1.Research progress of lysine specific demethylase 1(LSD1)inhibitors
Xiaomeng ZHANG ; Jinyang FU ; Yanan HE ; Jianhong GONG ; Kun DU ; Ya WU ; Yanle ZHI
Journal of China Pharmaceutical University 2024;55(5):685-696
Lysine specific demethylase1(LSD1)is a flavin adenine dinucleotide(FAD)-dependent monoamine oxidase.Studies have confirmed that aberrant expression of LSD1 is closely related to tumor metastasis and proliferation,and is currently one of the important targets for tumor-targeted therapy.In addition,LSD1 is involved in the development of various conditions such as neurodegenerative diseases,cardiovascular diseases,and inflammatory responses.Currently,several inhibitors have been developed for the clinical research stage.In this paper,the structure and mechanism of action of LSD1 and the research progress of LSD1 inhibitors are briefly introduced to provide some reference for the design and development of novel LSD1 inhibitors.
2.Clinical characteristics of children with severe SARS-CoV-2 infection in Yunnan
Yin LI ; Xiaozhong HU ; Congyun LIU ; Xingping TAO ; Rui WANG ; Rui LU ; Yang LI ; Yan PU ; Canrong MU ; Jianhong XU ; Hongmin FU
Chinese Journal of Pediatrics 2024;62(5):451-456
Objective:To investigate the clinical characteristics of 130 children with severe SARS-CoV-2 infection in Yunnan province after the relaxation of non-pharmaceutical interventions, and analyze the risk factors for mortality.Methods:This study is a retrospective case summary that analyzed the demographic data, underlying diseases, clinical diagnoses, disease outcomes, and laboratory results of 130 children with severe COVID-19 infections admitted to nine top-tier hospitals in Yunnan Province from December 2022 to March 2023. According to the prognosis, the patients were divided into survival group and death group. The clinical and laboratory data between the two groups were compared, and the risk factors of death were evaluated. The χ2 test and Mann-Whitney U test were employed to compare between groups, while Spearman correlation test and multiple Logistic regression were used to analyze the risk factors for death. The predictive value of independent risk factors was evaluated by receiver operating characteristic curve. Results:The 130 severe patients included 80 males and 50 females with an onset age of 28.0 (4.5, 79.5) months. There were 97 cases in the survival group and 33 cases in the death group with no significant differences in gender and age between the two groups ( P>0.05). Twenty-five cases (19.2%) out of the 130 patients had underlying diseases, and the number with underlying diseases was significantly higher in death group than in survival group (36.4% (12/33) vs. 13.4%(13/97), χ2=8.36, P=0.004). The vaccination rate in the survival group was significantly higher than that in the death group (86.1% (31/36) vs. 7/17, χ2=9.38, P=0.002). A total of 42 cases (32.3%) of the 130 patients were detected to be infected with other pathogens, but there was no significant difference in the incidence of co-infection between the death group and the survival group (39.3%(13/33) vs. 29.9% (29/97), χ2=1.02, P>0.05). Among the 130 cases, severe respiratory cases were the most common 66 cases (50.8%), followed by neurological severe illnesses 34 cases (26.2%) and circulatory severe 13 cases (10%). Compared to the survival group, patients in the death group had a significantly higher levels of neutrophil, ferritin, procalcitonin, alanine aminotransferase, lactate dehydrogenase, creatine kinase isoenzyme, B-type natriuretic peptide, interleukin-6 and 10 (6.7 (4.0, 14.0) vs. 3.0 (1.6, 7.0)×10 9/L, 479 (298, 594) vs. 268 (124, 424) μg/L, 4.8 (1.7, 10.6) vs. 2.0 (1.1, 3.1) μg/L, 66 (20, 258) vs. 23 (15, 49) U/L, 464 (311, 815) vs. 304 (252, 388) g/L, 71(52, 110) vs. 24(15, 48) U/L, 484 (160, 804) vs. 154 (26, 440) ng/L, 43 (23, 102) vs. 19 (13, 27) ng/L, 216 (114, 318) vs. 86 (45, 128) ng/L, Z=-4.21, -3.67, -3.76, -3.31, -3.75, -5.74, -3.55, -4.65, -5.86, all P<0.05). The correlated indexes were performed by multivariate Logistic regression and the results showed that vaccination was a protective factor from death in severe cases ( OR=0.01, 95% CI 0-0.97, P=0.049) while pediatric sequential organ failure assessment (PSOFA) ( OR=3.31, 95% CI 1.47-7.47, P=0.004), neutrophil-to-lymphocyte ratio (NLR) ( OR=1.56, 95% CI 1.05-2.32, P=0.029) and D dimer ( OR=1.49, 95% CI 1.00-1.02, P=0.033) were independent risk factors for death (all P<0.05). The area under the curve of the three independent risk factors for predicting death were 0.86 (95% CI 0.79-0.94), 0.89 (95% CI 0.84-0.95) and 0.87 (95% CI 0.80-0.94), all P<0.001, and the cut-off values were 4.50, 3.66 and 4.69 mg/L, respectively. Conclusions:Severe SARS-CoV-2 infection can occur in children of all ages, primarily affecting the respiratory system, but can also infect the nervous system, circulatory system or other systems. Children who died had more severe inflammation, tissue damage and coagulation disorders. The elevations of PSOFA, NLR and D dimer were independent risk factors for death in severe children.
3.The impact of short-course total neoadjuvant therapy, long-course chemoradiotherapy, and upfront surgery on the technical difficulty of total mesorectal excision: an observational study with an intraoperative perspective
Cheryl Xi-Zi CHONG ; Frederick H. KOH ; Hui-Lin TAN ; Sharmini Su SIVARAJAH ; Jia-Lin NG ; Leonard Ming-Li HO ; Darius Kang-Lie AW ; Wen-Hsin KOO ; Shuting HAN ; Si-Lin KOO ; Connie Siew-Poh YIP ; Fu-Qiang WANG ; Fung-Joon FOO ; Winson Jianhong TAN
Annals of Coloproctology 2024;40(5):451-458
Purpose:
Total neoadjuvant therapy (TNT) is becoming the standard of care for locally advanced rectal cancer. However, surgery is deferred for months after completion, which may lead to fibrosis and increased surgical difficulty. The aim of this study was to assess whether TNT (TNT-RAPIDO) is associated with increased difficulty of total mesorectal excision (TME) compared with long-course chemoradiotherapy (LCRT) and upfront surgery.
Methods:
Twelve laparoscopic videos of low anterior resection with TME for rectal cancer were prospectively collected from January 2020 to October 2021, with 4 videos in each arm. Seven colorectal surgeons assessed the videos independently, graded the difficulty of TME using a visual analog scale and attempted to identify which category the videos belonged to.
Results:
The median age was 67 years, and 10 patients were male. The median interval to surgery from radiotherapy was 13 weeks in the LCRT group and 24 weeks in the TNT-RAPIDO group. There was no significant difference in the visual analog scale for difficulty in TME between the 3 groups (LCRT, 3.2; TNT-RAPIDO, 4.6; upfront, 4.1; P=0.12). A subgroup analysis showed similar difficulty between groups (LCRT 3.2 vs. TNT-RAPIDO 4.6, P=0.05; TNT-RAPIDO 4.6 vs. upfront 4.1, P=0.54). During video assessments, surgeons correctly identified the prior treatment modality in 42% of the cases. TNT-RAPIDO videos had the highest recognition rate (71%), significantly outperforming both LCRT (29%) and upfront surgery (25%, P=0.01).
Conclusion
TNT does not appear to increase the surgical difficulty of TME.
4.Effects and mechanism of veratramine on the proliferation of human glioblastoma U251 cells
Zizhen CAO ; Lin ZHANG ; Ruoqiu FU ; Yibo ZHAO ; Xiang CHEN ; Jianhong CHEN
China Pharmacy 2023;34(22):2734-2739
OBJECTIVE To explore the effects and potential mechanism of veratramine (VTM) on the proliferation of human glioblastoma U251 cells. METHODS The network pharmacology methods were adopted to screen the targets of ferroptosis related to the effects of VTM on glioblastoma, and to conduct gene ontology and Kyoto Encyclopedia of Genes and Genosomes enrichment analysis. Using U251 cells as the object, CCK-8 assay, the observation of cell morphological changes, DCFH-DA fluorescence probe method, FerroOrange fluorescence probe method and Western blot assay were used to validate the inhibitory effects of VTM on U251 cell proliferation and its possible mechanism. RESULTS Totally 462 targets of ferroptosis related to the effects of VTM on glioblastoma were screened out; they mainly enriched in biological processes such as oxidative stress and apoptosis, and cellular components such as cytoplasmic vesicles and mitochondrial membranes; they affected molecular functions such as iron ion (Fe2+) binding and DNA transcription processes, as well as iron death and phosphoinositide 3-kinase/protein kinase B signaling pathways. VTM with 40, 60, 80, 100, 120 and 140 μmol/L could significantly reduce the cell survival rate (P< 0.01); VTM with 40, 80 and 120 μmol/L could cause cell atrophy and nuclear fragmentation, significantly inhibit the clone formation, increase the levels of intracellular reactive oxygen species (ROS) and Fe2+ levels, increase the expressions of nuclear factor-erythroid 2-related factor 2 (Nrf2) and heme oxygenase 1 (HO-1) protein to different extents, while down-regulate the expression of glutathione peroxidase 4 (GPX4) protein (P<0.05 or P<0.01). CONCLUSIONS VTM can inhibit the proliferation of U251 cells, and promote the accumulation of intracellular ROS and Fe2+, thus inducing ferroptosis; its mechanism might be related to the regulation of the Nrf2/HO-1/GPX4 signaling pathway.
5.The impact of chronic comorbidity in elderly people on relatives’ physical and mental health during the nursing home confinement:A multiple mediator analysis
Hailu ZHU ; Jiaxuan FU ; Yuqing DU ; Yijing HOU ; Yajing LI ; Feng LIU ; Yong YU ; Jianhong WANG ; Zhaozhao HUI ; Mingxu WANG
Journal of Xi'an Jiaotong University(Medical Sciences) 2023;44(4):614-620
【Objective】 To explore the relationship between chronic comorbidity and the physical and mental health of relatives of elderly people during the nursing home confinement, and to analyze the mediating effects of perceived stress and intolerance of uncertainty in this context. 【Methods】 A total of 568 family members of elderly people in nine elderly institutions in Shaanxi Province were selected. The survey included the short version of the Perceived Stress Scale, Intolerance of Uncertainty Scale, and The World Health Organization-5 Well-being Index. The data were analyzed with Stata for correlation and mediation effects. 【Results】 ① The comorbidities of chronic diseases was positively correlated with the perceived stress (r=0.16, P<0.001) and intolerance of uncertainty (r=0.11, P=0.006) of the family members, but negatively correlated with the physical and mental health of the family members (r=-0.13, P=0.002). ② The mediating effect of perceived stress between chronic disease co-morbidity and physical and mental health of family members in older adults was -0.023, accounting for 18.8% of the total effect; the mediating effect of intolerance of uncertainty between chronic disease co-morbidity and physical and mental health of family members in older adults was -0.041, accounting for 33.5% of the total effect. 【Conclusion】 During closed management in a nursing facility, the physical and mental health of family members of older adults with chronic co-morbidities is poorer than that of family members of non-chronic co-morbidities. And it can lead to a decline in physical and mental health of family members through increased perceived stress and intolerance of uncertainty.
6.Gongji classification and treatment strategies for lateral clavicle fractures
Jianhong WU ; Jingming DONG ; Zhihua HAN ; Zhongguo FU ; Ming XIANG ; Weidong NI ; Lei ZHANG ; Xiaoming WU
Chinese Journal of Orthopaedics 2022;42(4):220-227
Objective:To establish a new classification of lateral clavicle fractures and to evaluate its clinical value.Methods:The data of 67 patients with lateral clavicle fractures admitted from January 2016 to December 2020 were included. Thirty-seven cases were from Shanghai First People's Hospital, including 22 males and 15 females, with an average age of 49.1 years (22-78 years). Thirty cases were from the Second Upper Limb Ward of Tianjin Hospital of Tianjin, including 20 males and 10 females, with an average age of 47.6 years (19-76 years). The ligament injury was determined by measuring the coracoclavicular space on Zanca view X-ray and the distance between the fracture fragment on the inferior surface of the 3D-CT and the distal end of the clavicle. All patients were classified according to the new classification (based on the measurement on Zanca view X-ray and 3D-CT reconstruction, the relationship between the fracture and the coracoclavicular ligament footprint, coracoclavicular ligament injury, the injury of the acromioclavicular joint and the stability of the fracture), conservative treatment is preferable for stable fractures, and surgical treatment for unstable fractures. Three experienced orthopaedic surgeons and three radiologists independently observed the imaging data of 67 patients with distal clavicle fractures, determined the fracture type according to the new classification, and randomly reclassified after 4 weeks interval. Finally, 15 cases were randomly selected for internal control (2 junior orthopedic physicians), and the ICC value was used to assess the reliability. Results:The lateral clavicle fractures were divided into 5 types according to the Gongji classification. Type 1: isolated conical tubercle avulsion fracture, and the fracture line is located medial to the coracoid process; Type 2: complete involvement of the trapezoid & conical ligament at the clavicle insertion, and the fracture line extends to the middle of the clavicle, mean while the acromioclavicular joint is intact; Type 3: fracture fragments on the inferior surface involving the trapezoidal/conical ligament, respectively; Type 4: rupture of the conical ligament, and avulsion fracture of the trapezoid ligament; Type 5: conical ligament intact, and avulsion fracture of clavicle insertion of the trapezoid ligament. There were 18 cases of type 1, 4 cases of type 2, 8 cases of type 3, 32 cases of type 4, and 5 cases of type 5. The inter-observer and intra-observer agreement of all included cases was good (inter-group: first ICC=0.764, second ICC=0.778; intra-group: shoulder specialist ICC=0.782, radiologist ICC=0.750, internal control ICC=0.793). Types 1 and 2 fractures were fixed with anatomical plate and coracoid anchor. Type 3 and 4 fractures were fixed with clavicle hook plate and coracoid anchor. And type 5 underwent conservative treatment. At the last follow-up, all patients had no obvious shoulder joint instability and pain, and no internal fixation failure or fixation breakage was found. Conclusion:The Gongji classification has moderate reliability between observers and intra-observers, and the Gongji distal clavicle fracture classification has a good significance for evaluating the stability of the fracture and guiding the selection of the treatment.
7.Practice of communication strategies of health scientific popularization of menopausal women
Dongxia FU ; Linjuan MA ; Huijuan KONG ; Jianhong ZHOU
Chinese Journal of Hospital Administration 2021;37(2):135-138
This paper aims to push health scientific popular knowledge and carry out targeted patient health education for certain patients, based on the demand of health education for specific diseases and population. Taking the female climacteric health scientific popularization as an example, the authors summarized the practice of popularizing scientific education in a tertiary specialized hospital based on the cognitive level and health education needs of outpatients and the general public. A multidisciplinary health scientific popularization team was set up to communicate popular science knowledge to patients and other menopausal women in need through multi-channel and multi-platform forms. Such means include online ones, offline ones, and cooperation with various social organizations. The implementation of health scientific popularization mode meets the needs of patients and the general public. The implementation of this mode of health popularization could improve their self-health management ability and health accomplishment. It provides a good reference for public hospitals to carry out health science popularization.
8.Comparison of inhalational methoxyflurane (Penthrox®) and intramuscular tramadol for prehospital analgesia.
Kegan Jianhong LIM ; Zhi Xiong KOH ; Yih Yng NG ; Stephanie FOOK-CHONG ; Andrew Fu Wah HO ; Nausheen Edwin DOCTOR ; Nur Ain Zafirah Mohd SAID ; Marcus Eng Hock ONG
Singapore medical journal 2021;62(6):281-286
INTRODUCTION:
Treatment of pain is an important component of prehospital care. Inhalational analgesia agents have attractive strengths, but there is a paucity of studies comparing these with more conventional agents. We aimed to compare inhalational methoxyflurane and intramuscular (IM) tramadol as first-contact analgesia in the Singapore national ambulance service.
METHODS:
Ambulances were randomised to carry either methoxyflurane or IM tramadol for the first six months and crossed over to the other arm after six months. Patients aged ≥ 16 years, with acute pain arising from musculoskeletal trauma with Numerical Rating Scale (NRS) score ≥ 3 were enrolled. Variables included NRS reduction, time variables, adverse effects, Ramsay Sedation Scores, and patient and paramedic satisfaction scores on a Likert scale.
RESULTS:
A total of 369 patients were enrolled into this study, but 26 patients were excluded due to missing data. The methoxyflurane arm had a shorter median time taken from arrival at the scene to drug administration (9.0 [interquartile range 6.0-14.0] minutes vs. 11.0 [interquartile range 8.0-15.0] minutes). For patients who achieved reduction in NRS ≥ 3 within 20 minutes, those in the methoxyflurane arm took a shorter time. However, the methoxyflurane (46.7%) arm experienced lower proportion of patients not achieving NRS reduction ≥ 3 when compared to the tramadol (71.6%) arm after over 20 minutes. The methoxyflurane arm had significantly higher paramedic and patient satisfaction scores.
CONCLUSION
For the doses of medication used in this implementation study, methoxyflurane was superior in efficacy, speed of onset and administration, but had more minor adverse effects when compared to IM tramadol.
9.Interpretation of group standard for Clostridioides difficile infection diagnosis
Yuan WU ; Jinxing LU ; Zhongqiang YAN ; Yunxi LIU ; Wenpeng GU ; Xiaoqing FU ; Yingchun XU ; Anhua WU ; Haihui HUANG ; Zhiyong ZONG ; Dazhi JIN ; Jianhong ZHAO ; Ye CHEN ; Weiping LIU ; Weiguang LI
Chinese Journal of Epidemiology 2021;42(1):64-67
Clostridioides difficile is a key pathogen of antibiotic related diarrhea and hospital associated infection, causing several outbreaks in Europe and North Americans and resulting in severe disease burden. However, the standardized diagnostic principle and detection specifications in C. difficile infection (CDI) survey are limited in China, and the infection rate and disease burden of CDI in China are unclear. Therefore, National Institute for Communicable Disease Control and Prevention,National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, together with another 11 institutions, draft the group standard entitled "Diagnosis of Clostridium difficile infection (T/CPMA 008-2020)" of Chinese Preventive Medicine Association. Based on the principle of "legality, scientificity, advancement, and feasibility", this standard clarifies risk factors, diagnosis principles, diagnoses and differential diagnoses in order to improve the accuracy of CDI diagnosis in clinical practice, guide the surveillance for CDI, and understand the infection rate and disease burden of CDI in China .
10.Effects of focused solution model combined with active psychological intervention on prognosis of patients with acute mastitis during lactation
Chinese Journal of Modern Nursing 2021;27(25):3483-3486
Objective:To explore effects of targeted nursing combined with positive psychological intervention on prognosis of patients with acute mastitis during lactation under the focused solution model.Methods:A total of 180 patients with acute mastitis during lactation who were admitted to the Fifth Affiliated Hospital of Zhengzhou University from June 2018 to January 2020 were randomly divided into the observation group ( n=92) and the control group ( n=88) . Patients in both groups were given routine nursing intervention for lactation acute mastitis. The control group was given positive psychological intervention on this basis, and the observation group was given targeted nursing based on focused solution mode on the basis of the control group. The differences in prognostic effects of patients were compared between the two groups. State-Trait Anxiety Inventory (STAI) and Edinburgh Postnatal Depression Scale (EPDS) were used to observe changes of mental state scores before and 2 weeks after intervention. Results:The treatment time of the observation group was shorter than that of the control group, the incidence of breast abscess was lower than that of the control group, and the rate of continued breastfeeding was higher than that of the control group. The differences were statistically significant ( P<0.05) . After 2 weeks of intervention, scores of S-AI and T-AI in STAI and EPDS of patients of the two groups were lower than before the intervention, and scores of the observation group were lower than those of the control group ( P<0.05) . Conclusions:Targeting nursing combined with positive psychological intervention under the focused solution mode can effectively shorten the treatment time, improve the treatment effect and relieve anxiety and depression of patients.

Result Analysis
Print
Save
E-mail