management of the HMB began in 2016, with QC measures implemented. Chi-square tests were used to compare data related to the operation of the HMB, donors, and recipient infants before QC (2013-2015) and after QC (2016-2023). Results:Over the ten-year period since its establishment, the HMB received donor human milk (DHM) from 1 974 donors, totaling 9 390.41 liters. The qualification rate of donors was 86.47% (1 707/1 974), with a qualification rate of DHM of 98.01% (9 203.21/9 390.41) and 21 757 donation instances, with the highest individual donation count reaching 195 times. In the past 10 years, due to the epidemic of the new coronavirus in 2020, the number of milk donors, the amount of DHM and the total number of milk donations decreased significantly, but the amount of DHM per capita and the number of milk donations per capita showed a continuous upward trend. Compared to the period before QC, the qualification rate of donors [96.75% (1 253/1 295) vs. 66.86% (454/679), χ 2=340.33, P<0.001] and the qualification rate of DHM [98.19% (8 366.76/8 521.08) vs. 96.22% (836.45/869.33), χ 2=16.33, P<0.001] both improved after QC. A total of 11 197 recipients received 6 615.38 liters of DHM, with a utilization rate of 71.88% (6 615.38/9 203.21). The current operation mode of the HMB is "voluntary donation, free use". Over ten years, the costs for consumables, testing, labor, energy, and fixed assets amounted to 9.36 million CNY, with an operational cost of 996.32 CNY per liter (9.36 million/9 390.41 L) and approximately 1.00 CNY per milliliter of DHM. Conclusions:The hospital's HMB has been operating stably for ten years, and abundant DHM benefits many newborns. QC measures have effectively increased the qualification rates of both donors and DHM, providing better nutritional support for the treatment of critically ill infants. However, the operational costs of the HMB are relatively high, necessitating the exploration of an operational model suitable for China's national conditions.
7.Advances in breast milk metabolomics research
Yanjie CHEN ; Wenjuan CHEN ; Xiangyun YAN ; Shushu LI ; Xiaohui CHEN ; Shuping HAN
Chinese Journal of Perinatal Medicine 2024;27(7):562-565
Breast milk is an ideal source of nutrition for the growth and development of infants. The study of metabolomics integrates holistic and dynamic technological approaches, which offers practical feasibility for the analysis of small molecular metabolites in breast milk, including their composition, structure, functionality, as well as their relationship with maternal and infant health. This article provides an overview of the origins and development of breast milk metabolomics, influencing factors, and the relationship between breast milk metabolites and the health of the offsprings.
8.Effect of individual exercise training as the core cardiac rehabilitation program on the rehabilitation of patients with coronary heart disease after percutaneous coronary intervention
Shuping GE ; Wei CHEN ; Xinxin JIA ; Min GAO ; Min HE ; Cunyu QIN
The Journal of Practical Medicine 2024;40(18):2607-2611
Objective To investigate the effect of individual exercise training on the rehabilitation of patients with coronary heart disease(CHD)after percutaneous coronary intervention(PCI).Methods A total of 81 patients between January 2021 and December 2023 were randomly allocated into an observation group(n=41)and a control group(n=40)using a simple random number Tab.method.The control group received routine post-operative rehabilitation intervention,while the observation group received individualized exercise training as the core component of cardiac rehabilitation intervention.The study compared the effects of rehabilitation,cardiac function parameters[left ventricular ejection fraction(LVEF),left ventricular end-diastolic diameter(LVEDD)],exercise endurance measures[6-minute walking distance(6MWD)],and quality of life assessed by Seattle Angina Pecina Scale(SAQ)scores between the two groups before and after a three-month intervention period.Results The total recovery response rate in the observation group was higher than that in the control group(P<0.05).LVEF,LVEDD,6 MWD,maximum exercise load and SAQ scales(P>0.05),LVEF were higher than before intervention(t=3.345,2.480,3.165,5.016,2.059,4.582,4.443,3.353,P<0.05),and LVEDD was lower than before intervention(t=3.335,P<0.05).Conclusion The individualized exercise training-based cardiac rehabili-tation program demonstrates potential for enhancing cardiac function and exercise endurance in patients with CHD following PCI,thereby improving their overall quality of life.This finding holds significant clinical implications.
9.Tildrakizumab for moderate-to-severe plaque psoriasis in Chinese patients: A 12-week randomized placebo-controlled phase III trial with long-term extension
Chen YU ; Songmei GENG ; Bin YANG ; Yunhua DENG ; Fuqiu LI ; Xiaojing KANG ; Mingye BI ; Furen ZHANG ; Yi ZHAO ; Weili PAN ; Zhongwei TIAN ; Jinhua XU ; Zhenghua ZHANG ; Nan YU ; Xinsuo DUAN ; Shuping GUO ; Qing SUN ; Weiquan LI ; Juan TAO ; Zhijun LIU ; Yuanyuan YIN ; Gang WANG
Chinese Medical Journal 2024;137(10):1190-1198
Background::There is a need for effective and safe therapies for psoriasis that provide sustained benefits. The aim of this study was to assess the efficacy and safety of tildrakizumab, an anti-interleukin-23p19 monoclonal antibody, for treating moderate-to-severe plaque psoriasis in Chinese patients.Methods::In this multi-center, double-blind, phase III trial, patients with moderate-to-severe plaque psoriasis were enrolled and randomly assigned (1:1) to receive subcutaneous tildrakizumab 100 mg or placebo at weeks 0 and 4. Patients initially assigned to placebo were switched to receive tildrakizumab at weeks 12, 16, and every 12 weeks thereafter. Patients in the tildrakizumab group continued with tildrakizumab at week 16, and every 12 weeks until week 52. The primary endpoint was the Psoriasis Area and Severity Index (PASI 75) response rate at week 12.Results::At week 12, tildrakizumab demonstrated significantly higher PASI 75 response rates (66.4% [73/110] vs. 12.7% [14/110]; difference, 51.4% [95% confidence interval (CI), 40.72, 62.13]; P <0.001) and Physician’s Global Assessment (60.9% [67/110] vs. 10.0% [11/110]; difference, 49.1% [95% CI, 38.64, 59.62]; P <0.001) compared to placebo. PASI 75 response continued to improve over time in both tildrakizumab and placebo-switching to tildrakizumab groups, reaching maximal efficacy after 28 weeks (86.8% [92/106] vs. 82.4% [89/108]) and maintained up to 52 weeks (91.3% [95/104] vs. 87.4% [90/103]). Most treatment-emergent adverse events were mild and not related to tildrakizumab. Conclusion::Tildrakizumab demonstrated durable efficacy through week 52 and was well tolerated in Chinese patients with moderate-to-severe plaque psoriasis.Trial registration::ClinicalTrials.gov, NCT05108766.
10.Clinical effects of parallel combined flow-through perforator flaps in the treatment of circular hot crush injuries in limbs with blood supply disorder
Shuping ZHOU ; Shimin LI ; Yingguang SHI ; Liwu ZHENG ; Chaonan CHANG ; Junjie CHEN ; Huanpeng WANG ; Ke SUN ; Xiuhuan WANG ; Linbo LIU
Chinese Journal of Burns 2024;40(7):665-672
Objective:To explore the clinical effects of parallel combined flow-through perforator flaps in the treatment of circular hot crush injuries in limbs with blood supply disorder.Methods:The study was a retrospective observational study. From April 2016 to December 2022, 4 cases with circular hot crush injuries in limbs with blood supply disorder were admitted to the Department of Burns and Plastic Surgery of the 988 th Hospital of Joint Logistics Support Force of PLA, including 3 males and 1 female, aged from 24 to 48 years. Among them, 2 cases were injured in the calf and 2 cases were injured in the forearm. After emergency debridement, the area of skin and soft tissue defects was from 20 cm×20 cm to 44 cm×20 cm. The patients had defects in tibialis anterior and posterior tibial arteries with a length of 13 to 18 cm, and in ulnar and radial arteries with a length of 9 to 12 cm. Flaps were designed and cut, including a flow-through anterolateral thigh perforator flap with area of 20 cm×9 cm to 24 cm×21 cm carrying the descending branch of the lateral circumflex femoral artery and the accompanying veins of 8 to 18 cm in length; and a flow-through posterior tibial artery perforator flap with area of 21 cm×13 cm and 20 cm×14 cm carrying the posterior tibial artery, the accompanying veins with a length of 14 and 17 cm respectively, and the great saphenous vein with a length of 22 and 21 cm. The circular hot crush injury wounds in the calf with blood supply disorder were repaired by a parallel combination of flow-through posterior tibial artery perforator flap and flow-through anterolateral thigh perforator flap, and the circular hot crush injury wounds in the forearm with blood supply disorder were repaired by a parallel combination of bilateral flow-through anterolateral thigh perforator flap, and the injured main vessels were reconstructed. The donor site wounds of flap were closed directly or treated with split-thickness skin grafts from abdomen. After surgery, the blood supply and survival of the flap and distal affected limb, the healing of wounds in the donor and recipient sites, the survival of the skin graft in the flap donor site were observed. During follow-up, the condition of flaps, the appearance, blood supply, and function of affected limbs were observed. At the last follow-up, the foot and ankle functions were evaluated according to the scoring standards of American Orthopedic Foot and Ankle Association, and the wrist and hand function was evaluated according to the trial standard of replantation of amputated upper limb function assessment of the Hand Surgery of Chinese Medical Association. Results:The flaps and distal affected limbs of 4 patients had good blood circulation and successfully survived after surgery. The wounds of 3 cases successfully healed, while one patient with circular hot crush injury in the forearm experienced exudation in the recipient site in the later stage, and the wound healed after re-expansion and suturing. The donor site wounds healed smoothly, and the skin grafts successfully survived. During follow-up of 12 to 24 months after surgery, the flaps were slightly swollen, the limbs had good appearance, normal blood circulation, and fine functional recovery. At the last follow-up, the foot and ankle function of 2 patients with circular hot crush injuries in the calf was evaluated as good in 1 case and commonly in 1 case; the wrist and hand function of 2 patients with circular hot crush injuries in the forearm was evaluated as excellent in 1 case and good in 1 case.Conclusions:The parallel combined flow-through perforator flap can reconstruct the damaged main blood vessels and repair the wound at the same time. It can not only effectively save the limb, but also restore part of the function of the affected limb. It is one of the effective methods to treat the circular hot crush injuries in limbs with blood supply disorder.


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