ObjectiveTo investigate the effects of jatrorrhizine on endogenous metabolites and metabolic pathways in the mouse model of ulcerative colitis. MethodsThirty male C57BL/6J mice were randomly divided into the normal group， the model group， the low-dose and high-dose jatrorrhizine groups （0.04， 0.16 g·kg^-1）， and the mesalazine group （0.52 g·kg^-1）The mouse model of ulcerative colitis was established with 3% dextran sulfate sodium （DSS） and treated with different doses of jatrorrhizine by gavage. The changes in body weight， colon length， disease activity index （DAI）， and colonic histopathology were analyzed to evaluate the therapeutic effects of jatrorrhizine. UPLC-Q-TOF/MS was employed to determine the serum and fecal levels of metabolites in mice. Metabolomics methods were used to screen the differential metabolites， on the basis of which the potential therapeutic mechanism of jatrorrhizine on DSS-induced ulcerative colitis in mice was investigated. ResultsAfter intervention with jatrorrhizine， the model mice showed significantly decreased DAI（P<0.05，P<0.01）， recovered colon length，（P<0.05，P<0.01） and alleviated histopathology of the colon. The metabolomics study screened out 13 differential metabolites in the serum and 8 differential metabolites in the feces. The pathway enrichment analysis predicted three potential metabolic pathways： Biosynthesis of unsaturated fatty acids， phenylalanine， tyrosine and tryptophan biosynthesis， and phenylalanine metabolism. ConclusionJatrorrhizine may treat ulcerative colitis by regulating the biosynthesis and metabolism of amino acids and the synthesis of unsaturated fatty acids.

ObjectiveThis paper aims to explore the risk factors for chronic atrophic gastritis （CAG） with turbidity toxin accumulation syndrome and establish a prediction model. MethodsClinical data of 180 patients with CAG who participated in the "clinical study of Xianglian Huazhuo Particles blocking CAG cancer transformation" of Hebei Sheng Zhong Yi Yuan from July 2021 to March 2022 were collected. After confounding factors were controlled by propensity score matching， patients were divided into a training set （namely dev） and a validation set （namely vad） in a seven to three ratio. The risk factors for CAG with turbidity toxin accumulation syndrome in the training set were investigated by using univariate Logistic regression analysis and least absolute shrinkage and selection operator （namely Lasso） regression algorithms. Subsequently， a model， named model 1se， was developed by using the training set data to predict the risk factors for CAG with turbidity toxin accumulation syndrome. The accuracy of the prediction model was assessed by using various methods， including the receiver operating characteristic （ROC） curve， Hosmer-Lemeshow test （H-L）， calibration plot， and decision curve analysis （DCA）. ResultsAge， body mass index （BMI）， family history of cancer， job and life satisfaction， yellow and greasy fur with slippery pulse， and heavy body sensation were independent risk factors of the model. The prediction model showed excellent predictive value for both the training and validation sets. ConclusionThe established prediction model for CAG with turbidity toxin accumulation syndrome has high discrimination and excellent calibration， which could provide an excellent clinical basis for disease diagnosis and individualized treatment of patients.

ObjectiveThis paper aims to explore the risk factors for chronic atrophic gastritis （CAG） with turbidity toxin accumulation syndrome and establish a prediction model. MethodsClinical data of 180 patients with CAG who participated in the "clinical study of Xianglian Huazhuo Particles blocking CAG cancer transformation" of Hebei Sheng Zhong Yi Yuan from July 2021 to March 2022 were collected. After confounding factors were controlled by propensity score matching， patients were divided into a training set （namely dev） and a validation set （namely vad） in a seven to three ratio. The risk factors for CAG with turbidity toxin accumulation syndrome in the training set were investigated by using univariate Logistic regression analysis and least absolute shrinkage and selection operator （namely Lasso） regression algorithms. Subsequently， a model， named model 1se， was developed by using the training set data to predict the risk factors for CAG with turbidity toxin accumulation syndrome. The accuracy of the prediction model was assessed by using various methods， including the receiver operating characteristic （ROC） curve， Hosmer-Lemeshow test （H-L）， calibration plot， and decision curve analysis （DCA）. ResultsAge， body mass index （BMI）， family history of cancer， job and life satisfaction， yellow and greasy fur with slippery pulse， and heavy body sensation were independent risk factors of the model. The prediction model showed excellent predictive value for both the training and validation sets. ConclusionThe established prediction model for CAG with turbidity toxin accumulation syndrome has high discrimination and excellent calibration， which could provide an excellent clinical basis for disease diagnosis and individualized treatment of patients.

Objective To construct programmed cell death protein-ligand 1(PD-LI)^hi tolerogenic dendritic cell (tol-DC) derived from bone marrow of DA rats and identify its immunological function. Methods DA rat bone marrow cells were extracted, combined with recombinant mouse granulocyte macrophage colony-stimulating factor and recombinant mouse interleukin (IL)-4, and cultured for 6 days in vitro to induce the differentiation of bone marrow cells into immature dendritic cells (imDC). Lipopolysaccharide was used to stimulate cell maturation and cultured for 2 days to collect mature dendritic cells (mDC). PD-L1 lentiviral vector virus stock solution or equivalent dose lentiviral stock solution was added, and PD-L1^hitol-DC and Lv-imDC were collected after culture for 2 days. The morphology of PD-L1^hitol-DC was observed by inverted phase contrast microscope and transmission electron microscope. Real-time fluorescence quantitative reverse transcription polymerase chain reaction, Western blotting and flow cytometry were used to detect the expression level of specific markers on cell surface. CD8⁺T cells derived from Lewis rat spleen were co-cultured with imDC, mDC, Lv-imDC and PD-L1^hitol-DC, respectively. The levels of inflammatory factors in the supernatant of each group were detected by enzyme-linked immunosorbent assay. The apoptosis of T cells and the differentiation of regulatory T cells (Treg) in each group were analyzed by flow cytometry. Results The morphology of PD-L1^hitol-DC modified by PD-L1 gene was consistent with tol-DC characteristics, and the expression levels of CD80, CD86 and major histocompatibility complex (MHC) on the surface were low. After mixed culture with CD8⁺ T cells, the levels of IL-10 and transforming growth factor (TGF) -β1 in the supernatant of PD-L1^hitol-DC group were higher, the levels of tumor necrosis factor (TNF) -α and IL-17A were lower, and the apoptosis of T cells and Treg differentiation were increased. Conclusions Overexpression of PD-L1 through lentiviral vectors may successfully induce the construction of bone-marrow derived PD-L1^hitol-DC in DA rats, promote the secretion of anti-inflammatory factors and T cell apoptosis, induce the differentiation of Treg, and inhibit the immune response of allogeneic CD8⁺T cells, which provides experimental basis for the next organ transplantation immune tolerance study.

BACKGROUND: The choice of unicompartmental knee arthroplasty (UKA) vs . total knee arthroplasty (TKA) in the surgical treatment of knee osteoarthritis (KOA) remains controversial. This study aimed to perform a systematic review and meta-analysis of randomized controlled trials (RCTs) to compare the clinical results of UKA and TKA for treating unicompartmental KOA. METHODS: PubMed, Embase, and the Cochrane Library were systematically searched for articles published up to January 2, 2023. The literature was rigorously screened to include only RCTs comparing UKA and TKA for unicompartmental KOA. A systematic review and meta-analysis were performed to calculate the mean difference (MD), relative risk (RR), and 95% confidence interval (CI) according to the Cochrane standards. RESULTS: Thirteen publications involving 683 UKAs and 683 TKAs were analyzed. Except for one study with a follow-up period of 15 years, all outcome measures reported were within 5 years of follow-up. Meta-analysis showed better knee recovery (MD: 1.23; 95% CI: 1.01-1.45; P  <0.001), greater knee function (MD: 1.78; 95% CI: 0.34-3.22; P  = 0.020), less pain (MD: 0.75; 95% CI: 0.43-1.06; P  <0.001), and better health status (MD: 3.75; 95% CI: 0.81-6.69; P  = 0.010) after UKA than TKA. However, considering the minimal clinically important difference values for these variables, the findings were not clinically relevant. Moreover, UKA patients had fewer complications (RR: 0.59; 95% CI: 0.45-0.78; P  <0.001) and shorter hospital stays (MD: -0.89; 95% CI: -1.57 to -0.22; P  = 0.009) than did TKA patients. There were no statistically significant differences in terms of postoperative range of movement, revision, failure, operation time, and patient satisfaction. CONCLUSIONS In terms of clinical efficacy, there was no obvious advantage of UKA over TKA in the surgical treatment of knee OA when considering the minimal clinically important difference. The main advantage of UKA over TKA is that it leads to fewer complications and a shorter length of hospital stay. It is ideal to perform prospective studies with longer follow-up periods to fully evaluate the long-term efficacy and safety of the two procedures in the future.
Humans ; Arthroplasty, Replacement, Knee/methods* ; Osteoarthritis, Knee/surgery* ; Randomized Controlled Trials as Topic ; Treatment Outcome

Eleven sesquiterpenoids were isolated from the petroleum ether and ethyl acetate extracted fraction of 95% ethanol extract of fresh Centipeda minima by using modern chromatographic separation techniques such as silica gel, MCI, gel, and semi-preparative liquid chromatography. Their structures were identified using spectroscopy and nuclear magnetic resonance(NMR) calculation as minimin A(1), brevilin A(2), minimolide L(3), minimolide A(4), minimolide B(5), arnicolide D(6), microhelenin C(7), 2β-hydroxyl-2,3-dihydrogen-6-O-angeloylplenolin(8), 11α,13-dihydroarnifolin(9),(1S,2R,5R,6S,7S,8S,10R)-6-hydroxy-2-ethoxy-4-oxopseudoguai-11(13)-en-12,8-olide(10), and pulchellin-2-O-isovalerate(11), among which compound 1 was a new compound, and compounds 9-11 were isolated from Centipeda for the first time. The evaluation results of in vitro anti-inflammatory activity showed that compounds 1-11 possessed significant anti-inflammatory activity, with IC_(50) values ranging from(0.13±0.03) to(13.11±0.17) μmol·L~(-1).
Sesquiterpenes/pharmacology* ; Animals ; Asteraceae/chemistry* ; Mice ; Drugs, Chinese Herbal/pharmacology* ; Molecular Structure ; Magnetic Resonance Spectroscopy ; Macrophages/immunology*

In this study, serum metabolomics techniques and molecular biology methods were used to investigate the intervention effect of kaji-ichigoside F1 on chronic unpredictable mild stress(CUMS) depression mouse model and its mechanism. The CUMS depression mouse model was constructed, and the mice were divided into blank group, model group, escitalopram(ESC, 10 mg·kg~(-1)) group, and low-dose, medium-dose, and high-dose kaji-ichigoside F1 groups(1, 2, and 4 mg·kg~(-1)). CUMS modeling was performed on all mice except the blank group, and the cycle was four weeks. At the end of modelling, ESC and kaji-ichigoside F1 were administered by gavage once a day for 28 days. After the end of the administration, behavioral testing(sucrose preference test, open field test, forced swimming test, and tail suspension test) was conducted to evaluate the improvement of depression symptoms of different doses of kaji-ichigoside F1 on CUMS depression mouse model. The morphology of neurons and the number of Nissl bodies in the hippocampus were observed by Nissl staining. Metabolomics technique was used to analyze the changes in serum differential metabolites in mice. Protein expression levels of P2X7 purinergic receptor(P2X7R), adenosine A1 receptor(A1R), and adenosine receptor A2A(A2AR) in mouse hippocampus were detected by Western blot. The results showed that compared with that in the blank group, the body weight of mice in the model group was significantly decreased, and the sucrose preference rate was significantly decreased. The immobility time was significantly increased in the forced swimming and tail suspension tests, and the total moving distance was significantly decreased in the open field test. The number of Nissl bodies was significantly decreased, and the depression-like behavior and the number of Nissl bodies in the hippocampus of mice were significantly improved after administration of kaji-ichigoside F1. In the metabonomics analysis, the purine metabolism of serum after kaji-ichigoside F1 administration was involved in the metabolic passage of depression, and Western blot analysis verified the expression of P2X7R, A1R, and A2AR proteins in purine metabolic pathways. The results show that kaji-ichigoside F1 significantly decreases the expression of P2X7R and A2AR proteins in the hippocampus of CUMS model mice and increases the expression level of A1R proteins. It is suggested that kaji-ichigoside F1 may play an antidepressant role by regulating the expression of P2X7R, A1R, and A2AR proteins in the purine metabolism pathway.
Animals ; Mice ; Antidepressive Agents/administration & dosage* ; Metabolomics ; Depression/genetics* ; Male ; Drugs, Chinese Herbal/administration & dosage* ; Disease Models, Animal ; Hippocampus/metabolism* ; Behavior, Animal/drug effects* ; Humans

In order to solve the problems of difficult test, high cost and long cycle in the development of large-scale airborne negative pressure isolation system, the simulation analysis of negative pressure response characteristics is carried out around various aviation conditions such as aircraft ascending, leveling and descending, especially rapid decompression, based on the computational fluid dynamics (CFD) method. The results showed that the isolation cabin could achieve -50 Pa pressure difference environment and form a certain pressure gradient. The exhaust air volume reached the maximum value in the early stage of the aircraft's ascent, and gradually decreased with the increase of altitude until it was level flying. In the process of aircraft descent, the exhaust fan could theoretically maintain a pressure difference far below -50 Pa without working; Under the special condition of rapid pressure loss, it was difficult to deal with the rapid change of low pressure only by the exhaust fan, so it was necessary to design safety valve and other anti-leakage measures in the isolation cabin structure. Therefore, the initial stage of aircraft ascent is the key stage for the adjustment and control of the negative pressure isolation system. By controlling the exhaust air volume and adjusting parameters, it can adapt to the change of low pressure under normal flight conditions, form a relatively stable negative pressure environment, and meet the needs of biological control, isolation and transport.
Aircraft ; Computer Simulation ; Aviation/instrumentation* ; Humans ; Hydrodynamics ; Air Pressure ; Equipment Design ; Pressure

BACKGROUND:MiR-338-3p could inhibit osteoclast differentiation,and downregulation of receptor activator of nuclear factor-κB ligand level could promote bone formation.However,it is unclear whether miR-338-3p can affect the proliferation and apoptosis of alveolar bone osteoblasts by regulating the receptor activator of nuclear factor-κB ligand level. OBJECTIVE:To explore the effect and mechanism of miR-338-3p on proliferation and apoptosis of alveolar bone osteoblasts by targeting receptor activator of nuclear factor-κB ligand. METHODS:Human alveolar bone osteoblasts were isolated,transfected and treated with Wnt-C59(Wnt/β-catenin pathway inhibitor),and divided into transfection control group,miR-338-3p group,miR-338-3p+control group,miR-338-3p+receptor activator of nuclear factor-κB ligand group and miR-338-3p+Wnt-C59 group.The dual luciferase report experiment was used to verify the regulatory effect of miR-338-3p on receptor activator of nuclear factor-κB ligand.Cell counting kit-8 and 5-Ethynyl-2'-deoxyuridine staining were used to detect cell proliferation levels.Flow cytometry was used to detect cell cycle and apoptosis levels.RT-qPCR was used to detect miR-338-3p,receptor activator of nuclear factor-κB ligand,Wnt-3a,β-Catenin,glycogen synthase kinase-3β mRNA levels.Western blot was used to detect RANKL,proliferating cell nuclear antigen,Ki67,CyclinD1,B-cell lymphoma/leukemia-2,B-cell lymphoma-2 related X protein,Caspase3,Wnt-3a,β-catenin,glycogen synthase kinase-3β protein levels. RESULTS AND CONCLUSION:miR-338-3p could target the regulation of receptor activator of nuclear factor-κB ligand.After overexpression of miR-338-3p,cell survival rate,5-Ethynyl-2'-deoxyuridine positive cell rate,proportion of S-phase cells were increased,and apoptosis rate was decreased.The mRNA and protein levels of miR-338-3p,proliferating cell nuclear antigen,Ki67,CyclinD1,B-cell lymphoma/leukemia-2,Wnt-3a,and β-catenin were increased,while the mRNA and protein levels of B-cell lymphoma-2 related X protein,Caspase3 protein,receptor activator of nuclear factor-κB ligand,and glycogen synthase kinase-3β were decreased(all P<0.05).Overexpression of receptor activator of nuclear factor-κB ligand or Wnt-C59 could weaken the effects of overexpression of miR-338-3p on cell proliferation and apoptosis(all P<0.05).Overall,miR-338-3p promotes alveolar bone osteoblast proliferation and inhibits apoptosis by targeting receptor activator of nuclear factor-κB ligand,which may act through activation of the Wnt/β-catenin signaling pathway.

The Streptococcus suis meningitis patients often accompany with visual and hearing impairment,and their life quality is affected seriously after recovery.Our department admitted a 59-year-old male patient.The patient presented headache accompanied by fever,followed by decreased vision acuity in both eyes and reduced hearing in the right ear.The patient was alerted and oriented,with only light sensation in both eyes and reduced hearing in both ears(more pronounced on the right side).The neck strength was 3 horizontal fingers,and Kernig sign was positive.Magnetic resonance imaging(MRI)head scan showed patchy abnormal signals in the white matter of the right frontal lobe,while further enhanced MRI scan did not reveal any abnormal signals.The cerebrospinal fluid appeared slightly yellow and turbid color with blood droplets at the initial drip,and the total number of leukocytes and protein level were significantly increased.The glucose and chloride levels were decreased with the multinucleated cells accounting for 79％of the cellular components.The cerebrospinal fluid IgG level was 82.25 mg·L-1.Blood culture yielded Streptococcus suis as the causative pathogen.Metagenomic next generation sequencing(mNGS)in cerebrospinal fluid indicated Gram-positive bacteria,with 7 001 Streptococcus suis sequences detected.The patient was diagnosed with Streptococcus suis meningitis and treated with anti-infective therapy complemented by hormone and symptomatic treatment.Follow-up interviews at 6 and 18 months post-discharge revealed a satisfactory recovery of visual acuity,while the hearing did not improve significantly compared to at the time of discharge.In the patients with a history of exposure with sick or dead pigs who develop signs of meningitis accompanied by simultaneous involvement of other organs such as eyes and ears,Streptococcus suis meningitis should be considered and empirical anti-infective treatment should be provided as soon as possible.Blood culture and mNGS for definitive diagnosis should be conducted promptly.Combined application of Streptococcus suis-sensitive antibiotics and dexamethasone may help improve hearing impairments in these patients.