Discovery of small molecule degraders for modulating cell cycle / 医学前沿

The cell cycle is a complex process that involves DNA replication, protein expression, and cell division. Dysregulation of the cell cycle is associated with various diseases. Cyclin-dependent kinases (CDKs) and their corresponding cyclins are major proteins that regulate the cell cycle. In contrast to inhibition, a new approach called proteolysis-targeting chimeras (PROTACs) and molecular glues can eliminate both enzymatic and scaffold functions of CDKs and cyclins, achieving targeted degradation. The field of PROTACs and molecular glues has developed rapidly in recent years. In this article, we aim to summarize the latest developments of CDKs and cyclin protein degraders. The selectivity, application, validation and the current state of each CDK degrader will be overviewed. Additionally, possible methods are discussed for the development of degraders for CDK members that still lack them. Overall, this article provides a comprehensive summary of the latest advancements in CDK and cyclin protein degraders, which will be helpful for researchers working on this topic.

Early efficacy of rotational femoral neck osteotomy with preservation of the round ligament in treating subchondral insufficiency fracture of the femoral head in young and middle-aged population / 中华创伤杂志

Objective:To investigate the short-term efficacy of rotational femoral neck osteotomy with preservation of the round ligament in the treatment of subchondral insufficiency fracture of the femoral head (SIFFH) in young and middle-aged people.Methods:A retrospective case series study was used to analyze the clinical data of 13 patients with SIFFH, who were admitted to 920th Hospital of Joint Logistics Support Force from January 2017 to January 2022. The patients included 10 males and 3 females, aged 22-49 years [(33.5±8.3)years]. There were 6 patients with fracture on the left hip and 7 on the right hip. All the patients were treated by rotational femoral neck osteotomy with preservation of the round ligament. Postoperatively, standardized joint functional training was given. The operative time and intraoperative bleeding were recorded. The modified Harris hip score and visual analogue score (VAS) were compared preoperatively, at 3, 6 months postoperatively and at the final follow-up. Radiological examinations were used to observe the occurrence of any collapse of the femoral head, non-union at osteotomy site or other complications.Results:The patients were followed up for 13-24 months [(17.9±3.1)months]. The operative time was (127.3±9.8)minutes, with the intraoperative bleeding of (393.9±21.9)ml. The values of modified Harris hip score were (61.6±3.3)points, (80.2±4.4)points, and (91.9±4.1)points at 3, 6 months postoperatively and at the final follow-up, respectively, being significantly higher than the preoperative (51.4±3.5)points (all P<0.05), and there were significant differences between different postoperative timepoints (all P<0.05). The values of VAS were (4.9±1.1)points, (3.0±0.9)points, and (1.4±0.5)points at 3, 6 months postoperatively and at the final follow-up, respectively, being significantly lower than preoperative (6.7±0.9)points (all P<0.05), and there were significant differences between different postoperative timepoints (all P<0.05). Imaging examination showed no femoral head collapse, with all the bones healed at the osteotomy site. There were no serious complications such as bone non-union, incision infection or peripheral nerve injury. Conclusion:Rotational femoral neck osteotomy with preservation of the round ligament in treating SIFFH in the young and middle-aged population has the advantages of shortened operative time, less intraoperative bleeding, promoted hip function recovery, attenuated pain and decreased complications, showing a satisfactory early effect.

Low expression of MYCN promotes cisplatin resistance by suppressing cisplatin-induced apoptosis in epithelial ovarian cancer.

Epithelial ovarian cancer (EOC) is the most common cause of gynecological cancer-associated mortality. Cisplatin is one of the most effective chemotherapeutic drugs used in EOC; however, its use can lead to relapse due to cisplatin resistance. MYCN sensitizes neuroblastoma to undergo cisplatin-induced apoptosis. However, to the best of our knowledge, there have been no studies to date on the association between MYCN and cisplatin resistance in EOC. Therefore, the present study assessed this association. Datasets from The Cancer Genome Atlas database were used. The overall survival (OS) of patients receiving platin-based therapy was analyzed using Kaplan-Meier Plotter software. RNA sequencing data of 300 patients with EOC were downloaded from cBioportal. The co-expressed genes were subjected to 'Kyoto Encyclopedia of Genes and Genomes' analysis using DAVID software. For gene set enrichment analysis, the expression matrix was separated according to the median expression of MYCN, which was selected for hallmark gene set enrichment. Immunohistochemistry was used to assess MYCN expression in EOC tissue. Western blotting was used to evaluate MYCN, p53, Bax and Bcl-2 protein expression levels in EOC cells. Cell viability and apoptosis were assessed using Cell Counting Kit-8 and flow cytometry, respectively. The results demonstrated that MYCN upregulation was associated with increased cisplatin sensitivity and prolonged OS of patients with EOC and patients receiving platin-based therapy. Cisplatin downregulated MYCN expression in cisplatin-sensitive, but not resistant, EOC cells. The genes co-expressed with MYCN were primarily involved in pathways involved in 'chemotherapeutic resistance' and 'apoptosis'. MYCN enriched the apoptosis and p53 signaling pathways in hallmark gene sets. Cells in which MYCN was knocked down demonstrated significantly increased cisplatin resistance; however, MYCN overexpression in cisplatin-resistant cells restored cisplatin sensitivity. Collectively, the present study demonstrated that MYCN downregulation promoted cisplatin resistance by suppressing cisplatin-induced apoptosis in EOC.

Correction of coupling error in contact-type ultrasonic evaluation of bolt axial stress.

The stress monitoring of bolted connections is crucial in the evaluation of mechanical systems' structural health, and the ultrasonic method using TOF (Time of Flight) is considered promising in this application. However, the discrete nature of couplant layer characteristics can deteriorate the robustness of the ultrasonic method significantly. Here, for the purpose of deducting the coupling error, a compensating method of TOF is proposed. In this method, the components of the waves backscattering from bolt bearing surface within the temporal signal are filtered and utilized. The analytical coupling error correction model is established and the influences of the installation eccentricity upon the model are analyzed. Meanwhile, the proposed method is further verified by a finite element simulation and the results are consistent with the analytical derivations. Ultimately, the proposed method is experimentally validated and the scattering components are extracted from the pulse echo signal by using the synchrosqueezed wavelet transform. The results imply that, after being compensated by the proposed method, the stress measurement error decreased from 5% to 1%. This research provides a novel perspective in reducing the coupling error in a concise manner and is potential in improving the practicality of the ultrasonic bolt axial stress measurement methods.

Chemotherapy versus chemoradiotherapy for FIGO stages IB1 and IIA1 cervical squamous cancer patients with lymphovascular space invasion: a retrospective study.

PURPOSE: To evaluate the impact of different adjuvant therapy on IB1 and IIA1 stage cervical squamous cell cancer patients with lymphovascular space invasion. It also aimed to analyze the relationship between lymphovascular space invasion and other clinical pathological characteristics on IB1 and IIA1 stage cervical squamous cell cancer patients. METHODS: This retrospective observational study collected data of FIGO stages IB1 and IIA1 squamous cervical cancer patients at the First Affiliated Hospital of Chongqing Medical University between 2014 and 2018. A correlation analysis between lymphovascular space invasion and other clinical or pathological factors was conducted. Prognosis analysis of patients with lymphovascular space invasion were performed to assess associations between clinical-pathological characteristics and survival. RESULTS: A total of 357 women were identified including 110 (30.8%) with lymphovascular space invasion, 247 (69.2%) without lymphovascular space invasion. Both middle 1/3 cervical stromal invasion (p = 0.000) and deep 1/3 cervical stromal invasion (p = 0.000) were independently associated with lymphovascular space invasion. Among lymphovascular space involved women, tumor differentiation (P = 0.001) and postoperative therapy (P = 0.036) had a significant influence on disease recurrence. Multivariate analysis showed that lymph node metastasis (P = 0.017), poorer tumor differentiation (P = 0.036) and postoperative chemotherapy alone (P = 0.021) can increase the risk of tumor relapse. CONCLUSION: Our study suggested that the presence of deep stromal invasion independently increases the risk of lymphovascular space invasion. Compared with chemotherapy, chemoradiotherapy seems to improve progression-free survival in squamous cervical cancer patients with lymphovascular space invasion.

Synthesis of selective PAK4 inhibitors for lung metastasis of lung cancer and melanoma cells

The p21 activated kinase 4 (PAK4) is serine/threonine protein kinase that is critical for cancer progression. Guided by X-ray crystallography and structure-based optimization, we report a novel subseries of C-3-substituted 6-ethynyl-1H-indole derivatives that display high potential and specificity towards group II PAKs. Among these inhibitors, compound 55 exhibited excellent inhibitory activity and kinase selectivity, displayed superior anti-migratory and anti-invasive properties against the lung cancer cell line A549 and the melanoma cell line B16. Compound 55 exhibited potent in vivo antitumor metastatic efficacy, with over 80% and 90% inhibition of lung metastasis in A549 or B16-BL6 lung metastasis models, respectively. Further mechanistic studies demonstrated that compound 55 mitigated TGF-β1-induced epithelial-mesenchymal transition (EMT).

Exposure to N-monoacetyl-p-phenylenediamine impaired ovarian function in mice.

p-Phenylenediamine (PPD) is the main constituent of permanent hair dye and is also widely used in the photographic and rubber industries. PPD and its metabolites have been shown to increase the risk of cancer (especially ovarian cancer); however, their effect on female reproduction is unclear. We investigated the effects of the PPD metabolite N-monoacetyl-PPD (MAPPD) on mouse blastocyst development and ovarian function. Sixty 8-week-old female Kunming mice were administered at 0-, 100-, and 300-mg/kg/day MPPD by gavage for 28 days. KGN (human ovarian granulosa cells) were treated with MAPPD at concentrations of 0, 50, 100, and 300 µg/ml for 48 h. The number of abnormal blastocysts increased on gestation day 3.5 in all treatment groups. Compared with the control group, in MAPPD exposed group, the number of antral follicles decreased, the levels of E2 and P4 decreased in ovarian tissue, the serum levels of E2 , P4 , luteinizing hormone (LH), and T decreased, and follicle-stimulating hormone (FSH) increased. The expression of FSH receptor (FSHR) and LH receptor (LHR) was significantly downregulated, and the level of oxidative stress was significantly increased. In KGN cells, the level of reactive oxygen species increased in a dose-dependent manner, and the mRNA levels of FSHR, LHR, and aromatase increased. These results suggest that MAPPD inhibits FSH- and LH-induced aromatase activity by causing oxidative stress, which decrease hormone levels, leading to abnormal follicle development. Meanwhile, MAPPD exposure could affect early embryonic development abnormalities by affecting the quality of ovum.

Design, synthesis, and biological evaluation of multiple targeting antimalarials

Malaria still threatens global health seriously today. While the current discoveries of antimalarials are almost totally focused on single mode-of-action inhibitors, multi-targeting inhibitors are highly desired to overcome the increasingly serious drug resistance. Here, we performed a structure-based drug design on mitochondrial respiratory chain of

Beneficial effects of Coicis Semen formula on high-fat diet-induced obesity in mice / 中草药

Objective: To study the effects and mechanism of Coicis Semen formula on high-fat diet-induced obesity in mice. Methods: C57BL/6J male mice were fed on chow or high-fat diet. After three months, except for control group, the obese mice (body weight more than 20% of the control mice) were randomly divided into model group (model), Coicis Semen formula low-dose group (0.59 g/kg, F-low), Coicis Semen formula high-dose group (1.17 g/kg, F-high) and positive control group (orlistat, 15.6 mg/kg, positive control). F-low, F-high and positive control groups were treated orally for two months, and the control group and the model group were given an equal volume of saline. The fat content of mice was quantified by computed tomography (CT) and magnetic resonance imaging (MRI), the size of adipocytes was observed by tissue staining and the level of inflammatory cytokines was detected by qRT-PCR. Results: The results showed that after treatment with Coicis Semen formula, the relative body weight, food utilization ratio and waist circumference were significantly reduced (P < 0.05). An oral glucose tolerance test elucidated that Coicis Semen formula could improve glucose tolerance (P < 0.05). CT and MRI results indicated that the abdominal fat thickness and whole-body fat content of Coicis Semen formula groups were decreased (P < 0.05), which were also confirmed by the adipose tissue weight and HE staining results. Meanwhile, after administration of Coicis Semen formula, the liver weight decreased, less lipid droplets accumulated, and serum triglyceride (TG) and total cholesterol (TC) levels were also significantly lowered (P < 0.05). Coicis Semen formula also significantly down-regulated serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) levels and inflammatory factors tumor necrosis factor (TNF-α) and interleukin-6 (IL-6) in liver (P < 0.05). Conclusion: Coicis Semen formula prevented high-fat diet-induced obesity by reducing lipid aggregation and inflammatory factor expression.

Discovery of Novel Neuraminidase Inhibitors by Structure-Based Virtual Screening, Structural Optimization, and Bioassay.

Neuraminidase (NA) is a significant therapeutic target for treating influenza. In this study, a new lead NA inhibitor AN-329/10738021 was discovered by structure-based virtual screening, molecular dynamics simulations, and bioassay validation. Optimization of lead AN-329/10738021, which holds a novel scaffold of N'-benzylidene benzohydrazone, leads to discovery of some novel NA inhibitors Y-1-Y-11. Compound Y-1 exerts the best inhibition activity (IC50 = 0.21 µM) against NA, which is better than oseltamivir carboxylate (OSC) (IC50 = 3.04 µM) and lead AN-329/10738021 (IC50 = 1.92 µM). Molecular docking analysis indicates that the good potency of Y-1 may be ascribed to the elongation of the benzylidene moiety of the molecule to the 430-cavity. The results of this study may offer useful reference for development of novel NA inhibitors.

Correction to: Developing potent PROTACs tools for selective degradation of HDAC6 protein

In the original publication the title of X axis in figure 1G is incorrectly published as "Compound (µmol/L)". The correct title of X axis in figure 1G should be read as "Compound (nmol/L)".

Design, synthesis and biological evaluation of novel zanamivir derivatives as potent neuraminidase inhibitors.

Neuraminidase (NA) is an important antiviral drug target. Zanamivir is one of the most potent NA inhibitors. In this paper, a series of zanamivir derivatives as potential NA inhibitors were studied by combination of molecular modeling techniques including 3D-QSAR, molecular docking, and molecular dynamics (MD) simulation. The results show that the best CoMFA (comparative molecular field analysis) model has q2 = 0.728 and r2 = 0.988, and the best CoMSIA (comparative molecular similarity indices analysis) model has q2 = 0.750 and r2 = 0.981, respectively. The built 3D-QSAR models show significant statistical quality and excellent predictive ability. Seven new NA inhibitors were designed and predicted. 20 ns of MD simulations were carried out and their binding free energies were calculated. Two designed compounds were selected to be synthesized and biologically evaluated by NA inhibition and virus inhibition assays. One compound (IC50 = 0.670 µM, SI > 149) exhibits excellent antiviral activity against A/WSN/33 H1N1, which is superior to the reference drug zanamivir (IC50 = 0.873 µM, SI > 115). The theoretical and experimental results may provide reference for development of new anti-influenza drugs.

Expression of IL-17 in Patients with Both PE and OSAHS and Its Clinical Significance / 昆明医科大学学报

Objective To observe the relationship of IL-17 and arterial blood gas, fibrin fragment D (D-D) in patients with both pulmonary embolism (PE) and obstructive sleep apnea-hypopnea syndrome (OSAHS). Methods We collected 20 patients with both PE and OSAHS and 43 patients with only PE who hospitalized in the first ward of pneumology department of the Second Affiliated Hospital of Kunming Medical University, then measured D-D, IL-17 in venous blood and arterial blood gas and recorded them to analysis.Re s ults PO2 in patients with both PE and OSAHS was significantly lower than that in patients with only PE, while D-D and IL-17 of the latter were markedly lesser than the former. Conclus ions The expression of IL-17 between the 2 groups of patients has statistically significant difference. What's more, the expression of IL-17 is positively associated with hypercoagulability and Body Mass Index (BMI), and the result shows a negative relation between arterial blood oxygen partial pressure and IL-17, suggesting that IL-17 may be relate to the common progress of PE and OSASH. Thus, IL-17 can be used in the detection of patients with both PE and OSASH

Viral metagenomics analysis of poultry faeces in live poultry market, Haikou, China

Objective:To conduct in-depth study of the distribution and diversity of viruses in poultry is of great importance in monitoring the emergence of interspecies transmission of novel viruses that may cause epidemics with public health significance. Poultry is an economically important source of meat, eggs and feathers which plays an important role as natural reservoirs of many pathogenic viruses. Compared with wild animals, poultry have more frequent interactions and therefore opportunities to transmit their viruses to human.Methods:To study the viromes of different types of poultry in Hainan, China, we used metagenomics for deep viral nucleic acid sequencing of the faecal samples collected from chickens, ducks and pigeons from a live poultry market in Haikou.Result:The poultry viromes were identified by sequence similarity comparisons of viral reads (BLASTxE score, <5) against viral reference database. A total of 15 309 viral reads were obtained, approximately 13 063, 1 370 and 876 viral reads were generated from the chicken, duck, pigeon faecal samples, respectively. The majority of the sequences were homologous to the animal virus of Adenoviridae, Herpeaviridae, Picobirnaviridae, Reoviridae, Retroviridae, Circoviridae, Paramyxoviridae, Astroviridae, Caliciviridae, Coronaviridae, Picornaviridae, and Orthomyxoviridae. The VP4 and VP7 segments of a pigeon rotavirus, similar to fox rotavirus in group A, were sequenced and phylogenetically analyzed. The near full genome of a pigeon circovirus was also analyzed.Conclusion:The major types of poultry in a Haikou harbor many different families of viruses in their feces which may have the potential for interspecies transmissions. Further studies should be conducted to identify the most prevalent and important viruses among a larger number of poultry in Haikou and other areas in Hainan.

The positive role of tutorial system on the development of medical students / 中华医学教育探索杂志

The development of the healthcare industry puts forward higher and higher standards on the medical education, so an effective education management mode is needed urgently for medical schools to promote the cultivation of undergraduate medical students. Tutorial system has a positive effect in building the innovative thinking, critical thinking and clinical thinking of medical students. It also helps students' innovation ability training. This paper first introduces the overview of the implementation of tutorial system in medical colleges, and then expounds the specific implementation measures of the undergraduate tutorial system in the Third Military Medical University. Investigation data shows that, accompanied with these mea-sures, the numbers of article publishes and the achievements in various competitions have been raised whereas the psychological counseling needs decreased, indicating that the tutorial system has a strong posi-tive influence on the development of medical students.

miR-638 is a new biomarker for outcome prediction of non-small cell lung cancer patients receiving chemotherapy

MicroRNAs (miRNAs), a class of small non-coding RNAs, mediate gene expression by either cleaving target mRNAs or inhibiting their translation. They have key roles in the tumorigenesis of several cancers, including non-small cell lung cancer (NSCLC). The aim of this study was to investigate the clinical significance of miR-638 in the evaluation of NSCLC patient prognosis in response to chemotherapy. First, we detected miR-638 expression levels in vitro in the culture supernatants of the NSCLC cell line SPC-A1 treated with cisplatin, as well as the apoptosis rates of SPC-A1. Second, serum miR-638 expression levels were detected in vivo by using nude mice xenograft models bearing SPC-A1 with and without cisplatin treatment. In the clinic, the serum miR-638 levels of 200 cases of NSCLC patients before and after chemotherapy were determined by quantitative real-time PCR, and the associations of clinicopathological features with miR-638 expression patterns after chemotherapy were analyzed. Our data helped in demonstrating that cisplatin induced apoptosis of the SPC-A1 cells in a dose- and time-dependent manner accompanied by increased miR-638 expression levels in the culture supernatants. In vivo data further revealed that cisplatin induced miR-638 upregulation in the serum derived from mice xenograft models, and in NSCLC patient sera, miR-638 expression patterns after chemotherapy significantly correlated with lymph node metastasis. Moreover, survival analyses revealed that patients who had increased miR-638 levels after chemotherapy showed significantly longer survival time than those who had decreased miR-638 levels. Our findings suggest that serum miR-638 levels are associated with the survival of NSCLC patients and may be considered a potential independent predictor for NSCLC prognosis.

miR-638 is a new biomarker for outcome prediction of non-small cell lung cancer patients receiving chemotherapy

MicroRNAs (miRNAs), a class of small non-coding RNAs, mediate gene expression by either cleaving target mRNAs or inhibiting their translation. They have key roles in the tumorigenesis of several cancers, including non-small cell lung cancer (NSCLC). The aim of this study was to investigate the clinical significance of miR-638 in the evaluation of NSCLC patient prognosis in response to chemotherapy. First, we detected miR-638 expression levels in vitro in the culture supernatants of the NSCLC cell line SPC-A1 treated with cisplatin, as well as the apoptosis rates of SPC-A1. Second, serum miR-638 expression levels were detected in vivo by using nude mice xenograft models bearing SPC-A1 with and without cisplatin treatment. In the clinic, the serum miR-638 levels of 200 cases of NSCLC patients before and after chemotherapy were determined by quantitative real-time PCR, and the associations of clinicopathological features with miR-638 expression patterns after chemotherapy were analyzed. Our data helped in demonstrating that cisplatin induced apoptosis of the SPC-A1 cells in a dose- and time-dependent manner accompanied by increased miR-638 expression levels in the culture supernatants. In vivo data further revealed that cisplatin induced miR-638 upregulation in the serum derived from mice xenograft models, and in NSCLC patient sera, miR-638 expression patterns after chemotherapy significantly correlated with lymph node metastasis. Moreover, survival analyses revealed that patients who had increased miR-638 levels after chemotherapy showed significantly longer survival time than those who had decreased miR-638 levels. Our findings suggest that serum miR-638 levels are associated with the survival of NSCLC patients and may be considered a potential independent predictor for NSCLC prognosis.

Strategy for soluble expression of phage-displayed scFv antibody specific for zebrafish vitellogenin / 生物工程学报

We developed a new method for soluble expression of phage-displayed scFv antibody specific for zebrafish vitellogenin. The scFv antibody F5 could bind zebrafish vitellogenin specifically in phage-displayed form but not soluble form. The gene of scFv antibody F5 was cloned into vector pET 32a and transferred into Escherichia coli ori DE3. With inducible expression, soluble scFv antibody 32a-F5 was obtained successfully and could also specifically bind to zebrafish vitellogenin. The insoluble expression of phage-displayed scFv antibody was a common problem in the practical use of phage display. This study offered a feasible way to express soluble scFv antibodies with biological activity.

Smokers at higher risk for undetected antibody for oncogenic human papillomavirus type 16 infection.

OBJECTIVE: To determine the association between tobacco smoking and serologic evidence of human papillomavirus type 16 (HPV16)-specific antibodies among HPV16 DNA-positive women. DESIGN, SETTING, AND PARTICIPANTS: Baseline health history, physical examination, and laboratory data for 205 HPV16 DNA-positive women with no prior cytologic evidence of squamous intraepithelial lesions who were enrolled subsequently in a randomized clinical trial. MAIN OUTCOME MEASURE: HPV16-L1 antibody (anti-HPV16 antibody) detected from serum using RIA or ELISA. RESULTS: Eighty-seven percent (179 of 205) of women tested positive for HPV16 DNA using cervicovaginal swabs or lavage specimens, and 26 women showed similar results using swab specimens of external genitalia alone. HPV16-infected women who reported increasingly greater levels of daily cigarette smoking were less likely to test positive for anti-HPV16 antibodies than nonsmoking women (P = 0.02). Smokers were twice as likely as nonsmokers to test negative for anti-HPV16 antibodies, even after controlling for the effects of other covariates in the analyses (adjusted odds ratio, 0.5; 95% confidence limits, 0.2-0.9). Although Papanicolaou test findings and smoking characteristics were poorly correlated (r(2) = 0.01), women who showed atypical cells of unknown significance or squamous intraepithelial lesion were twice as likely to test anti-HPV16 antibody positive as women who showed normal Papanicolaou tests (adjusted odds ratio, 2.0; 95% confidence limits, 1.1-3.7). CONCLUSION: These data suggest that smoking may influence the long-term risk for cancer by perturbing early immune responses to the virus and may increase the likelihood of persistent infection. Patient education messages should alert women to this additional risk of smoking. A clinical trial of smoking cessation should be explored as a therapeutic intervention for primary HPV16 infection.

[Effects of different compositions of Gegenqinlian decoction on experimental shigellosis in rabbits].

OBJECTIVE: To investigate the relations between different compositions of Gegenqinlian decoction and their effects on experimental shigellosis in rabbits to explore the composition protocol of Gegenqinlian decoction. METHODS: Rabbit models of intestinal invasion induced by Shigella flexneri was established by directly inoculating the bacterium in the colon after cecum bypass operation. The effects of different compositions of Gegenqinlian decoction on the indexes of colitis and the bacterial count of Shigella in the colon content and colon tissue were investigated by orthogonal design. RESULTS: According to the bacterial count of Shigella in the colon, Coptis chinensis franch and Scutellaria baicalensis Georgi are the main effective drugs, but they antagonized each other, so that the best combination protocol was Coptis chinensis Franch only. CONCLUSION: Among the components of Gegenqinlian decoction, Coptis chinensis franch has the strongest pharmacological effect against bacteria and Glycyrrhina wralensis fisch is the most effective to ameliorate pathological lesions.