1.Chaihu Shugansan Combined with Ferulic Acid Regulates BDNF/TrkB Signaling Pathway and Monoamine Neurotransmitters in Frontal Cortex of Rat Model of CUMS
Yuexin LI ; Zhijing ZHANG ; Ziyi GUO ; Di YAN ; Xueyan HU ; Jianping YAO
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(15):28-37
ObjectiveTo observe the antidepressant effect of Chaihu Shugansan combined with ferulic acid on the rat model of chronic unpredictable mild stress (CUMS) and explore the mechanism from the histomorphology of frontal cortex, expression of key molecules in the brain-derived neurotrophic factor (BDNF)/tyrosine kinase receptor B (TrkB) signaling pathway, and changes in monoamine neurotransmitter levels. MethodsSixty adult male SD rats were randomized into six groups (n=10): blank control, depression model, Chaihu Shugansan (3.3 g·kg-1·d-1), ferulic acid (50 mg·kg-1·d-1), Chaihu Shugansan (3.3 g·kg-1·d-1) + ferulic acid (50 mg·kg-1·d-1), and fluoxetine (2.1 mg·kg-1·d-1). Rats in other groups except the blank control group were subjected to a mild chronic unpredictable stress stimulus every day. Seven stimuli were used, including fasting with free access to water for 24 h, water deprivation with free access to food for 24 h, wetting the bedding with water in the cage, restraint for 3 h, tail clamping for 1 min, swimming in ice water at 4 ℃, and day and night reversal. Each stimulus was used 1 to 3 times, and the modeling lasted for a total of 21 days. At the same time of stimulation, rats in each medication group were treated with corresponding agents by gavage, while those in the blank control group and the depression model group received equal volumes of normal saline by gavage. The open field test, sucrose preference test, and forced swimming test were conducted before and after modeling. The rats were anesthetized by intraperitoneal injection of 3% pentobarbital sodium, and the frontal cortex was isolated on ice. The mRNA and protein levels of BDNF, TrkB, and cyclic adenosine monophosphate-responsive element-binding protein (CREB) in the frontal cortex were determined by Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR) and Western blot, respectively. The levels of monoamine neurotransmitters 5-hydroxytryptamine (5-HT), dopamine (DA), and norepinephrine (NE) in the frontal cortex were determined by enzyme-linked immunosorbent assay. Light microscopy was employed to observe the histopathological changes in the frontal cortex. ResultsCompared with the blank control group, the depression model group showed reduced body mass (P<0.05, P<0.01), decreased number of crossings and rearings in the open field test and sucrose preference (P<0.01), prolonged time of immobility in the forced swimming test (P<0.01), reduced neuronal cells, increased necrotic cells, and darkening cell staining in the frontal cortex, down-regulated mRNA and protein levels of BDNF, TrkB, CREB, and lowered levels of 5-HT, NE, and DA in the frontal cortex (P<0.01). Compared with the depression model group, each intervention group showed improved general state, increased body mass (P<0.05), increased number of crossings (P<0.05), shortened immobility time in the forced swimming test (P<0.01), increased neuronal cells, reduced necrotic cells, and lightened cellular staining in the frontal cortex, up-regulated mRNA and protein levels of BDNF, TrkB and CREB, and elevated levels of 5-HT, NE, and DA in the frontal cortex (P<0.01). Moreover, the Chaihu Shugansan + ferulic acid group outperformed the Chaihu Shugansan group and the ferulic acid group in increasing the body mass and the 5-HT content in the frontal cortex (P<0.05). The combination group outperformed the Chaihu Shugansan group regarding the number of rearings and up-regulation in the mRNA level of BDNF in the frontal cortex (P<0.05), and it was superior to the ferulic acid group in terms of shortening the immobility time in the forced swimming test, up-regulating the mRNA levels of BDNF, TrkB, and CREB and the protein levels of BDNF and CREB in the frontal cortex, and increasing the DA content in the frontal cortex (P<0.05). ConclusionChaihu Shugansan combined with ferulic acid can exert antidepressant effect on the rat model of CUMS by regulating the BDNF/TrkB signaling pathway and monoamine neurotransmitter content in the frontal cortex. Moreover, the antidepressant effect of Chaihu Shugansan combined with ferulic acid was more significant than that of Chaihu Shugansan and ferulic acid used alone.
2.Analysis of non-targeted variants by invasive prenatal diagnosis for pregnant women undergoing preimplantation genetic testing
Si LI ; Ziyi XIAO ; Chenyu GOU ; Xiaolan LI ; Yijuan HUANG ; Yuanqiu CHEN ; Shujing HE ; Zhiqiang ZHANG ; Zi REN ; Song GUO ; Weiying JIANG ; Yu GAO
Chinese Journal of Medical Genetics 2024;41(11):1283-1289
Objective:To compare the results of invasive prenatal diagnosis and preimplantation genetic testing (PGT) and explore the underlying mechanism.Methods:Clinical data of pregnant women undergoing PGT and invasive prenatal diagnosis at the Sixth Affiliated Hospital of Sun Yat-sen University from January 2019 to December 2022 were collected. The results of PGT and invasive prenatal diagnosis were compared, and the outcomes of pregnancies were followed up. This study has been approved by the Medical Ethics Committee of the the Sixth Affiliated Hospital of Sun Yat-sen University (No. 2022SLYEC-491).Results:A total of 172 couples were included in this study, and 26 non-targeted variants were discovered upon prenatal diagnosis, including 10 cases (38.5%) by chromosomal karyotyping, 15 (57.7%) by chromosomal microarray analysis (CMA), and 1 (3.8%) by whole exome sequencing. The 10 karyotypic anomalies had included 6 chromosomal polymorphisms, 2 chromosomal mosaicisms, 1 paternally derived translocation, and 1 missed maternal chromosomal inversion. CMA has identified 15 copy number variations (CNVs), which included 11 microdeletions and microduplications, 3 loss of heterozygosity, and 1 low-level mosaicism of paternal uniparental disomy. One CNV was classified as pathogenic, and another one was likely pathogenic, whilst the remaining 13 were classified as variants of uncertain significance. Therefore, 8.7% of CNVs was detected by invasive prenatal diagnosis after PGT. 92.3% (24/26) of the non-targeted variants have been due to technological limitations of next-generation sequencing (NGS).Conclusion:Invasive prenatal diagnosis after PGT can detect non-targeted variants, which may further reduce the incidence of birth defects.
3.Evaluation of Animal Models of Dilated Cardiomyopathy Based on Clinical Characteristics of Traditional Chinese and Western Medicine
Lichong MENG ; Jin GUO ; Ziyi WANG ; Zhixi HU
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(20):194-202
The prevalence of dilated cardiomyopathy (DCM) has been increasing year by year,which seriously endangers the physical and mental health of patients. Establishing an animal model that conforms to the clinical characteristics of the disease is a prerequisite for conducting experimental research on DCM. This study sorted out and summarized the commonly used DCM animal models and evaluated the degree of consistency between the models and clinical practice based on the etiology and pathogenesis of traditional Chinese and western medicine and clinical diagnostic criteria. The models with high consistency with western medicine include immune models,drug toxicity models,and tachycardia models,while the models with high consistency with traditional Chinese medicine include drug toxicity models,gene correlation models,and tachycardia models. With consideration of the characteristics of the symptoms,consistency,and their respective advantages and disadvantages,the more ideal models are drug toxicity models,tachycardia models,and gene correlation models. In addition to evaluating the clinical consistency of traditional Chinese and western medicine in DCM animal models,this study also analyzed the advantages and disadvantages of existing DCM animal models,existing problems,and observation indicators of the models and pointed out the lack of standardized and unified syndrome model differentiation standards. Due to the complexity of the disease and the unclear pathogenesis,there are few studies on DCM models,and there is room for improvement. On this basis,four improvement directions are proposed to make the animal models as close to the clinical pathological and physiological processes as possible,so that the combination of disease and syndrome in animal models is more practical. These animal models can provide an experimental basis for the pathogenesis,drug intervention,efficacy evaluation,and scientific research of DCM and better serve scientific research and clinical practice.
4.Developmental trajectory and interaction between loneliness and social support among middle school students
Chinese Journal of School Health 2024;45(11):1604-1608
Objective:
To analyze the developmental trajectories of middle school students loneliness and social support, as well as to explore the interaction between loneliness and social support, so as to provide the evidence based support for the mental health development of adolescents.
Methods:
A total of 989 first year students from four public middle schools in Xiangxi Tujia and Miao Autonomous Prefecture, Hunan Province were selected for three follow up surveys by a cluster random sampling method (T1:March 2023, T2:June 2023, T3:December 2023). The UCLA Loneliness Scale-20 (ULS-20) and Social Support Scale for University Students (SSSUS) were employed for questionnaire data collection. The growth mixture modeling was utilized to test the developmental trajectories of loneliness and social support among middle school students, while the cross lagged analysis was performed to investigate their mutual influence.
Results:
The scores for loneliness and social support in T1, T2 and T3 were (43.1±5.8, 42.5± 6.8 , 42.0±6.9; 55.9±12.0, 60.7±15.7, 60.4±16.7), respectively. Correlational analysis revealed a significant negative correlation between loneliness levels (T1, T2, T3) and social support (T1, T2, T3) ( r =-0.47 to -0.36, P <0.01). Growth mixture modeling indicated a linear declining trend of middle school students loneliness, and the developmental trajectory of social support showed a linear increasing trend, with significant individual differences in initial levels and rates of change ( P <0.05). Cross lagged analyses revealed that loneliness levels at T1 negatively predicted social support scores at T2 ( β =-0.16), and loneliness levels at T2 negatively predicted social support scores at T3 ( β =-0.12) ( P <0.05). Additionally, prior loneliness positively predicted its subsequent levels, with path coefficients of 0.58 and 0.47, respectively ( P <0.05). Social support scores at T1 negatively predicted loneliness levels at T2 ( β =-0.10), while scores at T2 negatively predicted loneliness levels at T3 ( β =-0.15) ( P <0.05). Prior loneliness also positively predicted its subsequent levels, with path coefficients of 0.43 and 0.44, respectively ( P <0.05).
Conclusion
The developmental trajectory of middle school students loneliness demonstrates a decreasing trend, while that of social support exhibits a linear increasing trend, indicating a longitudinal causal relationship between loneliness and social support.
5.Research progress on epilepsy after reperfusion therapy in ischemic stroke
Yue LIU ; Shuda CHEN ; Siqing CHEN ; Xinxin PENG ; Sijing YIN ; Dingju LONG ; Chengzhe WANG ; Xintong GUO ; Guanzhong NI ; Ziyi CHEN
Chinese Journal of Nervous and Mental Diseases 2024;50(10):619-626
There is no unified international guidelines or consensus on seizures and epilepsy following acute stroke reperfusion therapy so far.In this review,we briefly summarize its definitions and mechanisms.Post stroke epilepsy after reperfusion treatment is defined as patients with ischemic stroke who have received intravenous thrombolysis and/or endovascular therapy,without other definitive causes or epilepsy history before stroke,have at least two epileptic seizures occurred within 7 days of stroke onset,or at least one epileptic seizures occurred within 30 days of stroke onset.The incidence rate of epilepsy after intravenous thrombolysis is about 6.4%-20.6%,and arterial thrombectomy is about 5%.The pathophysiological mechanism of post stroke epilepsy after reperfusion treatment may be related to local hyperfusion,epileptogenic properties of tPA and hemorrhagic transformation.Higher stroke severity,cortical involvement,middle cerebral artery infarction,and early post-stroke seizures may be predictive factors for post-stroke epilepsy after reperfusion therapy.Levetiracetam and lamotrigine may be effective drugs for post-stroke epilepsy after reperfusion therapy.Sustained seizures after thrombolysis may increase the risk of death.
6.Clinicopathological and molecular genetic features of neuromuscular choristoma-associated desmoid type fibromatosis
Rongfang DONG ; Wen GUO ; Nan LI ; Ziyi WANG ; Xiaoqi SUN ; Yi DING
Chinese Journal of Pathology 2024;53(7):685-690
Objective:To investigate the clinicopathological and genetic characteristics of neuromuscular choristoma-associated desmoid type fibromatosis (NMC-DF).Methods:The clinical morphological and immunohistochemical features of 7 NMC-DF cases diagnosed from January 2013 to January 2023 in Beijing Jishuitan Hospital were retrospectively analyzed. A series of neuromuscular choristoma and neuromuscular choristoma-associated desmoid type fibromatosis were evaluated for CTNNB1 mutations, and hotspot mutations for CTNNB1 were tested in 4 NMC-DF cases using Sanger sequencing.Results:The tumors were collected from 3 females and 4 males, aged 1 to 22 years (mean 7.1 years), involving the sciatic nerve ( n=4), brachial plexus ( n=2) or multiple nerves ( n=1). The course of the disease spanned from 3 months to 10 years. Two cases were recurrent tumors. All the 7 NMC cases showed endoneurial intercalation of mature skeletal muscle fibers among the peripheral nerve fascicles, and the histologic features of the NMC-DF were strikingly similar to the conventional desmoid-type fibromatosis. By immunohistochemistry, all NMC and NMC-DF cases showed aberrant nuclear staining of β-catenin (7/7), the muscle cells in NMC were intensely immunoreactive for desmin, and the admixed nerve fibers were highlighted by NF and S-100 (7/7). Four NMC and NMC-DF had CTNNB1 mutations, 3 c.121A>G (p.T41A) and 1 c.134C>T (p.S45F). Follow-up of the 7 cases, ranging from 22 to 78 months, showed tumor recurrence in 2 patients at 3 and 8 months respectively after the first surgical resection, of which 1 patient underwent above-knee amputation. No recurrence occurred in other cases with tumor excision and neurological reconstruction surgery. There was no metastasis occurred in the 7 cases. Conclusions:NMC is a rare congenital lesion with differentiated mature skeletal muscle tissue found in peripheral nerve fascicles, and approximately 80% of patients with NMC develop a soft tissue fibromatosis. CTNNB1 mutation in the Wnt signaling pathway may be involved in the pathogenesis of NMC and NMC-DF, and S45F mutations seems to have a higher risk of disease progression.
7.Analysis of the diagnostic efficiency of wrist joint ulnar deviation supination 45° palmar oblique position for scaphoid waist fracture and displacement
Shifei CHEN ; Jun ZHANG ; Shuman HAN ; Wenjuan WU ; Zhiwei ZHONG ; Jing LI ; Zhe GUO ; Huizhao WU ; Ziyi QIAO
Journal of Practical Radiology 2024;40(5):805-808
Objective To investigate the clinical application value of wrist joint ulnar deviation supination 45° palmar oblique posi-tion in the diagnosis of scaphoid waist fracture and displacement.Methods The imaging and clinical data such as digital radiography(DR),CT of 93 wrist joint trauma patients were analyzed.The four position views including wrist joint anteroposterior+lateral view,scaphoid position,wrist joint ulnar deviation supination 45° palmar oblique position,scaphoid position+wrist joint ulnar devia-tion supination 45° palmar oblique position were analyzed by three readers.The consistency of the evaluation among different readers and the diagnostic efficiency of the diagnosis of scaphoid fracture and displacement were compared.Results The inter-observer agreement,sensitivity,specificity,accuracy,and other diagnostic efficiency of scaphoid waist fracture and displacement was evaluated,wrist joint ulnar deviation supination 45° palmar oblique position+scaphoid position and wrist joint ulnar deviation supination 45° palmar oblique position were better than those of scaphoid position and wrist joint anteroposterior+lateral view.The combination of wrist joint ulnar deviation supination 45° palmar oblique position+scaphoid position obtained the best diagnostic efficiency.Conclusion The wrist joint ulnar deviation supination 45° palmar oblique position shows the long axis of the scaphoid,which has a high diagnostic efficiency in the diagnosis of scaphoid waist fracture and displacement and would be used as a useful supplement to other scaphoid imaging.
8.Study on Medication Law of National Patented Chinese Herbal Prescriptions for the Treatment of Benign Prostatic Hyperplasia Based on Data Mining
Lichong MENG ; Kun LIAN ; Jin GUO ; Ziyi WANG ; Zhixi HU
Chinese Journal of Information on Traditional Chinese Medicine 2024;31(11):60-66
Objective To explore the prescribing law of TCM in national patents for the treatment of benign prostatic hyperplasia(BPH);To provide a reference for clinical medication.Methods Data on TCM compound prescriptions for the treatment of BPH were retrieved from the China National Intellectual Property Administration(CNIPA)patent retrieval and analysis system,covering the period from January 1,2000,to October 31,2023.The frequency,efficacy category,properties and tastes,meridian tropism,core complex co-occurrence network,and potential TCM clusters mentioned in the patents were analyzed using Excel 2016,SPSS Modeler 18.0,SPSS Statistics 27,and Cytoscape 3.10.0 software.Results A total of 182 patents were included,involving 404 kinds of Chinese materia medica,with a total frequency of 2054 times.Among them,22 kinds of Chinese materia medica had a frequency of≥20,with the most frequently used Chinese materia medica being Astragali Radix,Glycyrrhizae Radix et Rhizoma,Phellodendri Chinensis Cortex,Epimedii Folium,Salviea Miltiorrhizae Radix et Rhizoma,Plantaginis Semen,Poria,Vaccariae Semen,Alismatis Rhizoma and Paeoniae Radix Rubra.The high-frequency herbs primarily consisted of tonifying herbs(267 times,13.00%),blood circulation-activating and stasis-resolving herbs(216 times,10.52%),and diuretic and dampness-percolating herbs(147 times,7.16%).The properties of the herbs were mainly sweet and cold,and they were mainly attributed to the liver and kidney meridians.Association rule analysis yielded 10 common drug pairs,including Cornus Officinalis-Rehmannize Radix et Praeparata,Curcumae Rhizoma-Sparganii Rhizoma,and Astragali Radix-Codonopsis Radix.The drug combination with the highest confidence was Angelicae Sinensis Radix-Phellodendri Chinensis Cortex-Glycyrrhizae Radix et Rhizoma.Clustering analysis revealed five drug combinations,while potential TCM clustering analysis identified five groups,among which the"Zingiberis Rhizoma-Os Draconis-Angelicae Pubescentis Radix-Scallion-Rice Bran-Speranskiae Herba"network demonstrated the highest degree of interconnection(Score=6).Conclusion The high-frequency herbs in national patents for the treatment of BPH with TCM compound prescriptions mainly focus on tonifying the spleen and kidney,activating blood circulation to remove stasis,and clearing heat and draining dampness,providing a reference for clinical practice.
9.Quality of life among 244 patients with occupational pneumoconiosis in Jinhua City
LUO Jinbin ; HE Xiaoqing ; CHEN Qiang ; GUO Zhen ; LUO Ziyi
Journal of Preventive Medicine 2023;35(6):517-521
Objective:
To investigate the quality of life among patients with occupational pneumoconiosis in Jinhua City, Zhejiang Province, so as to provide insights into improving the quality of life among patients with occupational pneumoconiosis.
Methods:
Patients with occupational pneumoconiosis in Jinhua City from 2009 to 2021 were retrieved from the National Occupational Disease and Health Risk Factors Monitoring Information System. Participants' demographics, diagnosis of pneumoconiosis, stage of pneumoconiosis, pulmonary function and medical expense were collected through questionnaire surveys, and the quality of life was measured using a Chinese version of the Short-Form Health Survey (SF-36). The quality of life was descriptively analyzed among patients with occupational pneumoconiosis by disease stage, pulmonary function, expense for disease diagnosis and treatment and educational level.
Results:
A total of 244 patients with occupational pneumoconiosis were enrolled, including 225 men (92.21%). The participants had a mean age of (75.20±9.42) years, and mean duration from dust contact to pneumoconiosis onset of (13.11±9.89) years. The scores for physical functioning, role-physical, bodily pain, general health, vitality, social functioning, role-emotional, and mental health were (64.03±31.22), (45.14±44.22), (56.34±26.60), (40.80±19.80), (59.14±17.35), (68.41±19.67), (47.03±44.08) and (61.15±17.06) points among patients with occupational pneumoconiosis, which were all lower than the national constant (P<0.05). Lower scores were measured for physical functioning [(31.17±23.40) points], bodily pain [(45.21±19.50) points] and vitality [(47.00±20.70) points] among patients with stage Ⅲ occupational pneumoconiosis, for physical functioning [(32.27±24.24) points], role-physical [(12.88±30.70) points], bodily pain [(37.44±20.43) points], general health [(14.76±17.17) points], vitality [(38.79±19.33) points], social functioning [(53.33±17.08) points], role-emotional [(9.09±26.71) points], and mental health [(53.21±17.25) points] among occupational pneumoconiosis patients with severe pulmonary function damages, and for physical functioning [(30.97±27.40) points], bodily pain [(37.77±24.34) points], general health [(19.10±18.62) points], vitality [(38.39±23.78) points], social functioning [(55.89±21.00) points] and mental health [(55.35±20.35) points] among occupational pneumoconiosis patients that had personal payments for pneumoconiosis diagnosis and treatment expenses exceeding 30% of annual household incomes, while higher scores were measured for physical functioning [(66.36±17.33) points] and role-physical [(59.09±45.10) points] among occupational pneumoconiosis patients with an educational level of high school and above (all P<0.05).
Conclusions
The quality of life was low among occupational pneumoconiosis patients in Jinhua City from 2009 to 2021. Stage of pneumoconiosis, pulmonary function, medical expenses and educational level were identified as factors affecting the quality of life among occupational pneumoconiosis patients in Jinhua City.
10.Literature analysis of ocular adverse drug reactions related to dupilumab
Ziyi FU ; Tingting XIE ; Daihong GUO
China Pharmacy 2023;34(14):1744-1747
OBJECTIVE To analyze the clinical manifestation and characteristics of ocular adverse drug reaction (ADR) related to dupilumab, so as to provide reference for clinically safe drug use. METHODS Retrieved from CNKI, Wanfang data, VIP and PubMed databases, the case reports about ocular ADR caused by dupilumab were collected, and then analyzed statistically in terms of gender, age, primary disease, drug use, occurrence time of ADR, main clinical manifestations, treatment or outcome, etc. RESULTS A total of 20 pieces of literature were selected, involving 46 patients, among which there were 29 males and 17 females. Mainly patients were under 60 years old. The results of the association evaluation was given as follows: 13 were “very likely” and 33 were “likely”. All patients were treated with dupilumab for atopic dermatitis (AD) without off-label medication. The occurrence time of ADR was 2 weeks to 2 years after administration, mainly within 6 months after medication. All patients received dupilumab monotherapy except that 3 patients with hypertension and 1 patient with chronic obstructive pulmonary disease and human immunodeficiency virus received other drugs simultaneously. Twenty-eight patients had a history of allergic disease, and 11 patients had a history of eye disease. Ocular ADRs were mainly conjunctivitis and uveitis, and the clinical manifestations mainly included conjunctival congestion, swelling, eye secretions, etc. Ten patients developed severe ADR, including uveitis, severe conjunctivitis, and tear point stenosis; 45 patients were improved after symptomatic treatment. AD, serious initial symptoms of AD, allergic disease and underlying ocular diseases might be the high-risk factors of ocular ADR caused by dupilumab. CONCLUSIONS Whether the patient has the history of allergic diseases and basic eye diseases should be asked in detail before clinical use of dupilumab. When using the drug, attention should be paid to monitoring whether the patient has intraocular inflammation, be alert to the occurrence of new or serious ADR, and give timely symptomatic treatment to ensure the safety of drug use.


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