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.Advances in the clinical application and safety of bispecific antibodies for cancer therapy
Mengmeng LIN ; Xu LIN ; Yixuan WANG ; Danna JIANG ; Shanshan SHI ; Yangling LI
China Pharmacy 2025;36(19):2466-2472
Bispecific antibodies (BsAbs), as an important recent innovation in the field of tumor immunotherapy in recent years, can simultaneously or sequentially target different antigens or two different epitopes of the same antigen. Compared with traditional monoclonal antibodies, they can produce superior therapeutic effects. This article reviews the progress in clinical applications and safety research of BsAbs in cancer therapy, revealing that they (such as blinatumomab, glofitamab, teclistamab, amivantamab, etc.) exhibit significant therapeutic efficacy against hematological malignancies, lung cancer, cervical cancer, melanoma, and other cancers. For cytokine release syndrome (CRS) induced by BsAbs, prophylactic or pre-emptive medication is commonly administered in clinical practice; for neurotoxicity and infections triggered by BsAbs, clinical practice necessitates rigorous monitoring of patients’ vital signs and the provision of essential treatments. In addition, different BsAbs exhibit variations in escalation dose, infusion rate, storage duration, and equipment requirements. Therefore, strict adherence to the instructions in the drug package inserts is essential during clinical operations to ensure safety and therapeutic efficacy. In the future, more multicenter trials need to be conducted to validate the efficacy and safety of BsAbs across different tumor types and patient populations, and long-term follow-up data should be accumulated to optimize treatment cycles and dosage regimens.
3.Comparison of clinical outcome between the percutaneous pedicle screw fixation and Wiltse approach for the treatment of thoracolumbar fractures without neurological injury
Mengmeng CHEN ; Pu JIA ; Hao CHEN ; Li BAO ; Guan SHI ; Fei FENG ; Shuangjiang ZHANG ; Hai TANG
International Journal of Surgery 2024;51(3):159-165
Objective:To compare the safety and efficacy of two different minimally invasive approaches to implant pedicle screw for the treatment of single-segment thoracolumbar spine fractures without nerve injury.Methods:This was a retrospective study. Eighty patients with mono-segmental thoracolumbar fractures treated with minimally invasive pedicle screw fixation at Beijing Friendship Hospital, Capital Medical University from January 2020 to June 2022 were included. There were 46 males and 36 females, the age was (45.93±7.91) years old, and ranged from 27 to 60 years old. They were divided into two groups according to different surgical techniques: percutaneous pedicle screw fixation group ( n=44) and Wiltse approach group ( n=36). The operative time, operative visible blood loss, hidden blood loss, total blood loss, fluoroscopy times, incision length, hospital time after surgery and ambulation time were compared. Visual analogue scale (VAS), Oswestry disability index (ODI), ratio of the vertebral anterior height, angle of injured vertebral endplate were recorded and compared between two groups before surgery and at 3 days, 6 months and 1 year after surgery. The accuracy of pedicle screw position and the facet joint violation rate were evaluated by using the postoperative CT scan. Perioperative related complications were investigated. Normally distributed numerical data were presented as mean ± standard deviation, and differences between the groups were compared using t-test. The counting data were expressed as percentages or rates and compared using χ2 test. Results:All patients were followed for a minimum of 12 months. There is no significant difference between the two groups in intraoperative visible blood loss, hospital time after surgery, ambulation time, postoperative VAS and ODI, ratio of vertebral anterior height and angle of injured vertebral endplate at 3 days after surgery, pedicle screw position accuracy and perioperative complications ( P>0.05). The operative time, hidden blood loss, total blood loss, intraoperative fluoroscopy times, facet joint violation rate in the percutaneous pedicle screw fixation group were remarkably higher than in the Wiltse approach group ( P<0.05). The ratio of vertebral anterior height in the percutaneous pedicle screw fixation group was dramatically lower than in the Wiltse approach group at 6 months and 1 year after surgery ( P<0.05). The postoperative injured vertebral endplate angle was higher in the percutaneous pedicle screw fixation group than that in the Wiltse approach group at 6 months and 1 year ( P<0.05). Conclusions:Both percutaneous pedicle screw fixation and Wiltse approach were safe and effective minimally invasive surgical procedures for the treatment of thoracolumbar fractures without neurological injury. The Wiltse approach can reduce fluoroscopy times and perioperative hidden blood loss, reduce the risk of facet joint violation, and maintain a better reduction than percutaneous pedicle screw fixation.
4.Biomechanical characteristics of a novel interspinous distraction fusion device BacFuse for the repair of lumbar degenerative disease
Mengmeng CHEN ; Li BAO ; Hao CHEN ; Pu JIA ; Fei FENG ; Guan SHI ; Hai TANG
Chinese Journal of Tissue Engineering Research 2024;28(9):1325-1329
BACKGROUND:Interspinous distraction fusion device BacFuse was used for the management of lumbar degenerative disease and obtained good clinical efficacy in recent years.However,the related biomechanical study was lacking. OBJECTIVE:To explore the related biomechanical characteristics of BacFuse,a novel interspinous distraction fusion device,which was used in lumbar degenerative disease. METHODS:After constructing the goat spinal models(L1-L6),they were grouped into four groups based on different simulated surgeries:the control group,the BacFuse group(L3/4),the screw-rod fixation group(L3/4)and the Topping-off group(L3/4 screw-rod fixation + L2/3 BacFuse fixation).The goat lumbar spine surgical model was assembled into a biomechanical testing system.A biomechanical machine was used for mechanical loading,simulating lumbar spine movement of flexion,extension,lateral flexion and rotation with a 4 Nm moment.A visual tracking system was used for positioning and capturing.Finally,mechanical and optical calibration was completed to calculate the range of motion of the L2/3,L3/4 and L4/5 segments. RESULTS AND CONCLUSION:(1)Compared with the control group,the range of motion of the L3/4 segment in the BacFuse group decreased 27.27%,70%,38.1%and 23.08%in the flexion,extension,lateral bending and rotation directions,respectively(P<0.05).The range of motion of L3/4 segment in the screw-rod fixation group decreased 72.73%,80%,71.43%and 73.08%in the flexion,extension,lateral bending and rotation directions,respectively(P<0.05).(2)Compared with the control group,the range of motion of the adjacent segment L2/3 increased by 33.33%,25%and 23.81%in the extension,lateral bending and rotation directions,respectively in the BacFuse group(P<0.05),with no significant change in flexion.In the screw-rod fixation group,there was a 50%,44.44%,50%and 58.96%increase in the adjacent segment L2/3 in the flexion,extension,lateral calibration and rotation directions,respectively(P<0.05).(3)Compared with the control group,the BacFuse group showed an increase in range of motion in proximal segment L4/5 in the extension and rotation directions by 27.3%and 17.39%(P<0.05)respectively,with no significant change in flexion or lateral bending.In the screw-rob fixation group,the proximal segment L4/5 demonstrated 38.89%,22.73%and 26.09%(P<0.05)increases in range of motion in the flexion,extension and rotation directions,respectively,with no significant change in lateral bending.(4)In the Topping-off group,the range of motion of L2/3 was reduced by 37.04%,73.08%,56.67%and 38.46%in flexion,extension,lateral flexion and rotation,respectively,compared to the screw-rob fixation group(P<0.05).Compared with the screw-rob fixation group,the Topping-off group showed a 20%reduction in the range of motion of the L4/5 in the flexion direction(P<0.05),with no significant differences seen in extension,lateral bending and rotation.(5)It is concluded that the interspinous distraction fusion device BacFuse significantly reduces the range of motion of the implanted segment and provides some stability.It still retains more mobility and reduces the impact on the adjacent segment compared to screw-rob fixation,while the Topping-off tip,which can be used for intervertebral fusion fixation,significantly reduces the range of motion of the adjacent segment and reduces the risk of adjacent segment degeneration.
5.Textual Analysis of Classical Prescription Yangweitang Based on Ancient Literature
Lyuyuan LIANG ; Jialei CAO ; Yiping WANG ; Mengmeng GENG ; Lujun ZHU ; Wenxin WEI ; Bingqi WEI ; Wenli SHI ; Bingxiang MA
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(12):147-157
The classical prescription Yangweitang, derived from Zhengzhi Zhunsheng, is specialized in treating syndromes of chill and fever due to exogenous pathogens, inner-cooling, and malaria, and it has been included in the Catalogue of Ancient Classical Formulas (the First Batch) published by the National Administration of Traditional Chinese Medicine (TCM) in 2018. Through bibliographical research, the relevant ancient books and modern documents were systematically sorted out, and it was found that there were many prescriptions related to the Yangweitang from Zhengzhi Zhunsheng. They were interwoven with Yangweitang from Zhengzhi Zhunsheng and widely used in clinical practice. In order to clarify their history and evolution, this paper combed the historical origin of Yangweitang and its related prescriptions and conducted textual analysis on key information such as semantic composition, herb origin, processing method, and efficacy. A total of 896 pieces of data on Yangweitang from Zhengzhi Zhunsheng were collected. 26 pieces of effective data were included after the screening, involving 17 ancient TCM books. Then, a total of 28 pieces of data on prescriptions related to the Yangweitang from Zhengzhi Zhunsheng were included, involving 23 ancient TCM books for reference. The textual analysis showed that Yangweitang originated from the Renshen Yangweitang recorded in Taiping Huimin Heji Jufang in the Song dynasty. Based on the original formula, medical experts from later generations have modified it into many different versions. A comparative analysis showed that Yangweitang from different generations had similar compositions, and the herb origin and processing method were basically clear. The recommended prescriptions are as follows: 37.3 g of Pinelliae Rhizoma Praeparatum Cum Alumine, Magnoliae Officinalis Cortex(fried with ginger juice), and frying with rice water Atractlodis Rhizoma, 27.98 g of Citri Exocarpium Rubrum, 18.65 g of Pogostemon cablin leaf, Tsaoko Fructus, Poria, and Ginseng Radix et Rhizoma, and 9.33 g of Glycyrrhizae Radix et Rhizoma. They could be ground into a coarse powder, with 14.92 g for every dose, and they could be orally taken after being decocted with 450 mL of water, 7 g of fresh ginger, and 2 g of Mume Fructus to 270 mL in warm conditions. Yangweitang from Zhengzhi Zhunsheng has the effect of warming the middle and releasing the external, and it can treat many syndromes including spleen and stomach disharmony caused by chill and fever due to exogenous pathogens and inner-cooling, as well as all kinds of malaria. Modern clinical applications mainly focus on chronic atrophic gastritis and other digestive system diseases.
6.Research progress on the clinical application of HIV integrase inhibitors
Yi ZHANG ; Bing SONG ; Yanze SHI ; Minrui YU ; Xin GUO ; Mengmeng QU ; Yanmei JIAO ; Fusheng WANG
Chinese Journal of Experimental and Clinical Virology 2024;38(2):202-208
Integrase inhibitors (INSTIs) are the newest class of antiretroviral drug which are available to people living with the human immunodeficiency virus (HIV). Since 2007, five types of INSTIs have been marketed: Raltegravir, Elvitegravir, Dolutegravir, Bictegravir and Cabotegravir, all of which were approved by the US Food and Drug Administration (FDA) for use in the initiation of antiretroviral therapy (ART) in treatment-na?ve individuals. Compared with other types of antiretroviral drugs, INSTIs have better efficacy and tolerability, so many countries around the world have listed INSTIs-containing regimens as the preferred regimen for HIV ART. In recent years, with the widespread use of INSTIs, some research data suggest that INSTIs may have some adverse effects (AEs), such as central nervous system symptoms, abnormal lipid metabolism, weight gain, abnormal liver and kidney function, etc. This review summarizes the current use of INSTIs in people living with the HIV, and highlights the clinical efficacy and their AEs among the five types of INSTIs in China.
7.Analysis of risk factors for unsatisfactory early pain relief after percutaneous vertebroplasty
Haibo SUN ; Shuangjiang ZHANG ; Guan SHI ; Mengmeng CHEN ; Hai TANG
International Journal of Surgery 2024;51(6):393-399
Objective:To investigate the risk factors for unsatisfactory early pain relief after percutaneous vertebroplasty (PVP).Methods:This was a retrospective cohort study, included 208 patients with osteoporotic vertebral compression fracture admitted to Beijing Friendship Hospital, Capital Medical University from January 2019 to March 2020. According to the early pain relief after PVP, they were divided into good pain relief group ( n=188) and poor pain relief group ( n=20). Influence factors were record and compare, including the gender, age, preoperative lumbar bone density, body mass index, number of fractured vertebral bodies, degree of fracture compression, operation time, bone cement leakage, bone cement dispersion, thoracolumbar fascia injury, sarcopenia, and Hospital Anxiety and Depression Scale (HADS) score and visual analogue score of pain between the two groups. Measurement data were expressed as mean ± standard deviation ( ± s), and independent samples t-test was used for comparison between groups; the Chi-square was used for comparison of count data between groups. Univariate and multivariate Logistic regression analysis were used to investigate the independent risk factors for poor early pain relief after PVP. Results:All patients underwent surgery successfully, without serious complications such as cement embolism, cardio-cerebrovascular accident, epidural hematoma, spinal cord and nerve injury. There were no significant differences in operation time, bone cement leakage and bone cement diffusion between the two groups ( P>0.05). The statistical results showed that compared with the good pain relief group, the patients with poor pain relief group had lower preoperative lumbar bone density ( t=2.35, P=0.020), higher proportion of thoracolumbar fascial injury ( χ2=8.66, P=0.003) and sarcopenia( χ2=7.15, P=0.007), higher preoperative HADS score ( t=2.51, P=0.013). Univariate and multivariate Logistic regression analysis showed that lower preoperative bone density, higher preoperative HADS score, and higher proportion of thoracolumbar fascia injury and sarcopenia were independent influencing factors for poor early pain relief after PVP. Conclusions:The poor early pain relief after PVP is associated with lower preoperative lumbar bone density, preoperative complications such as thoracolumbar fascial injury, sarcopenia, and preoperative anxiety. Effective prevention of the above factors should be taken during the perioperative period to avoid serious complications.
8.Preliminary biomechanical analysis and histological evaluation of fusion capacity after the implantation of interspinous distraction fusion device
Li BAO ; Mengmeng CHEN ; Hao CHEN ; Pu JIA ; Fei FENG ; Guan SHI ; Hai TANG
International Journal of Surgery 2024;51(7):476-481
Objective:To explore interspinous fusion capacity after interspinous distraction fusion (ISDF) device implantation, a preliminary biomechanical analysis and histological evaluation were performed.Methods:The experimental animals were procured from the Science and Research Laboratory Animal Center of Beijing Friendship Hospital, Capital Medical University. The animals were 8-9 weeks old and with an average weight of 25 kg. 15 mini-pigs were randomly divided into three groups, the sham operation group, the decompression group and the ISDF fixed decompression group, 5 animals per group. The sham operation group was treated with simple incision and exposed lamina suture. The decompression group received unilateral decompression and the ISDF fixed decompression group experienced unilateral hemilaminectomy decompression and ISDF fixation. The graft-bed site was filled with purified bone graft material without any autograft bone. After 6 months feeding, all experimental animals were sacrificed and the corresponding lumbar vertebrae was obtained. The samples were fixed on the spinal test system and the range of motion of flexion-extension, lateral bending and rotation were tested through a multiaxial robotic system. The ISDF device samples were embedded for hard tissue sections and stained with hematoxylin-eosin and toluidine blue to assess new bone formation. Normally distributed measurement data were expressed as mean±standard deviation( ± s), and independent samples t-test were used for comparisons between groups. Results:In comparison to the sham operation group, the decompression group exhibited a statistically significant increase in intervertebral mobility, with an average of 61.6% in anterior flexion, 44.7% in posterior extension, 65.0% in left lateral flexion, 49.6% in right lateral flexion, 83.8% in left rotation, and 64.2% in right rotation ( P<0.05). In comparison to the decompression group, the ISDF fixed decompression group exhibited a statistically significant decrease in intervertebral mobility, with an average of 40.0% in anterior flexion, 21.3% in posterior extension, 31.7% in left lateral flexion, 22.3% in right lateral flexion, 28.7% in left rotation, and 35.3% in right rotation ( P<0.05). Well-defined bone tissue can be observed in the histological images of ISDF fixed decompression group samples after 6 months. In the histological part, toluidine blue staining showed extensive new bone formation. The hyperchromatic osteoblasts cells and density bone tissue can be observed in hematoxylin-eosin staining slides. Conclusions:The implantation of ISDF provide the necessary stabilization for promoting fusion. The osteogenesis that occurs within graft-bed site of the ISDF device offers the possibility of interspinous fusion.
9.Diagnostic value of biparametric MRI radiomics in Gleason classification of prostate cancer
Lulu LIU ; Feng XU ; Mengmeng ZHU ; Chaomin CEN ; Jinfeng SHI ; Rui WANG ; Qianyu WANG
Journal of Practical Radiology 2024;40(7):1121-1124
Objective To explore the value of biparametric magnetic resonance imaging(bp-MRI)radiomics models in noninvasive prediction of high-risk prostate cancer.Methods A total of 320 patients with pathologically confirmed prostate cancer were retro-spectively selected,and all patients underwent bp-MRI before pathology,including T2WI and diffusion weighted imaging(DWI).Appar-ent diffusion coefficient(ADC)maps were extracted from DWI.All patients were divided into high-risk(Gleason score≥8)and medium-low risk(Gleason score ≤7)groups based on the Gleason score.Using 3D Slicer software,the entire prostate gland was outlined.Python software was used to calculate parameters,and the minimum redundancy maximum correlation and sequence back-ward elimination algorithms were used to extract and select radiomics features and to build a model.Three radiomics(T2 WI,DWI,ADC)models were constructed and verified by logistic regression(LR).The performance of the model was evaluated by area under the curve(AUC)of receiver operating characteristic(ROC)curve,specificity(SP),sensitivity(SE),and accuracy(ACC).An indi-vidual prediction model was established via the clinical data of 224 patients and bp-MRI features,and validated via the data of 96 patients.Results A total of 1 165 radiomics features were extracted.After feature screening,2,4 and 6 radiomics features were screened out to construct T2WI model,DWI model and ADC model for predicting high-risk prostate cancer.All radiomics models had significant predictive performance in identifying medium-low risk and high-risk groups(P<0.05).The DWI model had the highest predictive value,and the AUC,ACC,SE,and SP in the training group were 0.814,0.756,0.838,and 0.744,respectively.The AUC,ACC,SE,and SP in the verification group were 0.840,0.756,0.848,and 0.784,respectively.Conclusion Radiomics based on bp-MRI can better identify medium-low risk and high-risk prostate cancer before surgery.
10.Hemichorea associated with non-ketotic hyperglycemia and cerebral blood flow hypoperfusion
Xiaoxiao NIE ; Linlin CHAO ; Mengmeng CAI ; Jingjing SHI ; Jianhua ZHAO
Chinese Journal of Geriatric Heart Brain and Vessel Diseases 2024;26(9):1069-1072
Objective To analyze the clinical and imaging features of hemichorea associated with non-ketotic hyperglycemia(HC-NH)and to explore the perfusion of cerebral blood flow in the patients.Methods A retrospective study was conducted on 23 HC-NH patients diagnosed in Henan Provincial People's Hospital from January 2018 to December 2023.The clinical manifesta-tions,imaging features and prognosis were collected and analyzed,and the correlation with cere-bral blood flow hypoperfusion was investigated.Results The symptoms were all lateral involun-tary movements,of which 4 cases presented only single upper limb(1 case was left upper limb,the other 3 cases were right upper limb),and 19 cases had both upper and lower limbs involved(10 cases were left limb,and 9 cases were right limb).After the onset of the symptoms,the blood glucose level was 19.72±4.72 mmol/L,glycated hemoglobin level was(13.60±3.68)%,but all of patients were negative to urine ketone bodies.Hyperdense lesions in the contralateral basal ganglia region on CT images were observed in 6 cases.Strip or patchy hyperintensity was seen on T1-weighted MR images.All patients had ipsilateral stenosis of the vessels and regional hypoperfu-sion of cerebral blood flow as shown by MR perfusion-weighted imaging.All symptoms were re-lieved after actively controlling blood glucose,improving blood circulation,and symptomatic man-agement.Conclusion HC-NH is quite rare in clinical practice,and its occurrence may be related to cerebral blood flow hypoperfusion triggered by basal nucleus degeneration.

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