AIM:Bone morphogenetic protein 7(BMP7)reduces the expression of Yes-related protein 1(YAP1)by down-regulating Ajuba level and decreasing extracellular matrix(ECM)deposition.This study aimed to inves-tigate the influence of these factors on modifying the degree of renal fibrosis in rats with diabetic nephropathy.METH-ODS:Eighteen Sprague-Dawley(SD)rats were randomly divided into three groups:the normal control(NC)group,the diabetes mellitus(DM)group,and the DM group treated with BMP7 overexpressing adeno-associated virus(DM+rAAV-BMP7).Each group consisted of six rats.Diabetic kidney disease(DKD)was established in the DM and DM+rAAV-BMP7 groups by injecting 55 mg/kg streptozotocin(STZ)via the tail vein.NRK-52E cells were divided into three groups:the normal glucose(NG)group,the high glucose(HG)group,and the high glucose group treated with recombinant hu-man BMP7(HG+rhBMP7)group.Pathological changes in renal tissues were observed using hematoxylin and eosin(HE)and Sirius red staining.Immunohistochemical staining was performed to examine the expression sites of Ajuba and YAP1 in the renal cortex.Western blot analysis was conducted to determine the expression levels of BMP7,Ajuba,YAP1,colla-gen type Ⅲ(Col-Ⅲ),and fibronectin(FN)in the rat renal cortex and NRK-52E cells.RT-qPCR was used to measure the mRNA levels of Ajuba and YAP1 in the rat renal cortex.RESULTS:Biochemical indices revealed significantly ele-vated levels of blood glucose,serum creatinine,triglycerides,total cholesterol,and 24-hour urinary protein in the DM group compared to the NC group(P<0.05).In the DM+rAAV-BMP7 group,the levels of serum creatinine,24-hour uri-nary protein,triglycerides,and total cholesterol were lower than those in the DM group(P<0.05).Pathological staining demonstrated that the renal interstitium of the DM group exhibited inflammatory cell infiltration,fibrous tissue,collagen fi-ber deposition,disordered renal tubule arrangement,atrophy,and vacuolar degeneration,which were ameliorated in the DM+rAAV-BMP7 group.Immunohistochemistry revealed that Ajuba and YAP1 were mainly expressed in the cytoplasm and nucleus,with high expression in the cytoplasm of the DM group,which was significantly decreased in the DM+rAAV-BMP7 group.Western blot results indicated that the protein levels of FN,Col-Ⅲ,Ajuba,and YAP1 were up-regulated in the DM and the HG groups(P<0.05),but significantly down-regulated in the DM+rAAV-BMP7 group(P<0.05).RT-qP-CR results demonstrated that the mRNA levels of Ajuba and YAP1 were higher in the DM group and significantly lower in the DM+rAAV-BMP7 group(P<0.05).CONCLUSION:The overexpression of BMP7 can ameliorate renal fibrosis in rats with DKD.This effect is likely mediated by the down-regulation of Ajuba,reduction of YAP1 expression,and subse-quent inhibition of ECM deposition.

Objectives To understand the quality status of disinfection products in the market in Shaanxi Province, and to provide a basis for taking targeted management measures. Methods From 2020 to 2023, in accordance with the national disinfection product management regulations and standards, the physicochemical and microbial tests of disinfection products in Shaanxi Province were carried out through supervised sampling, and the test results were analyzed according to the active ingredients, illegal addition, stability, and bactericidal or bacteriostatic performance. Results The overall qualification rate of the active ingredient content of disinfectants sampled in Shaanxi Province was 90.48%, with the lowest qualification rate in 2023 (84.38%). The overall qualification rate of quantitative sterilization test of disinfectants was 90.12%, showing a decreasing trend year by year (P=0.272). The overall qualification rate of anti-bacterial products was 88.59%, and the bactericidal test results of 20 antibacterial products were all qualified. The overall qualification rate of bacteriostatic performance testing for bacteriostatic products was 86.17%, with the pass rate of bacteriostatic product germicidal efficacy testing of different components in descending order being quaternary ammonium salt/silver ion > guanidine > others > lysozyme, and there was statistically significant difference (P=0.004). The detection rate of illegal additives in antimicrobial products was 7.07%, with the main detection indicators being miconazole nitrate, clobetasol propionate, and dexamethasone acetate. Conclusion The qualified rate of disinfection products in Shaanxi Province is relatively high, but there is a downward trend. It is necessary to continue to strengthen the daily supervision and product testing of disinfection product manufacturers, and promote the continuous improvement of disinfection product quality.

Benign anastomotic stenosis remains a common complication after bilojejunal anastomosis. Its pathogenesis includes the histology of bile duct, bile erosion, and inappropriate choice of surgical anastomosis or suture materials. Biliojejunal anastomotic stenosis can be determined preoperatively by MRCP, CT, and three-dimensional image reconstruction. Surgery remains treatment of choice for most cases, including surgical reconstruction and minimally invasive treatment, while the incidence of restenosis, residual stone, and reoperation is still high. Surgeons are still in search of optimal treatment modality to avoid anastomotic stenosis. In this article, we review the literature and summarize the latest clinical progress in the diagnosis and treatment of biliojejunal anastomotic stenosis combined with hepatic ductal stones.

Objective:To explore the role and molecular mechanism of Shikonin(SKN) in inhibiting the growth of anaplastic thyroid carcinoma(ATC) cells.Methods:The effect of SKN on ferroptosis in ATC cell lines CAL-62 was detected by flow cytometry; the expression levels of NF-κB, ferroptosis-related genes glutathione peroxidase 4(GPX4) and selenoprotein thioredoxin reductase 1(TXNRD1), glucose metabolism-related genes pyruvate kinase isoform 2(PKM2) and glucose transporter protein 1(GLUT1) were detected by Western blotting; real-time fluorescence quantitative(qPCR) to detect changes in the expression levels of GPX4, PKM2 and GLUT1; reactive oxygen species(ROS) fluorescent probe to detect changes in intracellular ROS positivity; glucose and lactic acid assay kit to detect the levels of glucose, the raw material of glucose metabolism(GLU), and lactate(LD), the product of glucose metabolism; and establishment of a subcutaneous tumour model in BALB/c nude mice to analyse the inhibitory effect of SKN on ATC in vivo.Results:Compared to the control group, after SKN treatment, the protein expression levels of NF-κB, GPX4, TXNRD1, GLUT1, and PKM2 in CAL-62 cells decreased( P=0.004, P=0.012, P=0.043, P=0.001, P=0.018); the mRNA expression of GPX4, GLUT1, and PKM2 also decreased( P<0.001, P=0.029, P<0.001). Additionally, ROS production increased( P=0.041). After treatment with the ferroptosis inhibitor Liproxstatin-1(L-1), the proportion of cell death was reversed to a certain extent, and there was no statistically significant difference in cell death proportion after L-1 treatment. Intracellular ferroptosis occurred( P<0.001), with reduced levels of glutamate(GLU) uptake and lipid peroxidation(LD) generation( P<0.001). SKN inhibited ATC tumor growth in vivo( P=0.016). Conclusion:SKN promotes intracellular ferroptosis in ATC cells, inhibits glycolysis and glucose uptake, and suppresses ATC cell growth.

Kidney is a highly energy-demanding organ rich in mitochondria. Numerous studies have indicated that mitochondria play a crucial role in maintaining normal kidney function and in the pathogenesis of various kidney diseases. Mitochondrial DNA is the exclusive genome of mitochondria. Damage to mtDNA not only leads to mitochondrial dysfunction and degradation of mitochondrial quality, but also acts as an endogenous inflammatory molecule, activating various inflammatory pathways, which contribute to cellular damage and the progression of kidney diseases. This article reviews the mechanisms of mitochondrial DNA damage and its significant role in triggering inflammatory injury in kidney diseases. Additionally, it summarizes the current research progress on various intervention strategies targeting this type of damage.

Live biotherapeutic products (LBPs) refer to the living bacteria derived from human body intestinal gut or in nature that can be used to treat the human disease. However, the naturally screened living bacteria have some disadvantages, such as deficient therapeutic effect and great divergence, which fall short of the personalized diagnosis and treatment needs. In recent years, with the development of synthetic biology, researchers have designed and constructed several engineered strains that can respond to external complex environmental signals, which speeded up the process of development and application of LBPs. Recombinant LBPs modified by gene editing can have therapeutic effect on specific diseases. Inherited metabolic disease is a type of disease that causes a series of clinical symptoms due to the genetic defect of some enzymes in the body, which may cause abnormal metabolism the corresponding metabolites. Therefore, the use of synthetic biology to design LBPs targeting specific defective enzymes will be promising for the treatment of inherited metabolic defects in the future. This review summarizes the clinic applications of LBPs and its potential for the treatment of inherited metabolic defects.
Humans ; Bacteria/genetics* ; Gene Editing ; Metabolic Diseases/therapy*

Objective:To compare the clinical efficacy and safety of ledipasvir/sofosbuvir (LDV/SOF) and elbasvir/grazoprevir (EBR/GZR) in treatment of patients with chronic hepatitis C (CHC).Methods:The clinical data of 143 patients with genotype 1b CHC treated in Huzhou Central Hospital from January 2020 to December 2021 were retrospectively analyzed, including 74 cases treated with LDV/SOF and 69 cases treated with EBR/GZR. The virological response after 4 and 12 weeks of treatment and 12wk after drug withdrawal was determined; and the serological and liver inflammation indexes before and after treatment in two groups were compared. SPSS 25.0 software was used for statistical analysis of the data.Results:The virological response rates of the LDV/SOF group and EBR/GZR group were 97.30% and 98.55%, 98.65% and 100.00%, 97.30% and 98.55% after 4 and 12 weeks of treatment and 12 weeks after the end of treatment, respectively (all P > 0.05). At the end of treatment, the liver inflammation indexes ALT, AST and GGT in the two groups were significantly lower than the baseline levels ( Z=-7.470 and -6.974, -9.757 and -6.832, -3.578 and -4.054, P<0.01). Adverse reactions in both groups were mild, and no serious adverse events occurred. Conclusion:Both LDV/SOF and EBR/GZR have good clinical efficacy in the treatment of genotype 1b CHC patients. And the patients are well tolerated.

[摘 要] 目的：探讨干扰B7-H4表达对乳腺癌细胞增殖、凋亡、周期以及相关下游分子表达的影响。方法：利用脂质体转染技术分别将特异性靶向B7-H4的siRNA（siB7-H4）及其阴性对照（siNC）转染至对数生长期的乳腺癌T47D和MCF-7细胞，分别命名为T47D-siB7-H4、T47D-siNC、MCF-7-siB7-H4和MCF-7-siNC组。用qPCR法和WB法验证siRNA干扰效果及其对细胞周期分子cyclin D1表达的影响，CCK-8法和FCM分别检测干扰B7-H4表达对T47D和MCF-7细胞增殖、周期和凋亡的影响，qPCR法检测B7-H4干扰对E2F家族相关转录因子表达的影响。结果：成功构建干扰B7-H4表达的乳腺癌T47D和MCF-7细胞。与T47D-siNC和MCF-7-siNC组相比，T47D-siB7-H4和MCF-7-siB7-H4组细胞中B7-H4 mRNA和蛋白表达水平均显著降低、细胞增殖能力显著降低（均P<0.01），并伴有G1/S期细胞周期阻滞以及cyclin D1表达下调（均P<0.01），但细胞凋亡率差异无统计学意义（均P>0.05）。与T47D-siNC相比，干扰B7-H4后T47D细胞中E2F1、E2F2、E2F7和E2F8 mRNA水平有不同程度的降低（均P<0.01）；与MCF-7-siNC相比，干扰B7-H4后MCF-7细胞中E2F1、E2F2、E2F3、E2F7和E2F8 mRNA水平均有不同程度的降低（P<0.05或P<0.01）。结论：干扰乳腺癌细胞B7-H4表达可下调cyclin D1和E2F家族相关转录因子的表达，导致细胞周期阻滞并抑制细胞增殖。

Objective : To investigate the changes of intestinal flora in patients with rheumatoid arthritis (RA) before and after treatment with technetium[ 99 Tc] methylenediphosphonate injection ( 99 Tc⁃MDP) . Methods : Thirty⁃two patients with RA were collected the fresh fecal specimens before and after they treated with 99 Tc⁃MDP. The genome DNA of fecal specimens was extracted and the V3 ⁃V4 regions of 16S rRNA were sequenced by Illumina Miseq platform. The sequencing results were analyzed by bioinformatics methodology. Results : The Chao , observed species , Shannon and Simpson index between the two groups in Alpha diversity analysis had no statistical difference (P > 0. 05 ) , but the value in post⁃treatment group were increased compared with the pre⁃treatment group. Compared with the pre⁃treatment of RA , there was no statistical difference in the higher proportion relative abundance on Phylum level of the intestinal microbes of RA patients , and the relative abundance of Tenericutes decreased ( P < 0. 05 ) . At the genus level , the relative abundance of Ruminococcaceae , Butyricicoccus , Christensenellaceae_R ⁃7_group , Holdemania decreased after treatment ( P < 0. 05 ) . And the relative abundances of Pasteurella , Lachnoanaerobaculum and Stomatobaculum increased (P < 0. 05) . Conclusion The abundance and species of gut microbiota in RA patients have some changes after treatment with 99Tc⁃MDP , and the diversity increases after treatment.

Objective:To study the effects of L-T4 gel combined with metformin on Ach and MCT8 content in hippocampus of hypothyroidism model rats.Methods:40 rats were randomly divided into 5 groups, normal control group (CON group) , hypothyroidism group (Hypo group) , L-T4 replacement group (L-T4 group) , metformin treatment group (MET group) and combined treatment group (L-T4+MET group) by random number table. Rats in CON group were given normal drinking water, and rats in the other four groups were given drinking water containing 0.05% propylthiouracil for 6-week hypothyroidosis modeling. At the 5th week of modeling, rats in MET group were given 1ml/100g metformin solution by intragastric administration, and rats in L-T4 group were applied with L-T4 gel agent at a dose of 0.1g/100g. L-t4+MET group were treated with L-T4 gel and metformin solution. At the end of 6-week modeling, the blood of abdominal aorta was collected, and the hippocampal tissue of the brain was quickly separated on an ice platform. Meanwhile, the trachea and thyroid were cut out and photographed to record their size. They were stored in a -80℃ refrigerator or soaked in 4% paraformaldehyde for fixation and used for immunohistochemical staining. T-test was used to confirm the difference between the data of each group, one-way analysis of variance was used to compare the means between multiple groups, and chi-square test was used when the count data were expressed as percentage ( χ2) . P<0.05 was used to indicate statistical significance between the data, and the difference was statistically significant. Results:Nishner staining showed that the optical density of the Hypo group was lower than that of the CON group ( t=8.944, P<0.001) , the optical density of the MET group was higher than that of the Hypo group ( t=4.472, P<0.001) , and the optical density of the L-T4 group was higher than that of the Hypo group ( t=4.472, P<0.001) . The optical density of rats in the combined treatment group was higher than that in the Hypo group ( t=8.944, P<0.001) , and recovered to the level of the CON group ( P=1.000) . After 2 weeks of treatment, the total thyroxine level (TT4) of the Hypo group was lower than that of the CON group ( t=14.536, P<0.001) , and the TT4 level of the MET group was higher than that of the Hypo group ( t=6.924, P<0.001) . TT4 level of L-T4 group was higher than that of Hypo group ( t=4.892, P<0.001) , TT4 level of combined treatment group was higher than that of Hypo group ( t=12.890, P<0.05) , and recovered to the level of CON group ( t=0.494, P=0.709) . After the study, the thyroid tissue of each group was collected. The thyroid tissue weight of the Hypo group was higher than that of the CON group ( t=7.906, P<0.001) , the thyroid tissue weight of the MET group and L-T4 group was lower than that of the Hypo group (MET: t=2.000, P<0.001; L-T4: t=3.000, P<0.001) , but higher than that of the CON group (MET: t=3.000, P<0.001; L-T4: t=2.000, P<0.001) . The thyroid weight of L-T4+MET group was similar to that of CON group ( P=1.000) . HE staining showed that the size of thyroid follicles was different in the combined treatment group, and the number of glial and absorbed vacuoles basically recovered similar to that of CON. After treatment, the Ach level in the Hypo group was lower than that in the CON group ( t=3.618, P<0.001) , the Ach level in the MET group was higher than that in the Hypo group ( t=3.121, P=0.016) , the Ach level in the L-T4 group was higher than that in the Hypo group ( t=3.321, P=0.027) , and the Ach level in the combined treatment group was higher than that in the Hypo group ( t=3.202, P=0.001) . And recovered to the level of CON group ( t=3.362, P=0.605) . After treatment, the MCT8 level in the Hypo group was higher than that in the CON group ( t=11.254, P<0.001) , the MCT8 level in the MET group was lower than that in the Hypo group ( t=5.679, P<0.001) , and the MCT8 level in the L-T4 group was lower than that in the Hypo group ( t=5.813, P<0.001) . The MCT8 level of the combined treatment group was lower than that of the Hypo group ( t=8.624, P<0.001) , and recovered to the level of the CON group ( t=0.587, P=0.477) . Conclusion:L-T4 gel combined with metformin has a good therapeutic effect on hypothyroidism, which can increase the level of Ach and decrease the level of MCT8 in hippocampus.