1.Mechanism of Wendantang in Intervention of ApoE-/- Hyperlipidemic Mice Based on Liver Metabolomics
Yun ZHOU ; Songren YU ; Lu ZHANG ; Wenting LIN ; Keming YU ; Min XIA ; Zhijun ZENG ; Yanhua JI
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(10):1-9
ObjectiveTo explore the mechanism of action of Wendantang on ApoE-/- hyperlipidemic mice using non-targeted metabolomics technology. MethodsMale C57BL/6J mice served as the normal control group (n=6), and they were fed with regular chow, while male ApoE-/- mice constituted the high-fat group (n=30), and they were fed with a 60% high-fat diet. After 11 weeks of model establishment, the mice in the high-fat group were randomly divided into the model group, simvastatin group (3.3 mg·kg-1), and high-dose, medium-dose, and low-dose groups of Wendantang (26, 13, 6.5 g·kg-1, respectively, in terms of crude drug amount), with six mice in each group. The normal control group and the model group were gavaged with an equivalent volume of normal saline, and all groups continued to be fed their respective diets, receiving daily medication for 10 weeks with weekly body weight measurements. Serum levels of total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), free fatty acids (NEFA), blood glucose (GLU), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) were detected in the mice. Pathological changes in liver tissue were observed using hematoxylin-eosin (HE) staining, and ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS/MS) was employed for metabolomic analysis of mouse liver tissue. ResultsCompared to the normal control group, the model group exhibited significantly increased body weight, blood lipid levels, and liver function (P<0.05, P<0.01), with disordered liver tissue structure, swollen hepatocytes, and accompanying vacuolar fatty degeneration and inflammatory cell infiltration. Compared to the model group, the simvastatin group and Wendantang groups showed significantly reduced body weight, TG, NEFA, GLU, ALT, and AST levels (P<0.05, P<0.01), with a significant increase in HDL-C levels (P<0.05, P<0.01), demonstrating a dose-dependent effect. The lesion of the liver tissue section was obviously improved after administration, tending towards a normal liver tissue morphology. Analysis of liver metabolites revealed 86 differential metabolites between the normal control group and the model group, with the high-dose group of Wendantang able to regulate 56 of these metabolites. Twenty-two differential metabolites associated with hyperlipidemia were identified, mainly including chenodeoxycholic acid, hyocholic acid, taurine, glycocholic acid, dihydroceramide, hydroxy sphingomyelin C14∶1, arachidonic acid, and linoleic acid, enriching 22 metabolic pathways, with 4 being the most significant (P<0.05), namely primary bile acid biosynthesis, sphingolipid metabolism, unsaturated fatty acid biosynthesis, and linoleic acid metabolism pathways. ConclusionWendantang can improve blood lipid levels and liver function in ApoE-/- hyperlipidemic mice, which may be related to the regulation of primary bile acid biosynthesis, sphingolipid metabolism, unsaturated fatty acid biosynthesis, and linoleic acid metabolism pathways.
2.Effect of Berberine-Baicalin Combination on Fecal Microbiota Transplantation-induced Type 2 Diabetes Mellitus Due to Internal Accumulation of Dampness-heat in Mice from Perspectives of Gut Microbiota and Metabolomics
Mengjie CHEN ; Yimin LIU ; Yun ZHOU ; Keming YU ; Min XIA ; Hongning LIU ; Yanhua JI ; Zhijun ZENG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(5):52-64
ObjectiveTo investigate the mechanisms by which the combination of berberine (BBR) and baicalin (BAI) ameliorates type 2 diabetes mellitus (T2DM) due to internal accumulation of dampness-heat from the perspectives of gut microbiota and metabolomics. MethodsAntibiotics were used to induce pseudo-sterile mice. Thirty pseudo-sterile mice were randomized into a normal fecal microbiota transplantation group (n=10) and a T2DM (syndrome of internal accumulation of dampness-heat) fecal microbiota transplantation group (n=20). The mice were then administrated with suspensions of fecal microbiota from healthy volunteers and a patient with T2DM due to internal accumulation of dampness-heat by gavage, respectively. Each mouse received 200 µL suspension every other day for a total of 15 times to reshape the gut microbiota. The T2DM model mice were then assigned into a model group (n=8) and a BBR-BAI group (n=11). BBR was administrated at a dose of 200 mg·kg-1, and BAI was administrated in a ratio of BBR-BAI 10∶1 based on preliminary research findings. The administration lasted for 8 consecutive weeks. Fasting blood glucose (FBG), glycated hemoglobin (HbA1c), insulin (INS), triglycerides (TG), total cholesterol (CHOL), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), aspartate aminotransferase (AST), and alanine aminotransferase (ALT) levels were measured to evaluate the effects of the BBR-BAI combination on glucose and lipid metabolism and liver function in T2DM mice. Hematoxylin-eosin staining was employed to observe pathological changes in the colon tissue. The expression of claudin-1, zonula occludens-1 (ZO-1), and occludin in the colon tissue was determined by Western blot. Real-time quantitative polymerase chain reaction(Real-time PCR) was employed to assess the levels of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6) in the colon tissue. The fecal microbiota composition and differential metabolites were analyzed by 16S rRNA sequencing and ultra-high performance liquid chromatography-quadrupole-time of flight tandem mass spectrometry (UPLC-Q-TOF-MS), respectively. ResultsThe BBR-BAI combination lowered the FBG, HbA1c, and INS levels (P<0.05, P<0.01) and alleviated insulin resistance (P<0.01) in T2DM mice. Additionally, BBR-BAI elevated the levels of ZO-1, occludin, and claudin-1 (P<0.05, P<0.01) and down-regulated the expression levels of TNF-α, IL-1β, and IL-6 in the colon (P<0.05, P<0.01). The results of 16S rRNA sequencing showed that BBR-BAI increased the relative abundance of Ligilactobacillus, Phascolarctobacterium, and Akkermansia (P<0.05), while significantly decreasing the relative abundance of Alistipes, Odoribacter, and Colidextribacter (P<0.05). UPLC-Q-TOF-MS identified 28 differential metabolites, which were primarily involved in arachidonic acid metabolism and α-linolenic acid metabolism. ConclusionBBR-BAI can ameliorate T2DM due to internal accumulation of dampness-heat by modulating the relative abundance of various bacterial genera in the gut microbiota and the expression of fecal metabolites.
3.Effect of Q Chromatography on the Recovery of Human Plasminogen in Affinity Chromatography
Shenglan YUE ; Taojing LI ; Juan LI ; Yan PENG ; Lianzhen LIN ; Yanxiang ZHOU ; Feifei WANG ; Chen ZHU ; Shang WANG ; Deming JI ; Shuangying ZENG ; Yong HU ; Zhijun ZHOU
Chinese Journal of Blood Transfusion 2025;38(10):1382-1388
Objective: To compare quality control (relative purity and specific activity) and process control [plasminogen (Pg) antigen recovery and potency recovery] indexes of samples before and after adding the Q chromatography step to the full chromatography process of human Pg, thereby determining whether the addition of this step could improve Pg recovery by affinity chromatography. Methods: A Q chromatography step was added before the Pg affinity chromatography in the original Pg chromatography process. The loading solution, flow through solution and eluate of Q chromatography and Pg affinity chromatography were collected. The potency of coagulation factor Ⅱ (FⅡ), Ⅶ (FⅦ), Ⅷ (FⅧ), Ⅸ (FⅨ), and Ⅹ(FⅩ) were detected by the coagulation method, the total protein content was detected by the BCA method, and the Pg potency was detected by the chromogenic substrate method. The content of specific plasma proteins was detected by immunoturbidimetry, the potency recovery of coagulation factors was calculated, and the flow direction of coagulation factors was analyzed. The recovery of different plasma protein antigens were calculated, and the distribution of impurity proteins was analyzed. The relative purity and specific activity of Pg, antigen content, and potency recovery in the target fractions were calculated and compared with the original process indicators, so as to determine the effect of adding Q chromatography on the original process. Furthermore, the reproducibility after process modification was assessed. Results: 100% of FⅡ, FⅩ, and FⅨ, 87.81% of FⅧ, and 40.44% of FⅦ in filtered plasma were removed by Q chromatography. The residual FⅦ (53.26%) and FⅧ (13.30%) in Q flow-through fraction were completely removed by Pg affinity chromatography. In both the original process (without Q-chromatography) and the modified process (with Q-chromatography), non-target plasma proteins mainly existed in the flow-through fraction of Pg affinity chromatography. The antigen recovery of IgM, ceruloplasmin (CER), and fibronectin (FNC) in Q-chromatography flow-through fraction were reduced. In contrast, antigen recovery of other plasma proteins [IgG, IgA, Pg, albumin (AlB), alpha-1-antitrypsin (AAT), and fibrinogen (Fg)] were all >90%, which were consistent with the protein composition and proportion in the original affinity chromatography loading solution. Compared with the recovery rate of Pg antigen in the original process (74.4%), the total recovery of Pg antigen in the modified process was significantly increased (89.97%). Compared with the recovery of IgG (97.48%) and Fg (95.32%) in the Pg affinity flows-through fraction of the original process, the modified process resulted in a slight reduction in the recovery of IgG (94.60%), while the recovery of Fg was not affected (95.05%). The potency recovery rate, specific activity, and relative purity of Pg after Q chromatography were 99.3%, 0.016 U/mg, and 0.15%. These values were the same as those of Pg affinity chromatography loading solution by the original process, indicating that introduction of Q chromatography did not affect subsequent Pg affinity chromatography. Compared with the recovery of Pg antigen in three batches of the original process (66.49±1.02)%, the recovery of Pg antigen in the affinity chromatography eluent of the modified process [five batches; (77.43±4.43)%] was significantly improved. Furthermore, the potency recovery was (86.80±4.28)%, the relative purity was (81.99±1.25)%, the specific activity was (8.679±1.073)U/mg, and the process was reproducible. Conclusion: The addition of Q chromatography could improve the recovery of Pg affinity chromatography in the full chromatography process.
4.Effect of lncRNA MIF-AS1 on the malignant biological behavior of prostate cancer cells by regulating the miR-423-5p/PYCR1 axis
Jianbo YANG ; Jichun SHAO ; Zhijun ZENG ; Tao ZHAO ; Xing WANG
The Journal of Practical Medicine 2024;40(18):2544-2549
Objective To investigate the effect of long non-coding RNA(lncRNA)macrophage migration inhibitory factor antisense RNA1(MIF-AS1)on the malignant biological behavior of prostate cancer(PC)cells by regulating the miR-423-5p/pyrroline-5-carboxylic acid reductase 1(PYCR1)axis.Methods PC3 cells were cultured in vitro to knock down the expression of MIF-AS1 or down-regulate the expression of miR-423-5p.The expression of MIF-AS1,miR-423-5p and PYCR1 mRNA in tumor tissues and adjacent tissues and cells of PC patients were detected.The cell proliferation,apoptosis,migration,and invasion were detected and the expression of PYCR1 protein was detected by Western blot.The relationships between miR-423-5p,IF-AS1 and PYCR1 were verified.Results The MIF-AS1 and PYCR1 mRNA were observed to be highly expressed in the tumor tissues,while miR-423-5p was lowly expressed.Silenced MIF-AS1 inhibited the proliferation,migration and invasion of PC3 cells and up-regulated miR-423-5p induced cell apoptosis(P<0.05).Inhibition of miR-423-5p expression reversed the inhibitory effect of silencing MIF-AS1 on malignant behavior of PC3 cells(P<0.05).miR-423-5p was correlated with MIF-AS1 and PYCR1 by targeted regulation.Conclusion Silencing MIF-AS1 may inhibit the expression of PYCR1 by up-regulating miR-423-5p,thereby inhibiting the malignant behavior of PC cells.
5.Handling health emergency in public hospitals
Zhijun LUO ; Dayue LIU ; Jiang CHEN ; Liangcheng XIAO ; Li'an LI ; Yuyao WANG ; Qingliang ZENG ; Qiusheng LIU
Modern Hospital 2024;24(2):293-296
Public hospitals play a dominant role in providing medical services.Meanwhile,they are also critical for un-dertaking missions to handle health emergencies.This paper analyzes the necessity,current situation,and existing weaknesses of the health emergency capacity of public hospitals.It also conducts a comparative study of the emergency response mechanisms of foreign medical institutions.This paper aims to explore a well-developed design for health emergency in public hospitals that is suitable for China's medical conditions and to provide a feasible model for promoting high-quality health emergency management.
6.Gegen Qinliantang and Its Modified Prescriptions Ameliorate Insulin Resistance in Type 2 Diabetes Mellitus: A Review
Yimin LIU ; Yanhua JI ; Mengjie CHEN ; Xiaojun YAN ; Hongning LIU ; Zhijun ZENG
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(15):256-263
Gegen Qinliantang is a representative prescription for dual releasing of exterior and interior and treating diarrhea with fever in the Treatise on Cold Damage and Miscellaneous Diseases (《伤寒杂病论》). This prescription consists of Puerariae Lobatae Radix, Scutellariae Radix, Coptidis Rhizoma, and Glycyrrhizae Radix et Rhizoma Praeparata cum Melle. The combination of the four herbal medicines has the ability to clear both the exterior and the interior, thereby halting diarrhea and clearing heat. According to the idea of treating different diseases with the same method, Gegen Qinliantang is used in clinical practice to treat type 2 diabetes mellitus (T2DM), which demonstrates positive outcomes. T2DM is a chronic metabolic disease characterized by elevated blood glucose levels. The etiology and pathogenesis of T2DM are complex, mainly related to heredity, lifestyle, environment, diet and other factors. Clinical observations and experimental studies have shown that Gegen Qinliantang and its effective ingredients have significant effects of preventing and treating T2DM. Clinically, Gegen Qinliantang is often applied with modification, or in combination with Western drugs, demonstrating better therapeutic effects than Western drugs alone. Clinical practice has confirmed that Gegen Qinliantang can effectively alleviate the clinical symptoms, reduce the occurrence of complications, and alleviate gastrointestinal adverse reactions in T2DM patients. Experimental studies have demonstrated that Gegen Qinliantang can ameliorate insulin resistance and boost pancreatic function by regulating the insulin and inflammation signaling pathways, alleviating oxidative stress, and modulating gut microbiota to treat T2DM. Nevertheless, more thorough studies remain to be carried out to decipher the mechanism of Gegen Qinliantang in ameliorating insulin resistance in T2DM. To provide theoretical and data references for the subsequent in-depth research on the mechanism of Gegen Qinliantang in treating T2DM and the prevention and treatment of this disease, this article systematically reviews the clinical and experimental research progress of Gegen Qinliantang in ameliorating insulin resistance in T2DM.
7.Heat-sensitive moxibustion combined with medication for orthostatic hypotension of yang-qi deficiency in the elderly: a randomized controlled trial.
Zhijun CHEN ; Meihua LIU ; Jun XIONG ; Jianguang WU ; Huaiyang HE ; Jianbin ZENG
Chinese Acupuncture & Moxibustion 2024;44(11):1245-1248
OBJECTIVE:
To observe the effect of heat-sensitive moxibustion combined with medication on orthostatic hypotension (OH) of yang -qi deficiency in the elderly.
METHODS:
Sixty elderly patients with OH of yang -qi deficiency were randomly divided into an observation group (30 cases, 1 case dropped out) and a control group (30 cases). The patients in the control group were treated with oral midodrine hydrochloride tablets, 2.5 mg each time and twice daily, while the patients in the observation group were treated with heat-sensitive moxibustion in addition to the treatment in the control group. Acupoints selected included Dazhui (GV 14), Fengfu (GV 16), and Baihui (GV 20), with each session lasting 30-40 min, once daily. Both groups were treated for 4 weeks. Blood pressure in the supine and standing positions, as well as the decrease of blood pressure when the position changing from supine to standing, were measured before treatment and after 2 and 4 weeks of treatment. Clinical efficacy was also evaluated.
RESULTS:
After 4 weeks of treatment, both groups showed an increase in systolic blood pressure (SBP) and diastolic blood pressure (DBP) in both the supine and standing positions (P<0.05), and the decrease in SBP and DBP when the position changing from supine to standing was reduced (P<0.05). Compared with the control group, the observation group had higher SBP and DBP in both positions and a smaller decrease in SBP and DBP when the position changing from supine to standing (P<0.05). The total effective rate was 96.6% (28/29) in the observation group, which was higher than 70.0% (21/30) in the control group (P<0.05).
CONCLUSION
Heat-sensitive moxibustion combined with medication could increase the blood pressure in both supine and standing position, and decrease the reducing of blood pressure when the position changing from supine to standing in elderly patients with OH of yang-qi deficiency.
Humans
;
Moxibustion
;
Hypotension, Orthostatic/etiology*
;
Male
;
Aged
;
Female
;
Combined Modality Therapy
;
Acupuncture Points
;
Yang Deficiency/therapy*
;
Blood Pressure/drug effects*
;
Aged, 80 and over
;
Middle Aged
;
Midodrine
8.Exploration of pharmaceutical service model in multidisciplinary diagnosis and treatment of rare diseases in children
Liang HUANG ; Qiqiong WANG ; Li CHEN ; Dan YU ; Jin WU ; Yunzhu LIN ; Linan ZENG ; Zhijun JIA ; Guo CHENG ; Lingli ZHANG
China Pharmacy 2023;34(8):1000-1004
OBJECTIVE To explore the pharmaceutical service model in multidisciplinary diagnosis and treatment (MDT) of rare diseases in children. METHODS Clinical pharmacists of West China Second University Hospital (hereinafter referred to as “our hospital”) participated in the process of MDT of children’s rare diseases. Clinical pharmacists took part in the entire diagnosis and treatment process of children and established the MDT pharmaceutical service model of children’s rare diseases by formulating drug treatment plans based on evidence-based practice, improving the accessibility of drugs, pharmaceutical monitoring and drug treatment management. RESULTS From January 2021 to April 2022, clinical pharmacists of our hospital had participated in a total of 39 cases of rare diseases MDT in children, including 21 hospitalized children with rare diseases and 18 outpatient com children with rare diseases, involving a total of 23 rare diseases. Clinical pharmacists completed 45 pharmaceutical zhanglingli@scu.edu.cn rounds and 26 pharmaceutical consultations for rare diseases inpatients, 25 outpatients’ MDT and 5 pharmaceutical outpatient service for outpatients with rare diseases, 38 medication educations for inpatients and outpatients with rare diseases and 25 follow-up services for out-of-hospital patients. There were 24 cases (61.54%) of off-label drug use, involving 13 rare diseases and 16 therapeutic drugs, among which off-label drug use registration of 11 drugs had been completed or was in progress. The temporary purchase evaluations of 3 drugs had been completed; 268 cases of medical insurance drug and high-value drug prescription had been reviewed. CONCLUSIONS Our hospital have primarily established a loop pharmaceutical service model of MDT for children with rare diseases, which covers inpatients and outpatients. The model improves the availability and standardization of clinical application of therapeutic drugs, and diagnosis and treatment level for children with rare diseases in our hospital.
9.Application value of single-port laparoscopic left lateral donor liver acquisition in pediatric living donor liver transplantation
Mingyue ZHU ; Lin WEI ; Hongyu LI ; Zhigui ZENG ; Wei QU ; Zhijun ZHU
Chinese Journal of Digestive Surgery 2023;22(2):268-273
Objective:To investigate the application value of single-port laparoscopic left lateral donor liver acquisition in pediatric living donor liver transplantation (PLDLT).Methods:The retrospective and descriptive study was conducted. The clinical data of the donor and recipient who were admitted to Beijing Friendship Hospital of Capital Medical University for PLDLT in January 2020 were collected. The donor was a male, aged 28 years with body mass as 62 kg, height as 174 cm and body mass index (BMI) as 20.5 kg/m 2. The recipient was the daughter of the donor, aged 1 year with body mass as 9 kg, height as 75 cm and BMI as 16.0 kg/m 2. The donor underwent single-port laparoscopic left lateral donor liver acquisition. The recipient underwent living donor liver trans-plantation by the same operation team. Observation indicators: (1) intraoperative conditions; (2) postoperative conditions; (3) follow-up. Results:(1) Intraoperative conditions. The donor under-went single-port laparoscopic left lateral donor liver acquisition successfully, with the single-port access system being placed through a transumbilical incision. The operation time, the warm ischemia time of the donor liver and volume of intraoperative blood loss were 240 minutes, 3 minutes and 40 mL, respectively, of the donor. The weight of the donor liver was 233.6 g, and the corrected graft-to-recipient body weight ratio was 2.60%. The recipient underwent living donor liver transplantation successfully. (2) Postoperative conditions. The donor began to take liquid diet at postoperative day 1, and results of laboratory examination showed that the alanine aminotransferase (ALT), aspartate aminotransferase (AST), glutamyltransferase (GGT) and total bilirubin (TBil) of the donor was 239 U/L, 116 U/L, 53 U/L and 22.57 μmol/L. The donor began to take diet with high quality proteins at postoperative day 2, and to get for out-of-bed activities moderately. The donor′s peritoneal drainage fluid was light red at postoperative day 3, and no fluid accumulation was found in the operation area after abdominal B-ultrasound examination, so the peritoneal drainage tube was removed. The donor was discharged at postoperative day 4. The liver function of the recipient recovered to normal level 2 weeks after the operation. (3) Follow-up. The donor was followed up by outpatient examination 2 weeks after discharged, and results of laboratory examination showed that the ALT, AST, GGT and TBil was 44 U/L, 25 U/L, 53 U/L and 9.22 μmol/L, respectively. Neither the donor nor the recipient had complication ≥Ⅱ grade of the Clavien-Dino classification, such as biliary fistula and vascular complication during the 6 months after operation.Conclusion:Single-port laparoscopic left lateral donor liver acquisition can be used into the PLDLT.
10.MiR-181a promotes the growth of chondrosarcoma cells by targeting PTEN
Pan HE ; Zhijun WANG ; Xukai ZENG
Journal of Chinese Physician 2023;25(4):541-545
Objective:To explore the effect of miR-181a on chondrosarcoma cell growth through phosphatase and tensin homolog(PTEN) and its possible regulatory mechanism.Methods:From January to December 2022, 10 fresh chondrosarcoma and 10 chondroma tissues from orthopedic patients of Hunan Provincial People′s Hospital were collected, and the expression of miR-181a in chondrosarcoma and chondroma tissues was detected using real-time fluorescence quantitative polymerase chain reaction (qRT-PCR); Chondrosarcoma cell SW1353 was cultured in vitro and transfected with miR-181a inhibitor (miR-181a inhibition group) and control (miR-NC, control group), respectively. The effects of miR-181a on the growth and proliferation of SW1353 cells were detected by cell counting kit (CCK-8) and clone formation test, respectively; The binding sites between miR-181a and PTEN were predicted through the Target Scan database, and verified using dual luciferase reporter gene experiments; The mimetic miR-181a (miR-181a group) and its control (miR-NC, control group) were transfected into chondrosarcoma cell SW1353, respectively. The adenosine triphosphate (ATP) content, glucose consumption, and lactic acid production in the cells were measured, and the effect of miR-181a on glycolysis of SW1353 cells was analyzed. Results:The expression of miR-181a in chondrosarcoma tissues was significantly higher than that in chondroma tissues ( P<0.05). The cell growth and clonogenesis ability of miR-181a inhibition group were significantly lower than those of control group (all P<0.05). It was predicted by Target Scan online website that there might be binding sites between miR-181a and PTEN, and co-transfection of wild-type PTEN and miR-181a could significantly reduce luciferase activity by double luciferase reporter assay ( P<0.05). The ATP content, glucose consumption and lactic acid production of miR-181a group were significantly higher than those of miR-NC group (all P<0.05). Conclusions:MiR-181a promotes the growth of chondrosarcoma cells through PTEN-mediated glycolysis.

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