BACKGROUND:We have successfully established an animal model of small ear pig in southern Yunnan province with internal tension relieving technique combined with autologous Achilles tendon for anterior cruciate ligament reconstruction,and verified the stability and reliability of the model.However,whether internal tension relieving technique can promote the ligamentalization process of autologous Achilles tendon graft has not been studied. OBJECTIVE:To investigate the differences in the process of ligamentalization between conventional reconstruction and internal reduction reconstruction of the anterior cruciate ligament by gross view,histology and electron microscopy. METHODS:Thirty adult female small ear pigs in southern Yunnan province were selected.Anterior cruciate ligament reconstruction was performed on the left knee joint with the ipsilateral knee Achilles tendon(n=30 in the normal group),and anterior cruciate ligament reconstruction was performed on the right knee joint with the ipsilateral knee Achilles tendon combined with the internal relaxation and enhancement system(n=30 in the relaxation group).The autogenous right forelimb was used as the control group;the anterior cruciate ligament was exposed but not severed or surgically treated.At 12,24,and 48 weeks after surgery,10 animals were sacrificed,respectively.The left and right knee joint specimens were taken for gross morphological observation to evaluate the graft morphology.MAS score was used to evaluate the excellent and good rate of the ligament at each time point.Hematoxylin-eosin staining was used to evaluate the degree of ligament graft vascularization.Collagen fibers and nuclear morphology were observed,and nuclear morphology was scored.Ultrastructural remodeling was evaluated by scanning electron microscopy and transmission electron microscopy. RESULTS AND CONCLUSION:(1)The ligament healing shape of the relaxation group was better at various time points after surgery,and the excellent and good rate of MAS score was higher(P<0.05).Moreover,the relaxation group could obtain higher ligament vascularization score(P<0.05).(2)The arrangement of collagen bundles and fiber bundles in the two groups gradually tended to be orderly,and the transverse fiber connections between collagen gradually increased and thickened,suggesting that the strength and shape degree of the grafts were gradually improved,but the ligament remodeling in the relaxation group was always faster than that in the normal group at various time points after surgery.(3)The diameter,distribution density,and arrangement degree of collagen fibers in the relaxation group were better than those in the normal group at all time points,especially in the comparison of collagen fiber diameter between and within the relaxation group(P<0.05).

ObjectiveTo investigate the anti-inflammatory and antioxidant effects of baicalin for treating chronic obstructive pulmonary disease （COPD） in rats and decipher the molecular mechanisms via the nuclear factor-kappa B （NF-κB）/nuclear factor erythroid 2-related factor 2 （Nrf2） signaling pathway. MethodsSixty SPF-grade male Sprague-Dawley rats were randomly assigned into six groups： normal control， COPD model， low-dose baicalin， medium-dose baicalin， high-dose baicalin， and budesonide. The normal control group received no treatment， whereas COPD was modeled in other groups with a combined modeling approach involving intratracheal lipopolysaccharide instillation and passive cigarette smoke exposure. The model establishment was evaluated through behavioral observation combined with pathological examination. Hematoxylin-eosin （HE） staining was performed to assess histopathological changes in the lung. Serum levels of inflammatory cytokines ［interleukin （IL）-6， IL-8， IL-17， IL-22， tumor necrosis factor （TNF）-α， and transforming growth factor （TGF）-β）］， reactive oxygen species （ROS）， and vascular endothelial growth factor （VEGF） were quantified by enzyme-linked immunosorbent assay （ELISA）. Meanwhile， the levels of IL-6， IL-17， and IL-22 in the bronchoalveolar lavage fluid （BALF） and IL-10， IL-22， and TNF-α in the lung tissue were measured via ELISA. Immunohistochemistry （IHC） was employed to detect the expression of histone deacetylase 2 （HDAC2） and Nrf2. Western blot was performed to evaluate the expression of phosphoinositide 3-kinase （PI3K）， protein kinase B （Akt）， glucocorticoid receptor （GR）， NF-κB， HDAC2， and Nrf2 in the lung tissue. Additionally， real-time PCR was conducted to assess the mRNA levels of PI3K， Akt， HDAC2， Nrf2， GR， and NF-κB in the lung tissue. ResultsHE staining revealed that the airway mucosal epithelium in the COPD model group appeared extensive shedding， structural disorganization， and diffuse infiltration of inflammatory cells within the lumen. And goblet cells showed compensatory proliferation with pathological hypertrophy of mucus glands. In contrast， inflammatory infiltration and alveolar overdistension were significantly alleviated in the medium- and high-dose baicalin groups. The COPD model group exhibited mucus plug formation within the terminal bronchioles， along with fibrotic narrowing of the bronchial wall. Moreover， the smooth muscle bundles of the bronchial wall were hypertrophic， with concomitant collagen deposition. Progressive dissolution and rupture of alveolar septa were observed， leading to the formation of abnormally enlarged air-filled cavities. However， the bronchial wall structure was largely restored with only mild thickening of the smooth muscle layer in the baicalin groups. Compared with the COPD model group， the medium- and high-dose baicalin groups showed declined ROS and VEGF levels （P<0.05）， and all the baicalin groups presented lowered levels of IL-6， IL-8， IL-17， IL-22， TGF-β， and TNF-α and elevated level of IL-10 （P<0.05）. Baicalin upregulated the protein levels of HDAC2， Nrf2， GR， PI3K， and Akt， while suppressing the protein level of NF-κB （P<0.05）. Furthermore， baicalin increased the mRNA levels of Nrf2 and GR while down-regulating the mRNA level of NF-κB （P<0.05）. ConclusionBaicalin exerts anti-inflammatory and antioxidant effects by inhibiting the pro-inflammatory factor NF-κB while enhancing the expression of the anti-inflammatory factor HDAC2 and activating the antioxidant factor Nrf2， thereby alleviating the lung tissue damage in COPD rats. The therapeutic effects of baicalin may be closely associated with its regulatory role in the NF-κB/Nrf2 signaling pathway.

ObjectiveTo investigate the anti-inflammatory and antioxidant effects of baicalin for treating chronic obstructive pulmonary disease （COPD） in rats and decipher the molecular mechanisms via the nuclear factor-kappa B （NF-κB）/nuclear factor erythroid 2-related factor 2 （Nrf2） signaling pathway. MethodsSixty SPF-grade male Sprague-Dawley rats were randomly assigned into six groups： normal control， COPD model， low-dose baicalin， medium-dose baicalin， high-dose baicalin， and budesonide. The normal control group received no treatment， whereas COPD was modeled in other groups with a combined modeling approach involving intratracheal lipopolysaccharide instillation and passive cigarette smoke exposure. The model establishment was evaluated through behavioral observation combined with pathological examination. Hematoxylin-eosin （HE） staining was performed to assess histopathological changes in the lung. Serum levels of inflammatory cytokines ［interleukin （IL）-6， IL-8， IL-17， IL-22， tumor necrosis factor （TNF）-α， and transforming growth factor （TGF）-β）］， reactive oxygen species （ROS）， and vascular endothelial growth factor （VEGF） were quantified by enzyme-linked immunosorbent assay （ELISA）. Meanwhile， the levels of IL-6， IL-17， and IL-22 in the bronchoalveolar lavage fluid （BALF） and IL-10， IL-22， and TNF-α in the lung tissue were measured via ELISA. Immunohistochemistry （IHC） was employed to detect the expression of histone deacetylase 2 （HDAC2） and Nrf2. Western blot was performed to evaluate the expression of phosphoinositide 3-kinase （PI3K）， protein kinase B （Akt）， glucocorticoid receptor （GR）， NF-κB， HDAC2， and Nrf2 in the lung tissue. Additionally， real-time PCR was conducted to assess the mRNA levels of PI3K， Akt， HDAC2， Nrf2， GR， and NF-κB in the lung tissue. ResultsHE staining revealed that the airway mucosal epithelium in the COPD model group appeared extensive shedding， structural disorganization， and diffuse infiltration of inflammatory cells within the lumen. And goblet cells showed compensatory proliferation with pathological hypertrophy of mucus glands. In contrast， inflammatory infiltration and alveolar overdistension were significantly alleviated in the medium- and high-dose baicalin groups. The COPD model group exhibited mucus plug formation within the terminal bronchioles， along with fibrotic narrowing of the bronchial wall. Moreover， the smooth muscle bundles of the bronchial wall were hypertrophic， with concomitant collagen deposition. Progressive dissolution and rupture of alveolar septa were observed， leading to the formation of abnormally enlarged air-filled cavities. However， the bronchial wall structure was largely restored with only mild thickening of the smooth muscle layer in the baicalin groups. Compared with the COPD model group， the medium- and high-dose baicalin groups showed declined ROS and VEGF levels （P<0.05）， and all the baicalin groups presented lowered levels of IL-6， IL-8， IL-17， IL-22， TGF-β， and TNF-α and elevated level of IL-10 （P<0.05）. Baicalin upregulated the protein levels of HDAC2， Nrf2， GR， PI3K， and Akt， while suppressing the protein level of NF-κB （P<0.05）. Furthermore， baicalin increased the mRNA levels of Nrf2 and GR while down-regulating the mRNA level of NF-κB （P<0.05）. ConclusionBaicalin exerts anti-inflammatory and antioxidant effects by inhibiting the pro-inflammatory factor NF-κB while enhancing the expression of the anti-inflammatory factor HDAC2 and activating the antioxidant factor Nrf2， thereby alleviating the lung tissue damage in COPD rats. The therapeutic effects of baicalin may be closely associated with its regulatory role in the NF-κB/Nrf2 signaling pathway.

BACKGROUND:Currently,there have been studies on the regulatory mechanism of lncRNA\miRNA\mRNA co-expression network on the occurrence and development of osteoarthritis.Our research group has screened qualified NONHSAT248596.1 and miR-146a-5p through the database in the previous stage,but the corresponding in vivo experiments to verify the above regulatory mechanisms are still lacking. OBJECTIVE:To explore the role of NONHSAT248596.1 in regulating competitive endogenous RNA of miR-146a-5p in cartilage degeneration mediated by stromal cell derived factor type 1/chemokine receptor 4 axis in vivo. METHODS:The models of osteoarthritis were established in 36 New Zealand rabbits by injecting stromal cell derived factor 1 solution into the knee joint of the right hind limb.According to the random number table method,they were divided into four groups.lncRNA group,miRNA group,ceRNA group and control group were injected with lentivirus vector overexpressing NONHSAT248596.1,lentivirus vector overexpressing miR-146a-5p,lentivirus vector overexpressing miR-146a-5p+NONHSAT248596.1 and empty lentivirus vector into the molded knee joint,respectively.At 4,8 and 12 weeks of modeling,cartilage tissues and subchondral bone tissues of the knee joint were taken for relevant detection. RESULTS AND CONCLUSION:Hematoxylin-eosin staining and safranin fast green staining showed different degrees of degeneration in the four groups.At 4 weeks,the cartilage tissue of the lncRNA group showed swelling of chondrocytes,loss of cell polarity,destruction of extracellular matrix,surface erosion,fracture formation and partial or full layer loss of cartilage tissue.The degree of cartilage injury was gradually aggravated with time.The progression of articular cartilage inflammation in the miRNA group was the slowest among the four groups.qRT-PCR showed that at the same time point,mRNA expression levels of NONHSAT248596.1,chemokine receptor 4,matrix metalloproteinase 3,matrix metalloproteinase 9 and matrix metalloproteinase 13 in cartilage tissue of the lncRNA group were higher than those of the other three groups(P＜0.05).The mRNA expression levels of miR-146a-5p,aggrecan and type Ⅱ collagen were lower than those of the other three groups(P＜0.05).The mRNA expression levels of NONHSAT248596.1,chemokine receptor 4,matrix metalloproteinase 3,matrix metalloproteinase 9 and matrix metalloproteinase 13 in the miRNA group were lower than those in the ceRNA group and control group at 8 and 12 weeks after the model construction(P＜0.05).The mRNA expressions of miR-146a-5p,aggrecan and type Ⅱ collagen were higher than those of the ceRNA group and control group(P＜0.05).Western blot assay showed that at the same time point,the expression levels of aggrecan and type Ⅱ collagen in cartilage tissue of the lncRNA group were always lower than those of the other three groups(P＜0.05).The expression levels of aggrecan and type Ⅱ collagen in cartilage tissue of the miRNA group at 8 and 12 weeks after modeling were higher than those of the ceRNA group and control group(P＜0.05).The results showed that miR-146a-5p,as the target of NONHSAT248596.1,could be inhibited by the effect of its ceRNA.After acting on miR-146a-5p,NONHSAT248596.1 regulates the stromal cell derived factor type 1/chemokine receptor 4 axis to affect the expression of matrix metalloprotein,type Ⅱ collagen,and aggrecan in osteoarthritis chondrocytes,resulting in the degradation of extracellular matrix and the loss of proteoglycan.

Objective:To compare the clinical efficacies between arthroscopic anatomic single bundle reconstruction of posterior cruciate ligament (PCL) assisted by internal tension relieving technique combined with rapid rehabilitation and anatomic single bundle reconstruction combined with conventional rehabilitation in the treatment of PCL rupture.Methods:A retrospective cohort study was used to analyze the clinical data of 88 patients with PCL rupture admitted to First Affiliated Hospital of Kunming Medical University from September 2016 to September 2020. The patients included 65 males and 23 females, aged 18-55 years [(39.3±10.8)years]. Forty-four patients underwent arthroscopic anatomic single bundle reconstruction of PCL assisted by internal tension relieving technique combined with rapid rehabilitation therapy (tension-relieving group), and 44 patients underwent arthroscopic routine anatomic single bundle reconstruction of PCL combined with conventional rehabilitation (traditional group). The two groups were compared before and at 3, 12, and 24 months after surgery regarding the following items: International Knee Literature Committee (IKDC) score, Hospital for Special Surgery (HSS) score, Lysholm score, knee motion cycle (maximum stride length, minimum stride length, and stride frequency) and 6 kinematic indicators (angle of forward and back extension, angle of internal and external rotation, angle of internal and external rotation, up and down displacement, internal and external displacement, and forward and back displacement). The Marburger arthroscopy score (MAS) and Professor Ao Yingfang′s improved score by secondary arthroscopy were compared between the two groups at 12 months after surgery. The perioperative complications were observed.Results:All patients were followed for 24-36 months [(25.5±6.3)months]. In tension-relieving group and the traditional group, the values of IKDC score were (71.8±9.8)points and (68.5±6.5)points at 3 months after surgery, (87.6±6.0)points and (87.6±5.5)points at 12 months after surgery, and (95.5±3.1)points and (92.8±11.6)points at 24 months after surgery, respectively. The values were gradually increased, significantly higher than those before surgery [(48.1±16.9)points and (47.1±15.0)points] (all P<0.05). There were no significant differences between the two groups at each time point (all P>0.05). In tension-relieving group and the traditional group, the values of HSS score were (74.2±6.2)points and (68.4±9.5)points at 3 months after surgery, (91.9±5.4)points and (88.4±4.7)points at 12 months after surgery, and (97.1±2.0)points and (96.2±2.8)points at 24 months after surgery, respectively. The values of HSS score gradually increased, significantly higher than those before surgery [(57.5±17.7)points and (56.8±14.3)points] (all P<0.05). At 3 and 12 months after surgery, the values of HSS score in the tension-relieving group were significantly higher than those in the traditional group (all P<0.05), but others were not significantly different between the two groups (all P>0.05). In tension-relieving group and the traditional group, the values of Lysholm score were (74.2±14.9)points and (70.3±7.5)points at 3 months after surgery, (90.9±6.1)points and (88.7±4.7)points at 12 months after surgery, and (96.9±3.0)points and (96.3±2.8)points at 24 months after surgery, respectively. The values of Lysholm score were gradually increased, significantly higher than those before operation [(48.7±20.7)points and (48.2±19.9)points] (all P<0.05). There were no significant differences between the two groups at any time points (all P>0.05). At 3, 12, and 24 months after surgery, the motion cycle (maximum stride length, minimum stride length and stride frequency) and 6 kinematic indicators (angle of forward bending and backward extension, angle of internal and external rotation, angle of internal and external rotation, internal and external displacement, up and down displacement, and forward and backward displacement) of knee joint were significantly improved in both groups compared with those before surgery (all P<0.05). At 3, 12, and 24 months after surgery, the forward and backward displacement in the tension-relieving group was significantly decreased than that in the traditional group (all P<0.05), but others were not significantly different between the two groups (all P>0.05). The MAS was rated as excellent to good in 14 patients and fair to poor in 2, with the excellent and good rate of 87.5% (14/16) in the tension-relieving group, while the score was rated as excellent to good in 11 patients and fair to poor in 3, with the excellent and good rate of 78.6% (11/14) in the traditional group ( P>0.05). The Professor Ao Yingfang′s improved score was (10.6±1.5)points in the tension-relieving group, markedly higher than that in the traditional group [(9.6±2.3)points] ( P<0.05). No perioperative complications were observed. Conclusion:Compared with anatomic single bundle reconstruction combined with conventional rehabilitation, arthroscopic anatomic single bundle reconstruction of PCL assisted by internal tension relieving technique combined with rapid rehabilitation have higher subjective function score, better anteroposteric stability during knee movement, and better results of secondary microscopy.

OBJECTIVE: To investigate the feasibility of establishing an anterior cruciate ligament (ACL) reconstruction model using hamstring tendon autograft in cynomolgus monkeys. METHODS: Twelve healthy adult male cynomolgus monkeys, weighing 8-13 kg, were randomly divided into two groups ( n=6). In the experimental group, the ACL reconstruction model of the right lower limb was prepared by using a single bundle of hamstring tendon, and the ACL of the right lower limb was only cut off in the control group. The survival of animals in the two groups was observed after operation. Before operation and at 3, 6, and 12 months after operation, the knee range of motion, thigh circumference, and calf circumference of the two groups were measured; the anterior tibial translation D-value (ATTD) was measured by Ligs joint ligament digital body examination instrument under the loads of 13-20 N, respectively. At the same time, the experimental group underwent MRI examination to observe the graft morphology and the signal/ noise quotient (SNQ) was caculated. RESULTS: All animals survived to the end of the experiment. In the experimental group, the knee range of motion, thigh circumference, and calf circumference decreased first and then gradually increased after operation; the above indexes were significantly lower at 3 and 6 months after operation than before operation ( P<0.05), and no significant difference was found between pre-operation and 12 months after operation ( P>0.05). In the control group, there was no significant change in knee range of motion after operation, showing no significant difference between pre- and post-operation ( P>0.05), but the thigh circumference and calf circumference gradually significantly decreased with time ( P<0.05), and the difference was significant when compared with those before operation ( P<0.05). At 6 and 12 months after operation, the thigh circumference and calf circumference were significantly larger in the experimental group than in the control group ( P<0.05). At 3 and 6 months after operation, the knee range of motion was significantly smaller in the experimental group than in the control group ( P<0.05). Under the loading condition of 13-20 N, the ATTD in the experimental group increased first and then decreased after operation; and the ATTD significantly increased at 3, 6 months after operation when compared with the value before operation ( P<0.05). But there was no significant difference between the pre-operation and 12 months after operation ( P>0.05). There was no significant change in ATTD in the control group at 3, 6, and 12 months after operation ( P>0.05), and which were significantly higher than those before operation ( P<0.05). At each time point after operation, the ATTD was significantly smaller in the experimental group than in the control group under the same load ( P<0.05). The MRI examination of the experimental group showed that the ACL boundary gradually became clear after reconstruction and was covered by the synovial membrane. The SNQ at each time point after operation was significantly higher than that before operation, but gradually decreased with time, and the differences between time points were significant ( P<0.05). CONCLUSION The ACL reconstruction model in cynomolgus monkey with autogenous hamstring tendon transplantation was successfully established.
Animals ; Male ; Anterior Cruciate Ligament/surgery* ; Anterior Cruciate Ligament Injuries/surgery* ; Anterior Cruciate Ligament Reconstruction ; Hamstring Tendons/surgery* ; Knee Joint/surgery* ; Macaca fascicularis ; Transplantation, Autologous

Acute gastrointestinal dysfunction is a common and important complication of sepsis. As no exiting formal definition and classification of gastrointestinal dysfunction, most of the treatment strategies for gastrointestinal dysfunction are not based on clinical evidence, but on their own clinical experience. Experts of traditional Chinese medicine, integrated traditional Chinese and Western medicine and Western medicine from various disciplines in Shanghai are organized by the Shanghai Society of Integrated Traditional Chinese and Western Medicine and the Emergency Department Branch of Shanghai Physicians Association. After repeated discussion, literature search and formulation of the outline, we developed consensus on gastrointestinal dysfunction secondary to sepsis with integrating Traditional Chinese Medicine and Western medicine by consulting extensively on clinical experts in the fields of emergency medicine, gastroenterology, general surgery, infectious medicine and traditional Chinese medicine, and holding several expert forums and consultation meetings. This clinical expert consensus focused on acute gastrointestinal injury (AGI) classification and inducer of sepsis. In this consensus, the common symptoms, diagnosis, classifications, treatment strategies and suggestions of acute gastrointestinal injury or dysfunction secondary to sepsis were explored from the aspect of both Traditional Chinese Medicine and Western medicine.

Cadmium (Cd) is a common heavy metal in the environment. Cd²⁺ may penetrate the blood-brain barrier and produce neurotoxicity, thus inducing various neurodegenerative diseases. Celastrol is an effective component of Tripterygium wilfordii Hook. F., which has many pharmacological effects such as anti-cancer and anti-inflammatory. Here we explored the effect of celastrol on the corresponding neurotoxicity induced by Cd²⁺. Cell proliferation test, cell membrane integrity test, and cell morphology were observed to analyze the effect of Cd²⁺ on the viability of HMC3. The neurotoxicity of Cd²⁺ and the effect of celastrol on the corresponding neurotoxicity induced by Cd²⁺ were analyzed by nitric oxide (NO) test, lipid peroxidation (MDA) test, and Western blotting. When the concentration of Cd²⁺ reached 40 μmol/L, the inhibition rate of HMC3 cell proliferation was (57.17±8.23)% (P < 0.01, n=5), compared with the control group. The cell activity continued to reduce when the Cd²⁺ concentration further increased. When the concentration of Cd²⁺ was higher than 40 μmol/L, the cell membrane of HMC3 was significantly damaged, and the damage was dose-dependent. Upon increasing the Cd²⁺ concentration, the cell morphology began to change and the adhesion also became worse. Cd²⁺ significantly increased the amount of NO released by HMC3 cells, while celastrol effectively inhibited the NO release of HMC3 cells induced by Cd²⁺. Cd²⁺ greatly increased the release of MDA in HMC3 cells, and the level of MDA decreased rapidly upon the addition of 10^-7 mol/L celastrol. Cd²⁺ increased the expression of p-PI3K protein, and the levels of p-PI3K protein and p-AKT protein were inhibited by the addition of celastrol (10^‒7 mol/L, 10^‒6 mol/L), thus preventing cell apoptosis. In conclusion, celastrol inhibits Cd²⁺ induced microglial cytotoxicity and plays a neuroprotective role.
Anti-Inflammatory Agents/pharmacology* ; Apoptosis ; Cadmium/toxicity* ; Nitric Oxide/pharmacology* ; Pentacyclic Triterpenes ; Phosphatidylinositol 3-Kinases ; Proto-Oncogene Proteins c-akt/metabolism* ; Triterpenes/pharmacology*

ObjectiveBased on ultra performance liquid chromatography-quadrupole time-of-flight mass spectrometry （UPLC-Q-TOF/MS）， the changes of endogenous markers in rat plasma at the different stage， namely modeling and administration of Shenling Baizhusan （SLBZS）， and the mechanism of SLBZS in the treatment of ulcerative colitis （UC） were studied. MethodIn the modeling stage， rats were randomly divided into normal group， spleen deficiency with dampness retention-UC （SDDR-UC） and pure-UC （P-UC） model group. In the administration stage， SLBZS was given to the above two different model groups. After modeling and administration， rat plasma was collected and determined by UPLC-Q-TOF/MS. The mobile phase was 0.1% formic acid aqueous solution （A）-acetonitrile （B） for gradient elution （in positive ion mode：0-2 min， 99%A； 2-9 min， 99%-73%A； 9-10 min， 73%-44%A； 10-13 min， 44%-38%A； 13-19 min， 38%-28%A； 19-21 min， 28%-2%A； 21-23 min， 2%A； 23-25 min， 2%-10%A； 25-27 min， 10%-99%A； in negative ion mode：0-2 min， 85%A； 2-3 min， 85%-65%A； 3-5.5 min， 65%-44%A； 5.5-8 min， 44%-25%A； 8-10 min， 25%-2%A； 10-16 min， 2%-85%A）. The electrospray ionization （ESI） temperature was 120 ℃ under the positive and negative ion modes， and the acquisition range was 50-1 000. Partial least squares-discriminant analysis （PLS-DA） was used to analyze the changes of endogenous metabolites in the above two different model rats from the different stage. MetaboAnalyst 5.0 was used to analyze the metabolic pathways of these identified metabolites. ResultSixteen potential biomarkers were screened and identified in the modeling stage， among which 11 potential biomarkers were common in the two model rats， which mainly affected the primary bile acid biosynthesis pathway. Twenty-three potential biomarkers were screened and identified during the administration stage， among which 3 potential biomarkers were shared by the two model rats， and SDDR-UC and P-UC model rats had 11 and 9 potential biomarkers， respectively. It mainly affected 6 pathways such as purine metabolism， pentose phosphate pathway， pyrimidine metabolism， retinol metabolism， primary bile acid biosynthesis and steroid hormone synthesis. ConclusionThe primary bile acid biosynthesis pathway appears in the different stage of modeling and administration of UC， showing a dynamic change process. The therapeutic effect of SLBZS on SDDR-UC rats may be related to inhibiting the expression of nuclear transcription factor -κB （NF-κB） signaling pathway， activating farnesoid X receptor （FXR） and enhancing the expression of cytochrome P450.

Objective To investigate the serological and molecular identification of 2 rare B( A) blood groups. Methods The ABO blood groups of 2 samples from blood donors were detected by routine serological method. The genotype features was identified by PCR-sequence specific primer (PCR-SSP) and direct sequence analysis. Results The serological results for the 2 blood donors showed the characteristics of B(A) phenotype. The sample 1 was genotyped as BO2 subtype by PCR-SSP and direct sequencing showed B alleles in exon 7, presented nt640 A＞G mutation which was confirmed to be B(A)04/O02 genotype.The sample 2 was genotyped as BO1 sub-type by PCR-SSP and direct sequencing showed B alleles presented nt700 C＞G mutation in exon 7 which was confirmed to be B(A)02/O01 genotype. Conclusion The phenotype of the two samples should be B ( A ) and the genotypes should be rare B(A)04/O02 and B(A)02/O01.