1.Mechanism of Xiezhuo Jiedu Recipe in Preventing Colorectal Adenoma in Mice Through miRNA-34a-5p/PI3K/Akt Signalling Pathway
Sujie JIA ; Chaodi SUN ; Yifan ZHANG ; Xiaomeng LANG ; Jianping LIU ; Xin KANG ; Shijie REN ; Jingyuan LIU
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(11):156-165
ObjectiveKey microRNAs (miRNAs) of colorectal adenoma (CRA) were identified and analyzed by bioinformatics methods, and differentially expressed genes (DEGs) were screened to construct regulatory relationships. The mechanism of Xiezhuo Jiedu recipe in preventing CRA was speculated and verified by animal experiments. MethodThe miRNAs dataset GSE50194 was obtained from the Gene Expression Omnibus (GEO) database of intestinal mucosal tissue of CRA patients, and the differentially expressed miRNAs were screened by GEO2R and Excel. TargetScan, miRTarbase, and miRDB databases were used to predict the target genes of the differentially expressed miRNAs, and an intersection was obtained. Key DEGs were screened through the STRING database and Cytoscape software, and the TRRUST database was used to predict downstream binding transcription factors (TFs). The mRNA intersection was enriched by gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) in the Metascape database. DIANA TOOLS were applied to perform KEGG enrichment analysis of key miRNAs, and the key signaling pathways were selected for animal experiments. In animal experiments, the CRA mice model was established by using sodium glycan sulfate (DSS) drinking combined with intraperitoneal injection of azomethane oxide (AOM), and Xiezhuo Jiedu recipe and aspirin were given by intragastric administration at the same time. The experiment lasted for nine weeks. The pathological changes in intestinal tissue were observed by hematoxylin-eosin (HE) staining. Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR) was used to detect the mRNA expression of miR-34a-5p in adenoma tissue. Protein expression levels of phosphatidylinositol 3-kinase (PI3K), protein kinase B (Akt), phosphoryl-PI3K (p-PI3K), phosphoryl-Akt (p-Akt), and B cell lymphoma (Bcl)-2 were detected by Western blot. The expression of Cyclin D1 (CCND1) was detected by immunohistochemistry (IHC). In situ terminal transferase labeling (TUNEL) was used to detect apoptosis of adenoma tissue cells. ResultThe GEO database screened the GSE50194 dataset, and miR-34a-5p was selected as the research object from CRA and normal tissue. A total of 93 DEGs were selected. Among them, GO and KEGG enrichment analyses were closely related to biological processes such as transcriptional regulatory complex, RNA polymerase Ⅱ transcriptional regulatory complex, enzyme-linked receptor protein signaling pathway, and DNA-binding transcriptional activator activity, cancer pathway, PI3K/Akt pathway, etc. miR-34a-5p is mainly enriched in PI3K/Akt, cell cycle, and colorectal cancer pathways. Five key DEGs were screened out through the Matescape database, among which Bcl-2 and CCND1 were the key DEGs of miR-34a-5p. Further screening of the TFs of key DEGs revealed that E2F transcription factor 1 (E2F1) and tumor protein P53 (TP53) were the main TFs of Bcl-2 and CCND1. Animal experiments showed that Xiezhuo Jiedu recipe could effectively up-regulate mRNA level of miR-34a-5p, down-regulate the expression of PI3K, Akt, Bcl-2, p-PI3K, and p-Akt proteins in the intestinal tissue of CRA mice, down-regulate the positive expression rate of CCND1, and increase the apoptosis rate of intestinal epithelial cells. ConclusionIt is speculated that Xiezhuo Jiedu recipe may inhibit the abnormal proliferation and promote the apoptosis of intestinal epithelial cells in CRA mice by regulating the miR-34a-5p/PI3K/Akt signaling pathway, thus playing a role in the prevention of CRA.
2.Mechanism of Modified Guizhi Fulingwan in Regulating Mitochondrial Apoptosis Pathway Through PTEN/PI3K/Akt Pathway to Prevent Colorectal Adenoma in Mice
Sujie JIA ; Longhui LIU ; Yifan ZHANG ; Xiaomeng LANG ; Jianping LIU ; Xin KANG ; Chaodi SUN ; Jingyuan LIU
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(19):10-20
ObjectiveTo investigate the effect and mechanism of modified Guizhi Fulingwan in preventing colorectal adenoma (CRA) in mice by regulating mitochondrial apoptosis pathway through the regulation of the phosphatase and tensin homolog (PTEN)/phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) pathway. MethodSixty SPF-grade male C57BL/6 mice were randomly divided into six groups: Normal group, model group, low, medium, and high dose groups of modified Guizhi Fulingwan (13, 26, 52 g·kg-1·d-1), and positive control aspirin group (0.015 g·kg-1·d-1). A mouse model of CRA was chemically induced using azoxymethane (AOM) and dextran sulfate sodium (DSS). During the modeling process, mice received modified Guizhi Fulingwan or aspirin. Body weight of mice was measured weekly during the treatment. After 9 weeks, the number of adenomas formed was observed. Serum levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-1β (IL-1β) were determined by enzyme-linked immunosorbent assay (ELISA). Hematoxylin-eosin (HE) staining was used to observe the histopathologic changes in adenoma tissues. The expression of Cyclin D1 and proliferative nuclear antigen (Ki67) was detected by immunohistochemistry (IHC). Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) was used to assess the apoptosis in adenoma tissues. Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR) and Western blot were used to observe the mRNA and protein expression levels of PTEN, PI3K, Akt, phosphorylated PI3K (p-PI3K), phosphorylated Akt (p-Akt), B-cell lymphoma-2 (Bcl-2), Bcl-2 associated X protein (Bax), cytochrome C (Cyt C), Caspase-9, and caspase-3. ResultCompared with the normal group, the model group showed no significant change in body weight from week 1 to week 2, but a significant decrease from week 3 to week 9 (P<0.05,P<0.01). The colorectal length was significantly shortened, and the colorectal weight increased with visible varying sized tumor-like protrusions on the mucosal surface (P<0.01). Serum levels of TNF-α, IL-6, and IL-1β were elevated (P<0.01). Histopathology showed disordered epithelial gland structure, elongated nuclei with pathological mitosis, and numerous lymphocytic infiltrations in the lamina propria. The positive expression rates of Cyclin D1 and Ki67 were significantly increased (P<0.01), while the apoptosis rate of adenoma cells was significantly decreased (P<0.01). Expression levels of PI3K, Akt, Bcl-2 mRNA and proteins, as well as p-PI3K and p-Akt proteins, were significantly increased (P<0.01), whereas PTEN, Bax, Cyt C, Caspase-9, and Caspase-3 mRNA and protein levels were significantly decreased (P<0.05, P<0.01). Compared with the model group, all drug treatment groups showed an increase in body weight (P<0.01), decreased intestinal weight, increased colorectal length, reduced number of adenomas significantly (P<0.05, P<0.01), and significantly lowered serum levels of TNF-α, IL-6, and IL-1β (P<0.01). Histopathology indicated improved glandular structure and reduced neutrophil infiltration in the mucosal lamina propria. The positive expression rates of Cyclin D1 and Ki67 significantly decreased (P<0.01), while the apoptosis rate of adenoma cells significantly increased (P<0.05, P<0.01). Expression levels of PI3K, Akt, Bcl-2 mRNA and proteins, and p-PI3K and p-Akt proteins were significantly reduced (P<0.05, P<0.01), while PTEN, Bax, Cyt C, Caspase-9, and Caspase-3 mRNA and protein levels significantly increased (P<0.05, P<0.01). The high-dose modified Guizhi Fulingwan group exhibited the most significant intervention effects. ConclusionModified Guizhi Fulingwan may prevent CRA in mice by regulating the PTEN/PI3K/Akt signaling pathway and inducing the mitochondrial apoptosis pathway.
3.Expert recommendation on the management of perioperative hyphema and intraocular pressure spike following goniotomy
Xiulan ZHANG ; Xiaojing PAN ; Min KE ; Li TANG ; Lin XIE ; Liming TAO ; Sujie FAN ; Guangxian TANG ; Xuanchu DUAN ; Huiping YUAN
Chinese Journal of Experimental Ophthalmology 2024;42(10):881-886
Goniotomy (GT) is a safe and effective type of minimally invasive glaucoma surgery (MIGS) extensively utilized in China.It is particularly suited for treating primary open-angle glaucoma and advanced primary angle-closure glaucoma.Although GT is generally safe, hyphema and postoperative intraocular pressure (IOP) spikes remain common complications after GT.Currently, there is no standardized protocol for managing these issues, which can impact clinicians' assessment of surgical outcomes and potentially affect the prognosis.Therefore, it is crucial to establish comprehensive and detailed management protocols for perioperative hyphema and IOP spike following GT.This will guide clinical practitioners in managing complications appropriately and systematically, thereby promoting the further development and refinement of MIGS.To address these concerns, several domestic glaucoma treatment experts along with members of the Glaucoma Society of Ophthalmology, Guangdong Medical Association reviewed existing literature and held recommendation meetings to develop a guideline for managing perioperative hyphema and IOP spikes following GT.It includes defining perioperative hyphema in GT, discussing its high-risk factors and outcomes, exploring methods for prevention prior to surgery and techniques to reduce bleeding during the procedure, and managing postoperative hemorrhage.Additionally, it covers defining IOP spikes after GT, investigates their causes and contributing factors, and outlines management strategies and anticipated outcomes to provide a valuable resource for clinicians.
4.Expert recommendations of phacoemulsification cataract extraction and intraocular lens implantation combined with goniosynechialysis and goniotomy for advanced PACG with cataract
Xiulan ZHANG ; Yunhe SONG ; Sujie FAN ; Li TANG ; Lan LU ; Lin XIE ; Guangxian TANG ; Huiping YUAN ; Minwen ZHOU
Chinese Journal of Experimental Ophthalmology 2023;41(2):97-100
With high incidence, high disability rate and serious impact on patients' quality of life, advanced primary angle-closure glaucoma (PACG) with cataract is a severe eye disease in China and its main treatment method is surgery.Phacoemulsification cataract extraction and intraocular lens implantation (PEI) combined with trabeculectomy has been used to treat advanced PACG with cataract, but there are many postoperative complications.Recently, combined PEI, goniosynechialysis (GSL) and goniotomy (GT) has been proven to be a safe and effective surgical treatment for advanced PACG with cataract.At present, the combined PEI+ GSL+ GT surgery has been widely applied, but there is still a lack of uniform standards for its clinical application.Therefore, it is necessary to formulate a detailed and complete recommendation of the surgical procedures for PEI+ GSL+ GT, to standardize its application in clinical practice.Based on the analysis of the existing problems, some glaucoma experts in China have formulated detailed and complete operation norms, as well as expert recommendations on surgical indications and contraindications, anesthetic methods, surgical techniques and perioperative medication to standardize the application process of PEI+ GSL+ GT in clinical practice.
5.Expert recommendations of surgical technique for peripheral iridectomy with goniosynechialysis and goniotomy
Xiulan ZHANG ; Fengbin LIN ; Sujie FAN ; Li TANG ; Guangxian TANG ; Lin XIE ; Lan LU ; Huiping YUAN ; Xin NIE
Chinese Journal of Experimental Ophthalmology 2023;41(2):101-103
Minimally invasive glaucoma surgery (MIGS) has been successfully incorporated in clinical practice in recent years.Increasing evidence shows that MIGS also plays an increasingly important role in the treatment of primary angle-closure glaucoma (PACG). Surgical peripheral iridectomy (SPI) plus goniosynechialysis (GSL) and goniotomy (GT), as a new procedure, has been proven to be safe and effective in the treatment of PACG with no or mild cataracts.However, there is still a lack of uniform standards for indications, surgical procedures, and perioperative medication.Therefore, it is necessary to formulate a detailed and complete expert recommendations on surgical procedures to standardize the application of combined SPI+ GSL+ GT in the treatment.Some experts in glaucoma treatment and management in China have discussed the current problems and developing trend in MIGS for PACG and put forward the expert recommendations of standard process, including indications, anaesthetic methods, surgical site, operating procedure and rational administration of drugs in perioperation, in order to standardize the medical process of clinicians using combined SPI+ GSL+ GT in PACG treatment and lay a foundation for better evaluation of the efficacy of MIGS.
6.Surgical outcome and safety of peripheral iridectomy plus goniosynechialysis and goniotomy in the treatment of advanced primary angle-closure glaucoma
Fengbin LIN ; Ping LU ; Yunhe SONG ; Xinbo GAO ; Yingzhe ZHANG ; Xin NIE ; Yuying PENG ; Xiaoyan LI ; Xiaomin ZHU ; Hengli ZHANG ; Yi ZHANG ; Lin XIE ; Guangxian TANG ; Li TANG ; Sujie FAN ; Xiulan ZHANG
Chinese Journal of Experimental Ophthalmology 2023;41(2):134-139
Objective:To evaluate the preliminary effectiveness and safety of surgical peripheral iridectomy (SPI) combined with goniosynechilysis (GSL) and goniotomy (GT) in the treatment of advanced primary angle-closure glaucoma (PACG).Methods:A multicenter observational case series study was performed.Thirty-five eyes of 27 patients with advanced PACG, who underwent SPI+ GSL+ GT with a follow-up of at least 6 months, were included from August 2021 to January 2022 at Zhongshan Ophthalmic Center, Handan City Eye Hospital, Shijiazhuang People's Hospital, West China Hospital of Sichuan University, and the Third Affiliated Hospital of Chongqing Medical University.The mean follow-up time was 9(7, 10) months.Pre- and post-operative best corrected visual acuity (BCVA) and intraocular pressure (IOP) were measured with an ETDRS chart and a Goldmann applanation tonometer, respectively.The number of anti-glaucoma medications applied before and after surgery was recorded, and the complications after surgery were analyzed.Success rate of surgery was calculated.Complete surgical success was defined as an IOP of 5-18 mmHg (1 mmHg=0.133 kPa) and 20% reduction from baseline without anti-glaucoma medication or reoperation.Qualified success was defined as achieving criterion of complete success under anti-glaucoma medications.This study adhered to the Declaration of Helsinki.The study protocol was approved by the Ethics Committee of Zhongshan Ophthalmic Center, Sun Yat-sen University (No.2021KYPJ177). Written informed consent was obtained from each subject.Results:The mean preoperative IOP was (30.83±8.87)mmHg, which was significantly decreased to (15.69±3.70)mmHg at 6 months after the surgery ( t=8.588, P<0.001), with a 44.00% (34.78%, 60.00%) decline of 13.00(8.00, 21.00)mmHg.The median number of anti-glaucoma medications was significantly reduced from 2(0, 3) preoperatively to 0 (0, 1) postoperatively ( Z=-3.659, P<0.001). The mean preoperative and postoperative 6-month BCVA were 0.80(0.63, 1.00) and 0.80(0.60, 1.00), respectively, showing no significant difference ( Z=-0.283, P=0.777). Complete surgical success rate was 62.86%(22/35), and the qualified success rate was 91.43%(32/35). Surgical complications mainly included hyphema (6/35), IOP spike (3/35), and shallow anterior chamber (4/35). There was no vision-threatening complication. Conclusions:SPI+ GSL+ GT is preliminarily effective and safe in the treatment of advanced PACG, which provides a new option for PACG.
7.Expert consensus recommendations of surgical technique for goniosynechialysis
Xiulan ZHANG ; Fengbin LIN ; Guangxian TANG ; Huiping YUAN ; Lin XIE ; Lan LU ; Sujie FAN ; Li TANG ; Xin NIE ; Minwen ZHOU
Chinese Journal of Experimental Ophthalmology 2023;41(9):843-845
Minimally invasive glaucoma surgery (MIGS) has been successfully incorporated in clinical practice in recent years.Increasing evidence shows that it also plays an important role in the treatment of primary angle-closure glaucoma (PACG). Goniosynechialysis (GSL) is a key surgical procedure used by MIGS for PACG, which involves separating the peripheral anterior synechia and reopening the angle.However, there is still a lack of uniform standards for indications and surgical procedures.Therefore, it is necessary to formulate a detailed and complete expert consensus on surgical procedures to standardize the application of clinicians in the treatment.
8.Evaluation of Clinical Efficacy of Shengmaisan Granules in Inhibiting Myocardial Fibrosis in Patients with Chronic Heart Failure with Qi-Yin Deficiency Syndrome Based on CMR
Yuedong YANG ; Maolin WANG ; Juan ZHAO ; Mingyu SHI ; Chenhan MAO ; Sujie ZHANG ; Hao ZHI ; Jianping SHEN
Chinese Journal of Experimental Traditional Medical Formulae 2023;29(23):89-97
ObjectiveTo evaluate the effect of Shengmaisan granules on myocardial fibrosis in chronic heart failure patients with Qi-Yin deficiency syndrome by cardiac magnetic resonance (CMR) imaging and serological indicators. MethodSixty-six chronic heart failure patients with Qi-Yin deficiency syndrome who visited the Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine from October 2021 to January 2023 were selected. The patients were assigned into a control group (33 cases) and an observation group (33 cases) by the minimization random method. Both groups received standardized Western medicine treatment for heart failure. In addition, the control group was treated with placebo granules, and the observation group with Shengmaisan granules for a course of 6 months. The baseline data, clinical efficacy, TCM symptom scores, serological indicators [high-sensitivity C-reactive protein (hs-CRP), soluble growth stimulation expressed gene 2 protein (sST2), pro-collagen Ⅲ N-terminal peptide (PⅢNP), interleukin (IL)-6, IL-11, transforming growth factor-β1 (TGF-β1)], echocardiography [Left atrial diameter (LAD), left ventricular end systolic diameter (LVEDs), left ventricular end diastolic diameter (LVEDd)] and CMR indicators [left ventricular ejection fraction (LVEF), myocardial extracellular volume fraction (ECV), and longitudinal relaxation time (T1)] were compared between the two groups. ResultFinally, 31 patients in the control group and 30 patients in the observation group were included. There was no significant difference in baseline data or indicators between the two groups before treatment. Compared with those before treatment, the scores of TCM symptoms (shortness of breath, fatigue, palpitations, spontaneous or night sweats, thirst/dry throat, feverish feeling in palms and soles, and edema in lower limbs), total score of TCM symptoms, ECV, T1, inflammation/fibrosis indicators (hs-CRP, sST2, PⅢNP, IL-6, IL-11, and TGF-β1) in observation group decreased (P<0.05, P<0.01), and the scores of TCM symptoms (except feverish feeling in palms and soles), T1, and inflammation/fibrosis indicators in the control group decreased (P<0.05, P<0.01). After treatment, the observation group had lower scores of TCM symptoms (except feverish feeling in palms and soles and edema in lower limbs), ECV, T1, and inflammation/fibrosis indicators than the control group (P<0.05, P<0.01). After treatment, the total response rate in the observation group was 93.33% (28/30), which was higher than that (80.65%, 25/31) in the control group (Z=2.976, P<0.01). There was no significant difference in adverse reactions between the two groups during treatment. ConclusionFor patients with chronic heart failure with Qi-Yin deficiency syndrome, Shengmaisan Granules can alleviate the TCM symptoms, reduce inflammation, and inhibit myocardial fibrosis by regulating the TGF-β1/IL-11 signaling axis.
9.Apolipoprotein B and ischemic stroke
Xuejing YIN ; Zhichao FENG ; Sujie ZHU ; Caixia YIN ; Lifang ZHANG ; Lihua BAO ; Jinhua CHEN
International Journal of Cerebrovascular Diseases 2022;30(9):700-705
Studies have shown that plasma apolipoprotein B (ApoB) has a good predictive value for ischemic stroke and plays an important role in the prevention and treatment of ischemic stroke. More and more guidelines and consensus opinions began to recommend ApoB as a routine intervention target. This article reviews the biological characteristics, clinical detection advantages, and role and treatment prospect of ApoB in the prevention and treatment of ischemic stroke.
10.Is Schlemm canal surgery suitable for primary angle-closure glaucoma?
Li TANG ; Huiping YUAN ; Guangxian TANG ; Sujie FAN ; Lan LU ; Minwen ZHOU ; Lin XIE ; Xin NIE ; Xiulan ZHANG
Chinese Journal of Experimental Ophthalmology 2022;40(4):340-344
Primary angle-closure glaucoma (PACG) is a common subtype of glaucoma and one of the leading causes of blindness in Asia.Trabeculectomy has been recognized as an effective filtering surgery for PACG and is widely used in clinical practice, but its high risk of postoperative complications, especially bleb scarring over time can not be ignored.Nowadays, non-bleb-based minimally invasive glaucoma surgeries (MIGS) have attracted much attention.Surgeries opening, restoring, or expanding Schlemm canal to reconstruct aqueous humor outflow pathway is one of the MIGS and able to achieve moderate intraocular pressure (IOP) reduction, which has been widely used in the treatment of primary open-angle glaucoma (POAG) for a long time.However, based on the pathogenesis of PACG and its similar pathological changes in Schlemm canal to POAG, some retrospective studies and prospective single-arm studies discovered that Schlemm canal surgery combined with phacoemulsification and/or goniosynechialysis appears to lower IOP well and safe in PACG eyes in recent years.Whether Schlemm canal surgery is also suitable or effective for PACG is getting some attention and is still controversial up to now, mostly due to some differences in pathogenesis between PACG and POAG, it is necessary to perform randomized controlled trials to confirm the efficacy of Schlemm canal surgery for PACG and upgrade the therapeutic strategy of PACG.

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