1.Untargeted Metabolomics Reveals Mechanism of Modified Sinisan in Ameliorating Anxiety-like Behaviors Induced by Chronic Restraint Stress in Mice
Jie ZHAO ; Zhengyu FANG ; He XIAO ; Na GUO ; Hongwei WU ; Hongjun YANG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(21):70-79
ObjectiveTo elucidate the potential mechanism of modified Sinisan (MSNS) in alleviating anxiety-like behaviors induced by chronic restraint stress (CRS) in mice at the metabolic level based on serum untargeted metabolomics and identify key metabolites and metabolic pathways regulated by MSNS. MethodsSeventy-two male C57BL/6 mice were randomly assigned into six groups: control, model, high-dose (2.4 g·kg-1) MSNS, medium-dose (1.2 g·kg-1) MSNS, low-dose (0.6 g·kg-1) MSNS, and positive control (fluoxetine, 2.6 mg·kg-1). Except the control group, the other groups were subjected to CRS for the modeling of anxiety. Mice were administrated with corresponding agents by gavage 2 h before daily restraint for 14 days. Anxiety-like behaviors were evaluated by the open field test (OFT), elevated plus maze (EPM) test, and light/dark box (LDB) test. Serum levels of corticotropin-releasing hormone (CRH), adrenocorticotrophic hormone (ACTH), and corticosterone (CORT) were measured via ELISA to assess stress levels. Ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was employed to detect 9 metabolites in the brain tissue and serum metabolites. Orthogonal partial least squares-discriminant analysis (OPLS-DA) was adopted to identify differential metabolites (VIP>1.0, P<0.05). MetaboAnalyst 5.0 was used for metabolic pathway enrichment analysis of the differential metabolites. ResultsCompared with the control group, the model group showed reductions in the central activity time and central distance in the OFT (P<0.05), the proportions of open-arm residence time and open-arm residence times in the EPM test (P<0.01), and the proportions of open box activity time and open box activity distance in the LDB test (P<0.05), which were increased in the medium- and high-dose MSNS groups compared with the model group (P<0.05). Compared with the control group, the model group showed elevated levels of CRH, ACTH, and CORT in the serum (P<0.01), and the elevations were diminished in the medium- and high-dose MSNS groups (P<0.05). UPLC-MS results indicated that compared with the control group, the model group presented declined DA, GABA, 5-HIAA, 5-HT, and 5-HT/Trp levels (P<0.05, P<0.01) and raised Glu, NE, Kyn, and Kyn/Trp levels (P<0.05). Compared with the model group, high-dose MSNS increased the GABA, 5-HIAA, and 5-HT/Trp levels (P<0.05) and lowered the Glu and Kyn/Trp levels (P<0.05). Untargeted metabolomics identified that 16 CRS-induced metabolic disturbances were reversed by MSNS. KEGG pathway analysis indicated that MSNS primarily modulated eight core pathways including alanine/aspartate/glutamate metabolism, butyrate metabolism, arginine-proline metabolism, TCA cycle, unsaturated fatty acid biosynthesis, and tryptophan metabolism. The mechanisms involved multidimensional biological processes, including neurotransmitter homeostasis regulation, TCA cycle energy metabolism optimization, and inflammatory response suppression. ConclusionMSNS alleviates CRS-induced anxiety-like behaviors in mice by mitigating hypothalamic-pituitary-adrenal axis hyperactivity, improving hippocampal neurotransmitter and tryptophan metabolic pathways, and regulating alanine/aspartate/glutamate metabolism, butyrate metabolism, arginine-proline metabolism, and TCA cycle.
2.Untargeted Metabolomics Reveals Mechanism of Modified Sinisan in Ameliorating Anxiety-like Behaviors Induced by Chronic Restraint Stress in Mice
Jie ZHAO ; Zhengyu FANG ; He XIAO ; Na GUO ; Hongwei WU ; Hongjun YANG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(21):70-79
ObjectiveTo elucidate the potential mechanism of modified Sinisan (MSNS) in alleviating anxiety-like behaviors induced by chronic restraint stress (CRS) in mice at the metabolic level based on serum untargeted metabolomics and identify key metabolites and metabolic pathways regulated by MSNS. MethodsSeventy-two male C57BL/6 mice were randomly assigned into six groups: control, model, high-dose (2.4 g·kg-1) MSNS, medium-dose (1.2 g·kg-1) MSNS, low-dose (0.6 g·kg-1) MSNS, and positive control (fluoxetine, 2.6 mg·kg-1). Except the control group, the other groups were subjected to CRS for the modeling of anxiety. Mice were administrated with corresponding agents by gavage 2 h before daily restraint for 14 days. Anxiety-like behaviors were evaluated by the open field test (OFT), elevated plus maze (EPM) test, and light/dark box (LDB) test. Serum levels of corticotropin-releasing hormone (CRH), adrenocorticotrophic hormone (ACTH), and corticosterone (CORT) were measured via ELISA to assess stress levels. Ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was employed to detect 9 metabolites in the brain tissue and serum metabolites. Orthogonal partial least squares-discriminant analysis (OPLS-DA) was adopted to identify differential metabolites (VIP>1.0, P<0.05). MetaboAnalyst 5.0 was used for metabolic pathway enrichment analysis of the differential metabolites. ResultsCompared with the control group, the model group showed reductions in the central activity time and central distance in the OFT (P<0.05), the proportions of open-arm residence time and open-arm residence times in the EPM test (P<0.01), and the proportions of open box activity time and open box activity distance in the LDB test (P<0.05), which were increased in the medium- and high-dose MSNS groups compared with the model group (P<0.05). Compared with the control group, the model group showed elevated levels of CRH, ACTH, and CORT in the serum (P<0.01), and the elevations were diminished in the medium- and high-dose MSNS groups (P<0.05). UPLC-MS results indicated that compared with the control group, the model group presented declined DA, GABA, 5-HIAA, 5-HT, and 5-HT/Trp levels (P<0.05, P<0.01) and raised Glu, NE, Kyn, and Kyn/Trp levels (P<0.05). Compared with the model group, high-dose MSNS increased the GABA, 5-HIAA, and 5-HT/Trp levels (P<0.05) and lowered the Glu and Kyn/Trp levels (P<0.05). Untargeted metabolomics identified that 16 CRS-induced metabolic disturbances were reversed by MSNS. KEGG pathway analysis indicated that MSNS primarily modulated eight core pathways including alanine/aspartate/glutamate metabolism, butyrate metabolism, arginine-proline metabolism, TCA cycle, unsaturated fatty acid biosynthesis, and tryptophan metabolism. The mechanisms involved multidimensional biological processes, including neurotransmitter homeostasis regulation, TCA cycle energy metabolism optimization, and inflammatory response suppression. ConclusionMSNS alleviates CRS-induced anxiety-like behaviors in mice by mitigating hypothalamic-pituitary-adrenal axis hyperactivity, improving hippocampal neurotransmitter and tryptophan metabolic pathways, and regulating alanine/aspartate/glutamate metabolism, butyrate metabolism, arginine-proline metabolism, and TCA cycle.
3.Occurrence of hyperactivity behavior and its relationship with neuropsychological development in children aged 3-6 in Yunnan Province
Chinese Journal of School Health 2024;45(8):1106-1110
Objective:
To investigate the prevalence of hyperactivity behavior in children aged 3-6 in Yunnan Province, to explore its relationship with neuropsychological development, so as to provide clues for early prevention and intervention of attention deficit hyperactivity disorder (ADHD) in children.
Methods:
A total of 1 321 children aged 3 to 6 from 10 kindergartens in 5 prefectures (cities) of Yunnan Province were selected by stratified random sampling method from October 2022 to May 2023. Teacher Rating Scale (TRS) was used to investigate childrens hyperactive behavior and coexistent behavior. A qualified evaluator applied the Developmental Scale for Children Aged 0-6 Years to assess the development of 5 ability areas of gross motor movement,fine movement,adaptive ability,language and social behavior. Statistical analysis was performed using Wilcoxon rank sum test and χ2 test. Binary Logistic regression was applied to analyze the score of their hyperactivity behavior and its relationship with other behavior problems and neuropsychological development.
Results:
The detection rate of hyperactivity behavior was 8.6% in children aged 3 to 6 years, 12.8% in boys and 4.1% in girls (χ2=31.53, P<0.01). The detection rate of hyperactivity in 3yearold children was 13.9%, which was higher than that in 4yearold (9.2%) and 5yearold children (7.0%) (χ2=8.73, P<0.05). The detection rate of inattentionpassivity of rural children (14.6%) was higher than that of urban children (5.9%) (χ2=22.23, P<0.01). Binary Logistic regression analysis showed that the higher the level of adaptive development, the lower the risk of hyperactivity (OR=0.58, 95%CI=0.39-0.86), the higher the risk of hyperactivity (OR=0.57, 95%CI=0.35-0.91), the higher the risk of conduct problems (OR=0.57, 95%CI=0.37-0.87), inattentionpassivity (OR=0.49, 95%CI=0.33-0.74) were also at lower risk (P<0.05). Children with higher levels of fine motor development had a lower risk of inattentionpassivity (OR=0.59, 95%CI=0.37-0.93, P<0.05).
Conclusions
Hyperactivity in boys and inattentionpassivity in rural children requires more attention. It is necessary to strengthen childrens early adaptive ability and fine motor training to prevent hyperactive behavior and inattention.
4.Short-term results of sleeve wrapping technique using remnant aortic wall in modified Bentall procedure
MENG Maolong ; Yao WANG ; Pingfan LU ; Huapeng LI ; Rong REN ; Wen ZHANG ; Fengjie CHEN ; Xianmian ZHUANG ; Xiang WANG ; Gang LI ; Hongwei GUO
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2024;31(02):283-287
Objective To evaluate the short-term results of sleeve wrapping technique using remnant aortic wall in modified Bentall procedure. Methods The patients undergoing modified Bentall procedure with the remnant aortic wall as a sleeve to cover the sewing area of composite valved graft and the aortic annulus for proximal hemostasis between March 2021 and March 2022 in Shenzhen Fuwai Hospital were enrolled. Short-term results were assessed by cardiopulmonary bypass time, aortic clamping time, mechanical ventilation time, ICU stay, postoperative hospital stay, effusion drainage on the first postoperative day, left ventricular ejection fraction (LVEF), left ventricular end diastolic diameter (LVEDD), and follow-up results. Results A total of 14 patients were collected, including 12 males and 2 females, with a mean age of 55.33±10.57 years. There was no postoperative or follow-up death. Cardiopulmonary bypass time was 147.90±21.29 min, aortic clamping time was 115.70±15.23 min, mechanical ventilation time was 19.42±8.98 h, ICU stay was 99.08±49.42 h, and postoperative hospital stay was 16.33±2.74 d. Thoracic drainage volume was 333.33±91.98 mL on the first postoperative day. Only 2 patients required blood transfusion (4.5 U and 2 U, respectively). During the follow-up of 6.17±3.69 months, there was no death, no aortic or valve-related complications. There was statistical difference in the LVEDD between preoperation and before discharge after surgery (P<0.001), and between half a year after surgery and before discharge after surgery (P<0.001). There was a little decrease of LVEF before discharge after surgery compared with preoperative LVEF, but there was no statistical difference (P=0.219). There was no statistical difference in the LVEF half a year after operation compared with that before operation (P=1.000). Conclusion Sleeve wrapping technique using remnant aortic wall in modified Bentall procedure has good short-term results. This modification may be a simple, effective way in controlling proximal bleeding.
5.Research progress on aortic root repair by modified sandwich technique for acute Stanford type A aortic dissection
Chuang LIU ; Shuya FAN ; Yangxue SUN ; Hongwei GUO
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2024;31(03):478-484
Acute Stanford type A aortic dissection has the characteristics of acute onset, severe condition and high mortality. Once making a definite diagnosis, surgical treatment is needed as soon as possible. It is difficult for cardiac surgeons to treat the acute aortic dissection involving the aortic sinus, which is an important risk factor for death. Improving the surgical treatment for the aortic sinus can be a key to improving the prognosis. In this review, we will introduce the modified sandwich technique for acute Stanford type A aortic dissection and the prognosis, and summarize the experiences of different modified sandwich techniques. However, there is still no unified standardized technique in aortic root repair, and there is a lack of large studies with long-term follow-up, so it is necessary to further improve the aortic root repair techniques.
6.Urogenital solitary fibrous tumor: a review of 20 cases
Hongwei SHEN ; Bo JIANG ; Xin WANG ; Changwei JI ; Yongming DENG ; Shiwei ZHANG ; Hongqian GUO
Journal of Modern Urology 2024;29(2):130-135
【Objective】 To explore the diagnosis, treatment, prognosis and long-term follow-up of urogenital solitary fibrous tumor (SFT) and to differentiate the characteristics between benign and malignant SFT. 【Methods】 Clinical data of 20 patients with urogenital SFT treated in our hospital during Jan.2004 and Aug.2021 were respectively analyzed, including the general characteristics, clinical symptoms, imaging results, treatment methods, pathological results, and long-term follow-up results. 【Results】 Of the 20 cases, 9 cases had tumor in kidney, 7 in pelvic cavity, 3 in bladder and 1 in prostate.Six patients showed non-specific clinical symptoms, including lower extremity weakness, urodynia, dysuria, frequent urination with changes in stool habits, low back pain, and abdominal wall mass with abdominal pain, and the other 14 cases were asymptomatic.The median diameter of SFT was 5.2 cm (range:1.7-15.0 cm).All patients received surgical treatment, including robotic-assisted surgery in 8 cases, open surgery in 5 cases, laparoscopic surgery in 5 cases, and transurethral resection of tumor in 2 cases.CT plain scan showed high, low and mixed density soft tissue masses, and enhanced CT showed enhanced results.Pathology results revealed frequent nuclear divisions, morphological variations and necrosis in malignant SFT, which had higher expression of Ki-67 than benign SFT.The results of the modified Demicco prognostic risk stratification model showed that all malignant SFT cases were at intermediate risk. The DFS of the SFT radical tumor resection group was slightly longer than that of the simple tumor resection group but the difference was not statistically significant (P=0.203). 【Conclusion】 Markers such as CD34, Bcl2, STAT6 and CD99 are used to diagnose SFT, while Ki-67 and tumor necrosis are used to differentiate benign and malignant SFT.The modified Demicco prognostic risk stratification model plays an important role in predicting the prognosis of SFT.Surgical resection is the most common treatment with excellent prognosis.In addition, benign SFT has much better prognosis than malignant case.
7.Short-term efficacy analysis of platelet-rich plasma in arthroscopic rotator cuff repair by comparison of LP-PRP and LR-PRP
Pengshan WANG ; Xiaosong BAI ; Haoran SUN ; Haoxuan LI ; Hongwei CHAI ; Hao LIU ; Hao GUO ; Shuqin ZHU ; Xiaoxin SUN
The Journal of Practical Medicine 2024;40(19):2713-2719
Objective By comparing with arthroscopic rotator cuff repair alone,to explore the efficacy and difference of leukocyte poor platelet-rich plasma(LP-PRP)and leukocyte rich platelet-rich plasma(LR-PRP)in arthroscopic rotator cuff repair.Methods Sixty patients with total rotator cuff tear accompanied by arthroscopic rotator cuff repair admitted to the Affiliated Hospital of North China University of Science and Technology from October 2021 to September 2022 were included and randomly divided into control group(n=20),LP-PRP group(n=20)and LR-PRP group(n=20).The control group only received arthroscopic rotator cuff repair.The LP-PRP group was injected with leukocyte poor platelet-rich plasma(LP-PRP)into the sutured torn tendon after the same operation,and the LR-PRP group was injected with leukocyte rich platelet-rich plasma(LR-PRP)into the sutured torn tendon after the same operation.The postoperative rehabilitation training plan of the three groups was the same,and the postoperative follow-up and evaluation were conducted for 1 year.It included pain score(VAS score),shoulder joint function score(CMS,UCLA,ASES score),retear rate and related complications.Results All patients were followed up.(1)VAS score:Compared with the LR-PRP group and the control group,the results were statistically significant only at 1,3 and 6 weeks after surgery(P<0.05);There was no statistical significance between the LR-PRP group and the control group at 1 week,3 weeks,6 weeks,3 months,6 months and 12 months after surgery(P>0.05).(2)CMS,UCLA and ASES scores:There were no significant differences between the LP-PRP group and the LR-PRP group at 3 months,6 months and 12 months after surgery(P>0.05);Compared with LP-PRP group and LR-PRP group,there were significant differences in each follow-up time point of control group(P<0.05).(3)Retear rate:In the LP-PRP group,there was 1 retear in the LR-PRP group(tear rate 5%),and 3 in the control group(tear rate 15%).There was no statistically significant difference between the three groups(P>0.05).(4)There were no postoperative complications in 60 patients.Conclusions Compared with arthroscopic rotator cuff repair alone,although the application of LP-PRP and LR-PRP could not reduce the rate of retear,it could significantly improve the shoulder joint function of patients,and LP-PRP could significantly reduce the pain of patients with rotator cuff injury in the early postoperative period(within 6 weeks),with no postoperative complications,and the short-term clinical results of patients were satisfactory.
8.Biopsy pathological analysis of bladder mucosal red patch
Xin WANG ; Zhiyang WANG ; Huiyu CHEN ; Hongwei SHEN ; Shun ZHANG ; Qing ZHANG ; Yongming DENG ; Shiwei ZHANG ; Hongqian GUO
Journal of Modern Urology 2024;29(8):685-690
Objective To analyze the characteristics and malignancy of red-patch like lesion(RPL)during cystoscopy,and to explore the significance of RPL biopsy.Methods Clinical data of patients who had RPL detected in our hospital during Jan.2019 and Jun.2023 were retrospectively analyzed,including gender,age,cause of examination,presence of scars,complications and biopsy pathology.The patients were divided into the benign and malignant groups,and their clinical and RPL characteristics were analyzed.Results A total of 521 cases of RPL were enrolled including 416(79.8%)benign cases,and 105(20.2%)malignant cases.The averae age of the malignant group was higher than the benign group's[(66.8±12.2)years vs.(62.8±12.9)years,P=0.005].The malignant detection rate of RPL in postoperative follow-up patients,those with hematuria and those with lower urinary tract symptoms was 23.7%(92/389),19.6%(9/46),4.7%(4/86),respectively.According to direct observation and experience,the detection rate of pathological malignancy in the three groups of patients with high suspicion of RPL malignancy,mild suspicion of RPL malignancy and high probability of benign was 56.9%(37/65),37.0%(30/81)and 10.1%(38/375),respectively.Conclusion Once RPL is detected during cystoscopy,active biopsy should be performed.For elderly male patients undergoing postoperative follow-up,RPL biopsy is particularly important,especially when the lesion is located on or near the scar surface.
9.Early to mid-term clinical outcomes of aortic valve repair in patients with bicuspid aortic insufficiency
Jing SUN ; Shuai ZHANG ; Wenying KANG ; Yi CHANG ; Dong ZHAO ; Hongwei GUO ; Xiangyang QIAN ; Zhe ZHENG
Chinese Journal of Surgery 2024;62(5):393-399
Objective:To examine the early to mid-term clinical outcomes of aortic valve repair in patients with bicuspid aortic insufficiency.Methods:This is a retrospective cohort study. The clinical data of 124 patients with BAV insufficiency who underwent aortic valve repair from January 2017 to June 2023 in the Department of Cardiovascular Surgery at Fuwai Hospital were analyzed retrospectively. There were 117 males and 7 females with an age of (38.1±12.7) years (range: 14 to 65 years). Depending on whether the aortic sinus was replaced or not, surgical approaches were divided into valve sparing root replacement (reimplantation, remodeling, modified remodeling) and isolated aortic valve repair (annuloplasty, isolated aortic valve leaflet repair). Perioperative and follow-up data were collected. Kaplan-Meier method was used to plot the curves of survival rate, free recurrence rate of massive aortic valve insufficiency and free re-operation rate, and Log-rank test was used for comparison between groups.Results:Among the surgeries, there were 47 cases of reimplantation, 8 cases of remodeling, 8 cases of modified remodeling, 48 cases of aortic annuloplasty (external annuloplasty in 22 cases, CV-0 annuloplasty in 26 cases), and 13 cases of isolated leaflet repair. Leaflet plication was the most used leaflet repair technique, used in 103 patients. The cardiopulmonary bypass time was (133.7±56.9) minutes (range: 48 to 461 minutes), and aortic cross-clamp time was (103.8±47.8) minutes (range: 25 to 306 minutes), with no surgical mortality. All patients underwent outpatient or telephone follow-up. The cumulative follow-up time was 340.3 person-years and the mean follow-up time was ( M (IQR)) 34.0 (25.5) months (range: 3 to 76 months). The 5-year survival rate was 98.4%, the 5-year freedom from significant insufficiency rate was 93.4% and the 5-year freedom from aortic valve reoperation rate was 95.6%. The subgroup analysis revealed a significantly better freedom from the significant insufficiency rate in the aortic valve annular reduction group compared to the non-reduction group ( P<0.01). Conclusions:Aortic valve repair in patients with bicuspid aortic insufficiency could obtain steady early to mid-term outcomes. Aortic annuloplasty can reduce the risk of recurrent aortic valve insufficiency in patients undergoing aortic repair.
10.Early to mid-term clinical outcomes of aortic valve repair in patients with bicuspid aortic insufficiency
Jing SUN ; Shuai ZHANG ; Wenying KANG ; Yi CHANG ; Dong ZHAO ; Hongwei GUO ; Xiangyang QIAN ; Zhe ZHENG
Chinese Journal of Surgery 2024;62(5):393-399
Objective:To examine the early to mid-term clinical outcomes of aortic valve repair in patients with bicuspid aortic insufficiency.Methods:This is a retrospective cohort study. The clinical data of 124 patients with BAV insufficiency who underwent aortic valve repair from January 2017 to June 2023 in the Department of Cardiovascular Surgery at Fuwai Hospital were analyzed retrospectively. There were 117 males and 7 females with an age of (38.1±12.7) years (range: 14 to 65 years). Depending on whether the aortic sinus was replaced or not, surgical approaches were divided into valve sparing root replacement (reimplantation, remodeling, modified remodeling) and isolated aortic valve repair (annuloplasty, isolated aortic valve leaflet repair). Perioperative and follow-up data were collected. Kaplan-Meier method was used to plot the curves of survival rate, free recurrence rate of massive aortic valve insufficiency and free re-operation rate, and Log-rank test was used for comparison between groups.Results:Among the surgeries, there were 47 cases of reimplantation, 8 cases of remodeling, 8 cases of modified remodeling, 48 cases of aortic annuloplasty (external annuloplasty in 22 cases, CV-0 annuloplasty in 26 cases), and 13 cases of isolated leaflet repair. Leaflet plication was the most used leaflet repair technique, used in 103 patients. The cardiopulmonary bypass time was (133.7±56.9) minutes (range: 48 to 461 minutes), and aortic cross-clamp time was (103.8±47.8) minutes (range: 25 to 306 minutes), with no surgical mortality. All patients underwent outpatient or telephone follow-up. The cumulative follow-up time was 340.3 person-years and the mean follow-up time was ( M (IQR)) 34.0 (25.5) months (range: 3 to 76 months). The 5-year survival rate was 98.4%, the 5-year freedom from significant insufficiency rate was 93.4% and the 5-year freedom from aortic valve reoperation rate was 95.6%. The subgroup analysis revealed a significantly better freedom from the significant insufficiency rate in the aortic valve annular reduction group compared to the non-reduction group ( P<0.01). Conclusions:Aortic valve repair in patients with bicuspid aortic insufficiency could obtain steady early to mid-term outcomes. Aortic annuloplasty can reduce the risk of recurrent aortic valve insufficiency in patients undergoing aortic repair.


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