1.Fufang Kangjiaolv Capsules Treat Anxiety in Rat Model of Chronic Restraint Stress via Microbiota-gut-brain Axis
Wenxin FAN ; Tingyue JIANG ; Yu WANG ; Ge ZHANG ; Yifan LU ; Mengmeng LIU ; Jiayuan LI ; Renzhi MA ; Jinli SHI
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(4):95-107
ObjectiveTo observe the intervention effect of Fufang Kangjiaolv capsules on anxiety-like behaviors in the rat model of chronic restraint stress (CRS) and explore the mechanism underlying the anti-anxiety effect via the microbiota-gut-brain axis. MethodsRats were assigned into blank, model, positive drug (diazepam, 1 mg·kg-1), and low-, medium-, and high-dose (0.75, 1.5, 3 g·kg-1, respectively) Fufang Kangjiaolv capsules groups. After 14 days of administration, the elevated plus maze test, open field test, light and dark box test, and marble burying test were performed. Hematoxylin-eosin staining was employed to observe the pathological changes in the hippocampus and colon of rats, and Nissl staining was conducted to observe the damage of hippocampal neurons. The gut microbiota was analyzed by 16S rRNA gene sequencing. Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR) was employed to determine the mRNA levels of zonula occludens-1 (ZO-1) and occludin in the colon of rats. The levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-1β (IL-1β) in the colon, serum, and hippocampus were determined by enzyme-linked immunosorbent assay. Western blot was employed to determine the protein levels of ZO-1, occludin, nuclear factor-κB p65 (NF-κB p65) in the colon tissue and NF-κB p65 and brain-derived neurotrophic factor (BDNF) in the hippocampal tissue. ResultsCompared with the blank group, the model group showed reductions in the time and frequency ratio of rats entering the elevated plus maze, the time and frequency of rats entering the central area of the open field, the time of entering the open box, the times of passing through the light and dark box, and the number of unburied beads (P<0.05, P<0.01). Compared with the model group, Fufang Kangjiaolv capsules ameliorated the anxiety of the model rats to varying degrees, and the high-dose group had the best effect, with increases in the proportions of time and frequency of rats entering the open arm in the elevated plus maze (P<0.05), the number of rats entering the central area in the open field (P<0.05), the time of entering the open box, the times of passing through the light and dark boxes, and the number of unburied beads (P<0.01). Moreover, the high-dose group showed alleviated pathological damage of hippocampal neurons and colon. The results of 16S rRNA gene sequencing showed that the model group had increased relative abundance of Firmicutes, Deferribacterota, Romboutsia, and Phascolarctobacterium, while it had decreased relative abundance of Bavcteroidota and Lactobacillus. The drug administration groups showed increased relative abundance of Bavcteroidota, Bacteroides, norank f norank o Clostridia UCG-014, and Blautia and decreased relative abundance of Firmicutes and Deferribacterota. Compared with the blank group, the model group showed down-regulated protein and mRNA levels of ZO-1 and occludin in the colon (P<0.01), elevated levels of TNF-α, IL-6, and IL-β in the colon, serum, and hippocampus (P<0.01), up-regulated protein level of NF-κB p65 in the colon and hippocampus (P<0.01), and down-regulated protein level of BDNF in the hippocampus (P<0.05). Compared with the model group, high-dose Fufang Kangjiaolv capsules up-regulated the mRNA levels of ZO-1 and occludin in the colon (P<0.01), lowered the levels of TNF-α, IL-6, and IL-β in the colon, serum, and hippocampus (P<0.01), up-regulated the protein levels of ZO-1 (P<0.01) and occludin (P<0.05) in the colon, down-regulated the protein level of NF-κB p65 in the colon and hippocampus (P<0.05), and up-regulated the protein level of BDNF in the hippocampus. ConclusionFufang Kangjiaolv capsules can reduce the anxiety-like behaviors in the rat model of CRS by regulating the gut microbiota disturbance, up-regulating the expression of tight junction proteins in the colon, repairing intestinal mucosal mechanical barrier, and down-regulating NF-κB/BDNF signaling pathway, thereby reducing peripheral and central inflammation. This study proves the hypothesis that Fufang Kangjiaolv capsules play an anti-anxiety role via the microbiota-gut-brain axis, providing a new idea for further research.
2.Clinical Observation of Modified Zhigancao Tang in Treating Patients with Liver and Kidney Deficiency of Parkinson's Disease and Its Effect on Neuronal Signal-related Proteins
Yifo WEI ; Furong LYU ; Jia YAO ; Guonian LI ; Xianyi LUO ; Meng LUO ; Zhengzheng WEN ; Qiuqi LI ; Yihan LIU ; Linlin YANG ; Rui ZUO ; Wenxin DANG ; Fang MI ; Xiaoyan WANG ; Zhigang CHEN ; Fan LIU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(4):166-173
ObjectiveMicrotube associated protein-2 (MAP-2), alpha-tubulin (α-tubulin), and synaptophysin (SYP) are important proteins in neuronal signal communication. This paper observed the effects of modified Zhigancao Tang on the expression of serum α-Synuclein (α-Syn) and its oligomers, MAP-2, α-tubulin, and SYP of patients with liver and kidney deficiency of Parkinson's disease (PD), analyzed their correlation, and evaluated the therapeutic effect of modified Zhigancao Tang in patients with liver and kidney deficiency of PD based on α-Syn transmission pathway mediated by neuronal communication in vivo. MethodsA total of 60 patients with PD who met the inclusion criteria were randomly divided into a treatment group (30 cases) and a control group (30 cases). Both groups were treated on the basis of PD medicine, and the treatment group was treated with modified Zhigancao Tang. Both groups were treated for 12 weeks. The changes in UPDRS score, TCM syndrome score, and expression of serum α-Syn and its oligomers, MAP-2, α-tubulin, and SYP were observed before and after 12 weeks of treatment in each group. The correlation between the above-mentioned serum biological indexes and the levels of serum α-Syn and its oligomers was analyzed. ResultsAfter treatment, the TCM syndrome score, UPDRS score, UPDRS-Ⅱ score, and UPDRS-Ⅲ score of the treatment group were significantly decreased (P<0.05, P<0.01). The UPDRS score, UPDRS-Ⅱ score, and UPDRS-Ⅲ scores in the treatment group were significantly decreased compared with those in the control group after treatment (P<0.05). After treatment, the total effective rate of the control group was 63.3% (19/30), and that of the treatment group was 86.7% (26/30). The clinical effect of the observation group was better than the control group (Z=-2.03, P<0.05). The total effective rate of the observation group was better than that of the control group, and the difference was statistically significant (χ2=5.136, P<0.05). After treatment, the oligomer level of serum α-Syn and MAP-2 level in the treatment group were significantly decreased (P<0.05, P<0.01). The levels of serum α-Syn and its oligomers, as well as α-tubulin in the treatment group, were significantly decreased compared with those in the control group after treatment (P<0.05, P<0.01). Serum α-Syn was correlated with serum MAP-2 and α-Syn oligomer in patients with PD (P<0.05, P<0.01) but not correlated with serum SYP . Serum α-Syn oligomers of patients with PD were correlated with serum MAP-2 and α-tubulin (P<0.05, P<0.01) but not correlated with serum SYP level. Serum SYP of patients with PD was correlated with serum MAP-2 (P<0.05). ConclusionModified Zhigancao Tang has a therapeutic effect on patients with liver and kidney deficiency of PD by inhibiting the production of α-Syn oligomers and intervening α-Syn microtubule transport pathway in vivo.
3.Early clinical efficacy of Yiqi Tongluo Decoction on ischemic cerebrovascular disease after interventional therapy
Qinghua WANG ; Gesheng WANG ; Ruiping LI ; Can ZHENG ; Wenjing LI ; Jiaqi CHEN ; Kaihang GUO ; Xiaobo DONG ; Wenxin WANG ; Rongjuan GUO ; Le WANG
Journal of Beijing University of Traditional Chinese Medicine 2025;48(1):108-121
Objective:
To observe the clinical efficacy and safety of Yiqi Tongluo Decoction in the intervention of early traditional Chinese medicine (TCM) syndromes after ischemic cerebrovascular disease (ICVD) intervention.
Methods:
From October 2020 to July 2023, a randomized, double-blind, placebo-controlled study was conducted to include 60 patients with qi deficiency, blood stasis, and phlegm obstruction syndrome after ICVD interventional therapy. They were assigned to the Yiqi Tongluo Decoction treatment group (30 cases) and the TCM placebo routine treatment control group (30 cases) according to the randomized block design. Both groups received routine standardized treatment of Western medicine, including dual antiplatelet, lipid regulation, and control of risk factors for cerebrovascular disease. The treatment group was treated with Yiqi Tongluo Decoction based on the control group. The course of treatment was 60 days and follow-up was carried out 2 and 6 months after the operation. The improvement of qi deficiency syndrome, blood stasis syndrome, phlegm syndrome score and TCM syndrome score, modified Rankin score (mRS), Barthel index (BI) score, Fatty acid-binding protein 4 (FABP4) level, incidence of transient ischemic attack (TIA) and ischemic stroke (IS) and incidence of adverse reactions, Head and neck CT angiography (CTA) or digital subtraction angiography (DSA) examination were collected. The clinical efficacy of the patients 2 months after the operation was taken as the main outcome index to preliminarily evaluate the early and long-term efficacy of Yiqi Tongluo Decoction after the ICVD intervention. The early and long-term clinical efficacy and safety of Western medicine standardized treatment combined with TCM Yiqi Tongluo Decoction on patients with qi deficiency, blood stasis and phlegm obstruction syndrome after ICVD intervention were evaluated. The safety of Yiqi Tongluo Decoction in the treatment of patients after ICVD intervention with white blood cell (WBC), C-reactive protein (CRP), fibrinogen (FIB), plasminogen time (PT), recurrence of cerebral ischaemia and restenosis in patients at 2 and 6 months after treatment were evaluated.
Results:
Compared to the control group, the TCM syndrome scores for qi deficiency, blood stasis and phlegm syndrome in the treatment group reduced significantly, the clinical efficacy improved significantly, the mRS score and FABP4 were reduced, and the BI score was increased. Adverse events such as cerebral ischaemia were fewer in the treatment group than in the control group, but the difference was not statistically significant; levels of CRP, WBC and PT were reduced, and levels of FIB were reduced at 6 months post-treatment, all P<0.01, and images were intuitively compared. The treatment group was superior to the control group.
Conclusion
Yiqi Tongluo Decoction combined with Western medicine standard treatment can improve the early clinical efficacy of ICVD patients with qi deficiency, blood stasis and phlegm obstruction syndrome after interventional surgery, improve neurological impairment and daily living ability, reduce the state of qi deficiency syndrome, blood stasis syndrome and phlegm syndrome after interventional surgery, and improve the clinical efficacy of TCM. At the same time, it can reduce the level of FABP4, the target of atherosclerosis and restenosis after interventional surgery, reduce the level of inflammation after interventional surgery in patients with ICVD, regulate coagulation function, and reduce the incidence of long-term recurrence of cerebral ischemia after interventional surgery, with good safety.
4.Prognostic Significance of KMT2D Gene Mutation and Its Co-mutated Genes in Patients with Diffuse Large B-Cell Lymphoma
Mutibaier·MIJITI ; Xiaolong QI ; Renaguli·ABULAITI ; Wenxin TIAN ; Sha LIU ; Weiyuan MA ; Zengsheng WANG ; Li AN ; Min MAO ; Muhebaier·ABUDUER ; Yan LI
Cancer Research on Prevention and Treatment 2025;52(2):127-132
Objective To explore the clinical characteristics of patients with diffuse large B-cell lymphoma (DLBCL) accompanied with KMT2D gene mutation and the impact of its co-mutated genes on prognosis. Methods Clinical data of 155 newly diagnosed DLBCL patients were obtained. The second-generation sequencing method was used to detect 475 hotspot genes, including KMT2D mutation. Patients were divided into the KMT2D mutation group and KMT2D wild-type group based on the presence or absence of KMT2D gene mutation. Clinical characteristics, differences in co-mutated genes, and survival differences between the two groups were compared. Results The frequency of KMT2D mutation was 31%, which is predominantly observed in elderly patients (P=0.07) and less in the double-expressor phenotype (P=0.07). Compared with the KMT2D wild-type group, KMT2D gene mutation was associated with higher co-mutation rates of CDKN2A (OR=2.82, P=0.01) and BCL2 (OR=3.84, P=0.016), while being mutually exclusive with MYC gene mutation (OR=0.11, P=0.013). In univariate survival analysis, no statistically significant difference in overall survival (OS) was found between the KMT2D mutation group and the wild-type group (P=0.54). Further analysis of the prognostic significance of KMT2D with other gene mutations indicated that patients with KMT2DmutBTG2mut had poorer OS than those with KMT2Dwt BTG2mut (P=0.07) and KMT2Dwt BTG2wt (P=0.05). On the contrary, patients with KMT2Dmut CD79Bmut had better OS than those with KMT2Dmut CD79Bwt (P=0.09), with no prognostic impact observed for other co-mutated genes. Multivariate Cox regression analysis revealed that Ann Arbor stages Ⅲ and Ⅳ (HR=2.751, 95%CI: 1.169-6.472, P=0.02), elevated LDH levels (HR=2.461, 95%CI: 1.396-4.337, P=0.002), Ki-67 index>80% (HR=1.875, 95%CI: 1.066-3.299, P=0.029), and KMT2DmutBTG2mut(HR=4.566, 95%CI: 1.348-15.471, P=0.015) were independent risk factors for OS in patients with DLBCL (P<0.05). Conclusion DLBCL patients with KMT2D mutation often have multiple gene mutations, among which patients with a co-mutated BTG2 gene have poor prognosis.
5.Analysis of visual field manifestations of non-arteritic anterior ischemic optic neuropathy
Yue LI ; Ying WANG ; Wenxin JIAO ; Jilu LIN ; Jianing WANG
International Eye Science 2025;25(4):671-675
AIM: To observe the manifestations and distribution patterns of visual field in non-arteritic anterior ischemic optic neuropathy(NAION).METHODS: Retrospective observational study. The investigation encompassed 183 patients(246 eyes)diagnosed with NAION who were evaluated at the Neuro-Ophthalmology/Acupuncture Department within the Eye Hospital, China Academy of Chinese Medical Sciences from June 2018 to December 2023. Recorded clinical data covered demographic details, incidence, disease duration, presence of systemic diseases, and histories of tobacco and alcohol use, along with best-corrected visual acuity(BCVA), visual field index(VFI), type of visual field defect, and thickness of the peripapillary retinal nerve fiber layer(pRNFL).RESULTS: A total of 183 patients(246 eyes)were enrolled. The cohort consisted of 101 males and 82 females; 120 exhibited unilateral symptoms, while 63 showed bilateral symptoms, with a mean age of 56.20±9.78 years(range 29-81 years). The types of visual field defects observed were varied: 90 eyes(36.6%)had diffuse loss, 63 eyes(25.6%)experienced inferior hemifield loss, 32 eyes(13.0%)displayed ring scotomas, 22 eyes(8.9%)had arcuate scotomas, 11 eyes(4.5%)presented with quadrant defects, 15 eyes(6.1%)had sectorial or wedge defects, and 13 eyes(5.3%)showed superior hemifield loss. The BCVA(LogMAR)and VFI of patients with diffuse visual field loss were poorer than patients with other types of visual defects(all P<0.05). There were statistically significant differences in visual field defects among patients of different genders and ages(all P<0.05). However, history of hypertension, diabetes, hyperlipidemia, sleep apnea and other systemic diseases, history of smoking and alcohol, and course of disease did not show specificity in the NAION visual field(all P>0.05).CONCLUSION:NAION manifests with a broad spectrum of visual field impairments across different genders, age, and levels of visual functionality. Extensive future research is necessary to identify additional reasons influencing the types of visual field damage in NAION.
6.Analysis of the causes for abnormal dissolution of lansoprazole enteric-coated tablets by multiple techniques and different dimensions
Wenxin LIU ; Yan LI ; Yaozuo YUAN ; Huanhuan JIA ; Minhui CHEN ; Jinlin ZHANG
Journal of China Pharmaceutical University 2024;55(2):224-229
Abstract: This study aims to find out the causes for the dissolution of unqualified samples found during evaluation sampling of lansoprazole enteric-coated preparations by the laser infrared imaging system and orbitrap high resolution mass spectrometry, with suggestions for improvement. Lansoprazole enteric-coated preparations were tested by current standard, the dissolution of a batch of samples was below the limit and other items were in line with the standard. Considering that this product is unstable to acid and alkali, the following exploratory experiments were designed from different dimensions, based on the conclusion of the unannounced inspection of the company, to explore the reasons for the unqualified batch, including the influence of high-temperature and high-humidity storage environment on the key quality properties of the sample, the influence of 2-hour acid resistance test on dissolution result, the imaging of the core and the measure of coating layer thickness, the optimization of chromatographic conditions of related substances, and the analysis of the source of impurities. It was found that improper storage in circulation and poor coating process caused the low dissolution of this batch: the high-temperature and high-humidity storage environment possible in the circulation process led to the decreasing efficacy of disintegrating agent in the samples and thus the difficulty to release the active pharmaceutical ingredient fully; the coating solution could not be uniformly sprayed on the core, resulting in thin isolation layer and different thickness, which then affected the protection of the main drug against acid degradation. The above two reasons together resulted in unqualified dissolution of this batch. The overall quality of lansoprazole enteric-soluble preparation is good, but the formulation and process in some companies need to be optimized; and the temperature and humidity in the circulation process need to be controlled in strict accordance with the regulations.
7.Study on the Relationship Between OAT1 Expression and Renal Osteodystrophy in Rats with Chronic Renal Failure
Wenjuan SHEN ; Wenxin LIANG ; Qing LI ; Hongfang XU ; Weiqin ZHANG ; Haixin LI
Journal of Kunming Medical University 2024;45(2):32-38
Objective To investigate the changes of OAT expression in bone cells in chronic renal failure(CRF)and involved mechanism,and to explore the effect of OAT expression on bone metabolism.Methods Ra-ndomly divide the rats into a control group(n=6)and a model group(n=6).The model group established a rat chronic renal failure model using"single nephrectomy+adenine gavage"method,and the red blood cell(RBC)and hemoglobin(HGB)of the rat body were measured using a blood routine analyzer;Measure indicators such as creatinine(Cr),urea nitrogen(BUN),uric acid(UA),blood calcium(Ca2+),and blood phosphorus(P3+)using a fully automated biochemical analyzer;Pathological examination of rat kidneys;X-ray examination of rat tibia;Immunohistochemical examination of bone tissue OAT1 level.Results The bone density of the model group rats is lower than that of the control group;The calcium and phosphorus metabolism of rats in the model group was in metabolic disorder,and the OAT1 value of bone tissue binding was much lower than that of the control group(P= 0.0018),which was statistically significant.(P=0.0018)Conclusion Chronic renal failure affected the binding ability of OAT1 in bone tissue,leading to the metabolic disorder for calcium absorption and phosphorus metabolism,thus aggravating renal osteodystrophy(P<0.05).
8.Research advances on the applications of functional magnetic resonance imaging for evaluating kidney transplant function
Wenxin LI ; Jun ZHANG ; Feng GAO ; Tian GAN
Chinese Journal of Organ Transplantation 2024;45(1):57-61
After kidney transplantation , timely detection of changes in transplanted kidney function may guide clinical managements and prevent or delay irreversible damage to transplanted kidney. Functional magnetic resonance imaging (fMRI) of transplanted kidney is a promising non-invasive technique of acquiring microstructural and microfunctional profiles of transplanted kidney. In recent years, various diffusion imaging modalities, arterial spin labeling (ASL) and blood oxygen level dependent-magnetic resonance imaging (BOLD-MRI) have gradually been applied for transplant kidneys. Transplant kidney function may be evaluated non-invasively from such microscopic perspectives as water molecule diffusion, blood flow perfusion and blood oxygen level. This review focused upon evaluating the renal function and identifying the causes of the renal function decline of transplanted kidney through various fMRI techniques and provide new rationales for clinical diagnosis.
9.Dynamic changes of platelet-related indicators in infants with cow′s milk protein allergy
Wenxin DONG ; Hua ZHANG ; Zailing LI
Chinese Journal of Child Health Care 2024;32(1):93-97
【Objective】 To dynamically monitor and analyze the changes of platelets and related indicators in infants with cow′s milk protein allergy (CMPA) during clinical treatment, in order to provide clues for further diagnosis and treatment of CMPA. 【Methods】 From August to November in 2022, 59 children aged from 1 month to 3 years old with CMPA in the pediatric outpatient clinic were selected as the CMPA group, and 29 healthy children who took physical examination were selected as the control group. The differences in platelet related indicators from a routine blood test were compared between the two groups, and their diagnostic value for CMPA was analyzed by receiver operating characteristic (ROC) curves. 【Results】 The mean platelet count (PLT) and plateletcrit (PCT) at baseline in the CMPA group were (374.68±113.21)×109/L and 0.37±0.10, significantly higher than those in control group[(271.07±40.32)×109/L, 0.26±0.05] (t=6.27, 6.43, P<0.001). In the CMPA group, after treatment, the mean PLT level was (316.39±94.68)×109/L, and the mean PCT level was 0.31±0.10, indicating a statistically significant decrease in PLT and PCT levels after treatment compared to baseline (t=4.32,4.75,P<0.05). The diagnostic performance, indicated by the area under the curve (AUC), for PLT and PCT in diagnosing CMPA was 0.811 and 0.823, respectively. The cutoff values for PLT and PCT were determined to be 304.5×109/L and 0.305, respectively. 【Conclusion】 The PLT and PCT levels in children with CMPA are found to be higher than those in healthy controls, suggesting their potential diagnostic value in the diagnosis of CMPA.
10.circRAF1 regulates the proliferation and apoptosis of human ovarian granulosa cells
Wenxin LI ; Minjun LU ; Li LIN ; Yueqin LIU ; Xiaolan ZHU
The Journal of Practical Medicine 2024;40(7):910-917,923
Objective To investigate the expression of circRAF1 in primary ovarian insufficiency(POI)and explore its effect on cell proliferation and apoptosis of human ovarian granulosa cells(GCs)line(KGN cells).Methods The expression of circRAF1 in GCs and serum of patients with normal ovarian reserve function(n = 50)and patients with POI(n = 50)were detected with RT-qPCR.The correlation of circRAF1 with ovarian reserve function indexes was analyzed.Small interfering RNA(siRNA)targeting circRAF1 was constructed and trans-fected into KGN cells,with the cell proliferation detected by CCK-8 and EdU assay,and the cell apoptosis detected by JC-1 and Tunel assay.The mRNA and protein levels of genes related to cell proliferation and apoptosis(FSHR,PCNA,Bcl-2,Casp-9,Bax)were detected by RT-qPCR and WB.Results The expression of circRAF1 decreased in GCs and serum of POI patients.The expression of circRAF1 was positively correlated with serum E2 and AMH levels(P<0.001),but negatively correlated with serum FSH and LH levels(P<0.001).At the same time,the expression of circRAF1 was positively correlated with AFC(P<0.001).Interfering with the expression of circRAF1 could inhibit the proliferation of KGN cells and promote their apoptosis.Conclusion The expression of circRAF1 in the GCs and serum of POI patients is down-regulated,which is correlated with the decline of ovarian reserve function.Interfering with circRAF1 can inhibit the proliferation of GCs and promote their apoptosis.


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