Objective To observe the multi-system toxicity of Tripterygium glycosides tablets in rats with type Ⅱ collagen-induced arthritis(CIA).Methods Healthy SD rats were randomly divided into normal group,model group and experimental group,with 10 rats in each group.In addition to the normal group,the other groups were established collagen-induced arthritis model.After the first immunization,the normal group and the model group were given an equal volume of 0.3％sodium carboxymethyl cellulose solution,and the experimental group was given 72 mg·kg-1·d-1 Tripterygium glycosides solution,once a day for 6 weeks.On the 42 nd day,the blood routine of each group was detected and the organ index was calculated.The levels of liver,kidney function and sex hormones in rats were detected by enzyme-linked immunosorbent assay.The histopathological changes of liver,kidney,ovary and testis were observed by hematoxylin-eosin(HE)staining.Results The testicular indexes of the normal group,the model group and the experimental group were(0.81±0.05)％,(0.97±0.06)％and(0.81±0.12)％;the estradiol contents were(63.90±16.19),(55.42±7.23)and(40.04±5.97)pg·mL-1;the testosterone contents were(1 290.96±257.94),(1 198.43±190.77)and(912.62±61.72)pg·mL-1,respectively.There were statistically significant differences in the above indexes between the model group and the experimental group(P＜0.01,P＜0.05).HE pathological results showed that Tripterygium glycosides tablets could cause abnormal histopathological changes of ovary and testis in CIA model rats.Conclusion Continuous administration of 8-fold clinical equivalent dose of Tripterygium glycosides tablets for 6 weeks can cause damage to the reproductive system of CIA rats.

Objective To evaluate the characteristics of the mass balance and pharmacokinetics of[14 C]birociclib in Chinese male healthy volunteers after a single oral administration.Methods This study used a 14 C labeled method to investigate the mass balance and biological transformation of birociclib in human.Subjects were given a single oral dose of 360 mg/50 pCi of[14 C]birociclib suspension after meals.The blood,urine,and fecal samples were collected at specified time points/intervals after administration.The radiation levels of 14 C labeled birociclib-related compounds in the blood,plasma,urine,and feces were analyzed using liquid scintillation counting.In addition,a combination of high-performance liquid chromatography and on-line/off-line isotope detectors was used to obtain radioactive isotope metabolite spectra of plasma,urine,and fecal samples,and high-resolution mass spectrometry was used to identify the main metabolites.Results A total of 6 healthy male subjects were enrolled in this study.The median peak time of radioactive components in plasma was 5.00 h and the average terminal elimination half-life was 43.70 h after administration.The radioactive components were basically excreted and cleared from the body within 288.00 hours after administration,and average cumulative recovery rate of radioactive drugs was(94.10±8.19)％.The radioactive drugs were mainly excreted through feces,accounting for(84.60±7.10)％of the dose of radioactive drugs administered.Urine was the secondary excretory pathway,accounting for 9.41％of the dose of radioactive drugs administered.Metabolic analysis indicated that the prototype drug was the main radioactive components in plasma samples.The main metabolites in plasma were RM4(XZP-5286),RM6(XZP-3584),and RM7(XZP-5736).The drugs were mainly cleared from the body in the form of prototype drugs and metabolites.In addition to prototype drugs,a total of 9 metabolites were identified and analyzed in plasma,urine,and fecal samples,all of which were phase 1 metabolites.The main metabolic and clearance pathways of drugs in the body were deethylation,diisopropylat ion,oxidation,etc.Conclusion After a single oral administration of[14C]birociclib suspension to healthy subjects,it was mainly cleared from the body in the form of prototype drugs and metabolites,with feces as the main excretory pathway and urine as the secondary excretory pathway.Drugs mainly undergo metabolic reactions in the body,such as deethylation,diisopropylation,and oxidation.The subjects were well tolerance after administration.

Objective This study aimed to evaluate whether the onset of the plateau phase of slow hepatitis B surface antigen decline in patients with chronic hepatitis B treated with intermittent interferon therapy is related to the frequency of dendritic cell subsets and expression of the costimulatory molecules CD40,CD80,CD83,and CD86. Method This was a cross-sectional study in which patients were divided into a natural history group(namely NH group),a long-term oral nucleoside analogs treatment group(namely NA group),and a plateau-arriving group(namely P group).The percentage of plasmacytoid dendritic cell and myeloid dendritic cell subsets in peripheral blood lymphocytes and monocytes and the mean fluorescence intensity of their surface costimulatory molecules were detected using a flow cytometer. Results In total,143 patients were enrolled(NH group,n = 49;NA group,n = 47;P group,n = 47).The results demonstrated that CD141/CD1c double negative myeloid dendritic cell(DNmDC)/lymphocytes and monocytes(%)in P group(0.041[0.024,0.069])was significantly lower than that in NH group(0.270[0.135,0.407])and NA group(0.273[0.150,0.443]),and CD86 mean fluorescence intensity of DNmDCs in P group(1832.0[1484.0,2793.0])was significantly lower than that in NH group(4316.0[2958.0,5169.0])and NA group(3299.0[2534.0,4371.0]),Adjusted P all<0.001. Conclusion Reduced DNmDCs and impaired maturation may be associated with the onset of the plateau phase during intermittent interferon therapy in patients with chronic hepatitis B.

Objective To explore characteristics of clinical parameters and cytokines in patients with drug-induced liver injury(DILI)caused by different drugs and their correlation with clinical indicators. Method The study was conducted on patients who were up to Review of Uncertainties in Confidence Assessment for Medical Tests(RUCAM)scoring criteria and clinically diagnosed with DILI.Based on Chinese herbal medicine,cardiovascular drugs,non-steroidal anti-inflammatory drugs(NSAIDs),anti-infective drugs,and other drugs,patients were divided into five groups.Cytokines were measured by Luminex technology.Baseline characteristics of clinical biochemical indicators and cytokines in DILI patients and their correlation were analyzed. Results 73 patients were enrolled.Age among five groups was statistically different(P=0.032).Alanine aminotransferase(ALT)(P=0.033)and aspartate aminotransferase(AST)(P=0.007)in NSAIDs group were higher than those in chinese herbal medicine group.Interleukin-6(IL-6)and tumor necrosis factor alpha(TNF-α)in patients with Chinese herbal medicine(IL-6:P<0.001;TNF-α:P<0.001)and cardiovascular medicine(IL-6:P=0.020;TNF-α:P=0.001)were lower than those in NSAIDs group.There was a positive correlation between ALT(r=0.697,P=0.025),AST(r=0.721,P=0.019),and IL-6 in NSAIDs group. Conclusion Older age may be more prone to DILI.Patients with NSAIDs have more severe liver damage in early stages of DILI,TNF-α and IL-6 may partake the inflammatory process of DILI.

Analyze the changes in phenolic components and gene expression profiles of Tetrastigma hemsleyanum leaves with supplemental blue light, and screen differentially expressed genes related to phenolic metabolism, providing a basis for improving the quality of T. hemsleyanum leaves. Using the leaves of T. hemsleyanum under supplemental blue light and visible light as research materials, the content of phenolic components such as neochlorogenic acid, chlorogenic acid, and 3-O-coumaroyl quinic acid was significantly increased by supplemental blue light. A total of 102 949 unigenes were obtained from the transcriptome, including 14 564 differentially expressed unigenes. They can be divided into 52 subclasses by gene ontology (GO) function, kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analysis showed that these differentially expressed unigenes were significantly enriched in phenolic metabolic pathways such as phenylpropane biosynthesis, flavonoid biosynthesis and isoflavone biosynthesis. A total of 63 differentially expressed unigenes were identified in the pathways related to the biosynthesis of phenolic cpmponents, including 19 key enzymes such as phenylalanine ammonia-lyase (PAL), cinnamyl-alcohol dehydrogenase (CAD), flavonol synthase (FLS), and so on. This study greatly enriched the genetic data information of T. hemsleyanum and laid a foundation for analyzing the mechanism of blue light promoting the biosynthesis of phenols and molecular breeding of T. hemsleyanum.

In this study, doxorubicin (DOX) was used as the model drug, new indocyanine green (IR820) as the photosensitizer, and temperature sensitive liposomes (TSL) as the carrier. H460-NCI photoheat-sensitive liposomes coated with cell membrane of human cell lung cancer (DOX-IR820-TSL@CCM) for highly effective multi-pathway tumor targeting in chemical-photothermal therapy and photodynamic therapy. DOX-IR820-TSL was prepared by reverse evaporation, cancer cell membrane (CCM) was prepared by lysis, crushing and centrifugation, and DOX-IR820-TSL@CCM was prepared by nanomembrane extrusion. The drug-loading conditions of DOX-IR820-TSL were finally determined: the ratio of organic phase to aqueous phase was 4.02, the dosage of dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) was 10.04 mg, and the lipid ratio was 0.12, and the significant phase transition temperature (T_m) of DOX-IR820-TSL was 43.05 ℃. The average particle size of DOX-IR820-TSL@CCM was 153.4 nm, the PDI was 0.279, and the zeta potential was -26.2 mV. The transmission electron microscope (TEM) image shows a homogeneous spherical structure and a translucent film layer. Under near-infrared irradiation, the drug release rate reaches 63.98%, which has adjustable photothermal conversion capacity and the ability to generate reactive oxygen species. Through SDS-PAGE electrophoresis, Western blot, cytotoxicity experiments and cell uptake experiments, it was proved that the design of cell membrane coating can well retain CD47, N-cadherin, CD44, CD326 and other related functional proteins, so that DOX-IR820-TSL@CCM has good immune evasion, homologous adhesion and homologous targeting. In this paper, DOX-IR820-TSL@CCM with camouflage properties and tumor targeting properties were successfully prepared, which can be used as a promising synergistic therapeutic diagnostic platform for future lung cancer treatment. All animal research programs have been approved by the Animal Ethics Committee of Heilongjiang University of Chinese Medicine (number: 2022121011).

Electrochemiluminescence(ECL)refers to the process of luminescence triggered by high-energy electron transfer between intermediate products during the oxidation-reduction reaction on the electrode surface.In the co-reactants involved ECL process,the presence of co-reaction accelerators can effectively catalyze the decomposition of co-reactants,leading to the generation of abundant free radical intermediates,thereby significantly enhancing the ECL signals.This plays a critical role in constructing simple,sensitive,and efficient ECL sensing platforms.This review focused on the novel co-reaction accelerators developed in recent years.Based on different types of co-reaction accelerator materials,including single atom catalysts,metal-based nanomaterials,polymers and other materials,the ECL reaction process and signal enhancement mechanisms,as well as their relevant applications in constructing ECL sensing platforms,were elucidated.Furthermore,the current research challenges and development prospect of co-reaction accelerators were also discussed.

Intramedullary needle(IMN)has the advantages of high healing rate and low incidence of complications in treatment of tibial fracture,and has become one of the most commonly used fixation methods for the treatment of tibial fracture.However,due to the patient's own factors,fracture location and fracture type,infection and surgical treatment,bone nonunion after IMN still occurs in clinic.Bone nonunion leads to the increase of medical cost and prolonged the hospitalization time of patients,which causes great pain to patients,and also brings great challenges to the treatment of orthopedic surgeons.Therefore,this paper reviews the influencing factors of bone nonunion after IMN for tibial fracture,in order to provide reference for clinical treatment.

Objective To compare the effects of different dose prediction models of sufentanil in elderly hip arthroplasty with ultrasound-guided bow tie fascia iliac block.Methods A total of 90 elderly patients who underwent ultrasound-guided bow tie fascia iliac during hip arthroplasty in our hospital from June 2018 to June 2022 were selected.The dose of sufentanil was determined by a linear regression(ALR),multiple linear regression(MLR)or deep belief networks(DBN).Patients were randomly divided into the ALR group,the MLR group and the DBN group,with 30 cases in each group.The analgesic effect,hemodynamic index,inflammatory factor level and surgical index were compared among all groups.Kaplan-Meier method was used to analyze the incidence of hip infection 2 weeks after surgery in each group.Results There was no significant difference in the gender,age,body weight,American Society of Anesthesiologists(ASA)classification or complications among all groups(P>0.05).The Harris score 24 hours after surgery and duration of sensory block in the DBN group were higher/longer than those in the ALR group,numerical rating scale(NRS)score 24 hours after surgery,mean arterial pressure(MAP)and heart rate(HR)at the beginning of surgery and 30 minutes after surgery,levels of interleukin-17(IL-17)and tumor necrosis factor-α(TNF-α)24 hours after surgery,onset time of sensory block,and number of patient controlled analgesia(PCA)compression were lower/earlier/less than those in the ALR group,the modified observer's assessment of alertness/sedation scale(OAA/S)score 24 hours after surgery was significantly lower than those in the ALR group and the MLR group,with statistically significant differences(P<0.05).Harris score 24 hours after surgery and duration of sensory block in the MLR group were higher/longer than those in the ALR group,modified OAA/S score 12 hours after surgery,MAP 30 minutes after surgery,levels of IL-17 and TNF-α 24 hours after surgery,onset time of sensory block,and the number of PCA compressions were lower/longer/less than those in the ALR group,with statistically significant differences(P<0.05).Kaplan-Meier analysis showed that there were significant differences in the incidences of hip infection 2 weeks after surgery among all groups(P<0.05),and there were significant differences in the incidences of hip infection 2 weeks after surgery between the ALR group and the DBN group(P<0.05).Conclusion The effectiveness of calculating the dose of sufentanil using the MLR and DBN in elderly hip arthroplasty with bow tie fascia iliac block is better than that of ALR,and the advantage of DBN is more obvious.

Objective To study the composition,abundance,and functional profiles of the intestinal microbiota in infants and young children with Kawasaki disease(KD)during the acute phase,and to explore the potential role of intestinal microbiota in the pathogenesis of KD.Methods Six children aged 0-3 years with acute KD admitted to the Department of Cardiology,Children's Hospital Affiliated to Capital Institute of Pediatrics from July to October 2021 were prospectively included as the KD group.Six age-and sex-matched healthy children who underwent physical examinations at the hospital during the same period were selected as the healthy control group.Metagenomics sequencing was used to detect and compare the differences in the microflora structure and functional profiles of fecal samples between the two groups.Results There were significant differences in the structural composition and diversity of intestinal microbiota between the two groups(P<0.05).Compared with the healthy control group,the abundance of Listeria_monocytogenes(family Listeriaceae and genus Listeria),Bifidobacterium_rousetti,Enterococcus_avium,and Enterococcus_hirae was significantly higher in the intestinal microbiota in the KD group(|LDA|>2.0,P<0.05).The steroid degradation and apoptosis pathways were significantly upregulated in the KD group compared with the healthy control group,while the Bacterial_secretion_system,Sulfur_metabolism,Butanoate_metabolism,Benzoate_degradation,β-alanine metabolism,and α-linolenic acid pathways were significantly downregulated(|LDA|>2,P<0.05).Conclusions There are significant differences in the structure and diversity of intestinal microbiota between children aged 0-3 years with acute KD and healthy children,suggesting that disturbances in intestinal microbiota occur during the acute phase of KD.In particular,Listeria_monocytogenes,Enterococcus_avium,and Enterococcus_hirae may be involved in the pathogenesis of KD through steroid degradation and apoptosis pathways.