Objective To explore the mechanism of Zishen Jianpi Huayu Tablets(Corni Fructus,Notoginseng Radix et Rhizoma,Astragali Radix,Puerariae Lobatae Radix,Spatholobi Caulis,Rehmanniae Radix)in the treatment of diabetic retinopathy(DR)by means of network pharmacology and molecular docking technique,and verified by in vitro experiments.Methods The active components of Zishen Jianpi Huayu Tablets and their corresponding target proteins were screened using the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP)and the BATMAN-TCM database.Drug target proteins were converted to their corresponding gene names through the UniProt database.DR-related targets were searched using"diabetic retinopathy"as a keyword in GeneCards,DrugBank,OMIM,and TTD databases.Common targets between the disease and the drug were identified using the Venny tool.These common targets were analyzed using the String database,a protein-protein interaction(PPI)network was constructed.Topological heterogeneity analysis was performed using Cytoscape 3.9.1 to select core targets and create a PPI network diagram.These common targets were entered into the Metascape database for Gene Ontology(GO)function analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analysis to identify potential action pathways.Molecular docking of the main active components and core targets was performed using Auto Dock tools software,followed by further experimental validation.The CCK-8 assay was used to assess the effect of Zishen Jianpi Huayu Tablet medicated serum on the cell viability of Human Retinal Microvascular Endothelial Cells(HRmECs)under high glucose conditions,and RT-qPCR was used to measure the expression of IL-1β,AKT1,VEGFA,and TP53 mRNA in HRmECs.Results(1)The effective components and corresponding target proteins of Zishen Jianpi Huayu Tablets were screened by Traditional Chinese Medicine System Pharmacology Database and Analysis Platform(TCMSP)and BATMAN-TCM database.The disease-related targets of DR were searched by GeneCards,OMIM and TTD databases.The use of VENNY platform for drug active components target and DR disease-related target to take intersection(common target),that is,Zishen Jianpi Huayu Tablets in the treatment of DR potential target.The network of"drugs-active components-common targets"was constructed to screen out the key active components of Zishen Jianpi Huayu Tablets in the treatment of DR.Import the common target into STRING database,obtain the PPI network relationship,and screen out the core target.Metascape platform was used to analyze the GO function and KEGG pathway enrichment of the common targets.The key active components and core targets were verified by Autodock 4 software for molecular docking.(2)The drug-containing serum and blank serum of Zishen Jianpi Huayu Tablets was prepared.Human retinal microvascular endothelial cells(HRmECs)were randomly divided into 5 groups:the control group(low-sugar DMEM medium+10%blank serum),high-glucose group(high-sugar DMEM medium+10%blank serum)and Zishen Jianpi Huayu Tablets containing low-,medium-and high-dose serum(high-sugar DMEM medium+10%low-,medium-and high-dose drug containing serum)were detected after 48 hours of culture.The proliferative activity of HRmECs cells was detected by CCK-8 method,and the mRNA expressions of IL-1β,AKT1,VEGFA and TP53 in HRmECs cells were detected by RT-qPCR method.Conclusion Zishen Jianpi Huayu Tablets may act on core targets such as IL-1β,IL-6 and VEGFA,as well as key pathways such as NF-κB signaling pathway,AGE-RAGE signaling pathway and PI3K-AKT pathway through various active components such as quercetin,kaempferol and rehmannia flavonoids,so as to play a therapeutic role in DR.

Objective This study aims at establishing a teaching catalog and content for breast rare dis-eases and developing the syllabus for the breast rare disease using integrated multimodality of case-/problem-/resource-based learning(CBL+PBL+RBL).Methods By conducting bibliometrics co-occurrence analysis,we collected 6291 articles on breast rare disease published from January,1975 to June,2024.Additionally,we re-trieved the Textbook on Rare Diseases,the Catalog of Chinese Rare Disease,and Second Batch of Rare Dis-ease Catalog and then decided the teaching content.Results From 16,387 keywords,1000(6.1％)keywords were identified through co-occurrence analysis,including 50(0.3％)candidate diseases.These were classified into three categories:rare primary breast diseases,rare genetic mutation-related diseases associated with breast cancer,and rare systemic multi-system diseases involving the breast.From the candidate list,20(0.1％)rare primary breast diseases were further selected for their notable clinical teaching significance,and significant multi-systemic diseases affecting the breast,whether related to gene mutations or not.Teaching plans were draf-ted using a diversified parallel teaching approaches,taking into account the characteristics of different diseases and the focus of different teaching methods.Conclusions This study initiated the development of the teaching content for breast rare diseases and developed the teaching syllabus using the CBL+PBL+RBL integrated multi teaching model and targeting each rare breast disease for the critical point for teaching.

Objective:To compare the antiosteoporosis effect of conventional treatment and conventional treatment combined with Denosumab after percutaneous kyphoplasty (PKP) for osteoporotic vertebral compression fractures (OVCF).Methods:A retrospective cohort study was conducted to analyze the clinical data of 211 patients with OVCF admitted to the Second Affiliated Hospital of Soochow University from September 2020 to September 2022. All the patients were female, aged 56-90 years [(71.4±8.1)years]. The bone mineral density T-score of the lumbar spine was (-2.6±1.0)SD before operation. Fracture segments included T 1-T 9 in 45 patients, T 10-L 2 in 146, and L 3-L 5 in 69. Of all, 174 patients were treated with single-segment surgery, 25 with two-segment surgery and 12 with surgery involving three or more segments. According to the wishes of the patients, 107 patients were treated with daily oral administration of calcium and active Vitamin D after PKP (conventional treatment group) and 104 patients with Denosumab combined with the conventional treatment after PKP (Denosumab therapy group). The bone mineral density T-scores of the lumbar spine of the two groups were compared before surgery and at the last follow-up. The visual analogue scale (VAS) and Oswestry disability index (ODI) before surgery, at 3 days, 6 months after surgery, and at the last follow-up were evaluated and the refracture rate after surgery was detected. Possible adverse effects after medication during anti-osteoporosis treatment were observed in two the groups. Results:All the patients were followed up for 12-24 months [(13.5±2.0)months]. Before surgery, the bone mineral density T-score of the lumbar spine was (-2.7±1.1)SD in the Denosumab therapy group and (-2.5±0.8)SD in the conventional treatment group ( P>0.05). At the last follow-up, the bone mineral density T-score of the lumbar spine was (-2.1±1.1)SD in the Denosumab therapy group, significantly higher than (-2.5±0.9)SD in the conventional treatment group ( P<0.05). In the Denosumab therapy group, the bone mineral density T-score of the lumbar spine at the last follow-up was significantly increased compared to that before surgery ( P<0.01), while there was no significant difference in the conventional treatment group ( P<0.05). Before surgery and at 3 days after surgery, the VAS scores and ODI values were (8.5±0.9)points, (2.8±0.8)points, 48.7±4.8 and 25.6±4.0 in the Denosumab therapy group, which was not statistically different from those in the conventional treatment group [(8.5±1.3)points and (2.8±0.9)points, 47.9±7.0 and 25.9±3.7] ( P>0.05). At 6 months after surgery and at the last follow-up, the VAS scores and ODI values were (2.2±0.8)points, (1.7±0.8)points, 24.2±3.6 and 23.2±4.1 in the Denosumab therapy group, significantly lower than those of the conventional treatment group [(2.8±0.9)points, (2.8±1.1)points, 26.4±3.2 and 27.3±4.0] ( P<0.01). The VAS scores at each time point after surgery in both groups decreased significantly compared with those before surgery ( P<0.05). The VAS scores continued to decrease after surgery in the Denosumab therapy group ( P<0.05), while no significant difference was found among those at different time points in the conventional treatment group ( P>0.05). The ODI values at each time point after surgery in both groups significantly decreased compared to those before surgery ( P<0.05). The ODI values continued to decrease after surgery in the Denosumab therapy group ( P<0.05), while in the conventional treatment group, no significant difference was found between those at 6 months after surgery and those at 3 days after surgery ( P>0.05) and they were improved at the last follow-up compared with those at 3 days after surgery ( P<0.05). The refracture rate after surgery was 6.7% (7/104) in the Denosumab therapy group, significantly lower than 16.8% (18/107) in the conventional treatment group ( P<0.05). No serious complications were observed during the antiosteoporosis period in either group. Conclusion:Compared with daily oral administration of Calcium and active Vitamin D after PKP, the conventional treatment combined with Denosumab after PKP can effectively increase the bone density, relieve pain continuously, improve functional restoration, and reduce the risk of refracture in OVCF patients.

Liver fibrosis is a reversible pathological process caused by chronic liver damage and a major risk factor for hepatocellular carcinoma (HCC). Hepatic stellate cell (HSC) activation is considered the main target for liver fibrosis therapy. However, the efficiency of this strategy is limited due to the complex microenvironment of liver fibrosis, including excessive extracellular matrix (ECM) deposition and hypoxia-induced imbalanced ECM metabolism. Herein, nilotinib (NIL)-loaded hyaluronic acid (HA)-coated Ag@Pt nanotriangular nanozymes (APNH NTs) were developed to inhibit HSCs activation and remodel the microenvironment of liver fibrosis. APNH NTs efficiently eliminated intrahepatic reactive oxygen species (ROS) due to their inherent superoxide dismutase (SOD) and catalase (CAT) activities, thereby downregulating the expression of NADPH oxidase-4 (NOX-4) and inhibiting HSCs activation. Simultaneously, the oxygen produced by the APNH NTs further alleviated the hypoxic microenvironment. Importantly, the released NIL promoted collagen depletion by suppressing the expression of tissue inhibitor of metalloproteinase-1 (TIMP-1), thus synergistically remodeling the microenvironment of liver fibrosis. Notably, an in vivo study in CCl₄-induced mice revealed that APNH NTs exhibited significant antifibrogenic effects without obvious long-term toxicity. Taken together, the data from this work suggest that treatment with the synthesized APNH NTs provides an enlightening strategy for remodeling the microenvironment of liver fibrosis with boosted antifibrogenic activity.

Objective:To compare the clinical efficacy of robot-assisted percutaneous screw implantation and free-hand open screw implantation by Wiltse approach in the treatment of thoracolumbar fracture.Methods:A retrospective cohort study was performed to analyze the clinical data of 71 patients with thoracolumbar fracture admitted to Second Affiliated Hospital of Soochow University from May 2018 to May 2020. There were 52 males and 19 females, with age range of 22-54 years［(41.0±7.8)years］. Of all, 33 patients were treated with robot-assisted percutaneous screw implantation (Group A) and 38 patients were treated with free-hand open screw implantation by Wiltse approach (Group B). Following parameters were measured, including frequency of radiation exposure, operation time, intraoperative blood loss, length of hospital stay, incidence of complications, rate of fracture healing at 3 months and 6 months postoperatively, visual analogue scale (VAS) and Oswestry dysfunction index (ODI) at 3 days, 3 months, 6 months postoperatively and at the last follow-up, anterior vertebral body height ratio and sagittal Cobb angle preoperatively, at 3 days postoperatively and at the last follow-up, and rate of screw implantation of grade A and B and rate of facet joint violation at 3 days postoperatively.Results:All patients were followed up for 10-24 months［(15.2±4.4)months］. Frequency of radiation exposure and operation time showed no statistical differences between the two groups (both P>0.05). Intraoperative blood loss was 100(100, 135)ml in Group A, less than 160(120, 200)ml in Group B ( P<0.01). Length of hospital stay was 8(7, 11) days in Group A, shorter than 12(10, 16)days in Group B ( P<0.01). There were no complications such as infection, spinal nerve injury or cerebrospinal fluid leakage in both group. There were no significant differences between the two groups in the rate of fracture healing at 3 and 6 months postoperatively (all P>0.05). VAS and ODI in Group A was 3(2, 4)points and 21(18, 23)points at 3 days postoperatively, lower than 4 (3, 5)points and 27(20, 32)points in Group B ( P<0.05 or 0.01), and the two groups showed no significant differences in VAS and ODI at other time points (all P>0.05). There were no significant difference in the anterior vertebral body height ratio or sagittal Cobb angle between the two groups at 3 days postoperatively and at the last follow-up (all P>0.05). Rate of screw implantation of grade A and B was 96.5% (191/198) in Group A, higher than 90.4% (206/228) in Group B ( P<0.05). Rate of facet joint violation was 4.0%(8/198) in Group A, lower than 11.8% (27/228) in Group B ( P<0.01). Conclusion:For thoracolumbar fracture, robot-assisted percutaneous screw implantation is superior to free-hand open screw implantation by Wiltse approach in terms of less bleeding, shorter hospitalization, earlier pain alleviation, higher accuracy of screw implantation and lower risk of facet joint violation.

To determine the physicians′compliance of hour-1 bundle for sepsis. A management system of hour-1 bundle for sepsis was established. The clinical data of 286 sepsis patients were collected, who were classified into 3 months before the bundle (control group), 9 months during process (observation group) and 3 months after bundle (study group). The compliance of hour-1 bundle implementation was compared in three groups. The results showed that with the application and implementation of the management system, the compliance of hour-1 bundle for sepsis in the control group, observation group and study group was 58.3%(28/48), 69.1%(105/152) and 88.4%(76/86) respectively (χ 2=7.053, P=0.029). The 28 day mortality in sepsis patients was 41.7%(20/48), 34.9%(53/152) and 23.3%(20/86) respectively (χ 2=5.576, P=0.062).The management system of hour-1 bundle for sepsis can effectively improve the physicians′ compliance.

Objective: Due to the complicated compounds and the synergistic effect of multi-compounds, the quality control and assessment of Chinese materia medica (CMM) encounters a great challenge about how to identify the key compounds, which are directly correlated with its efficacy and safety. On the guidance of study on quality marker (Q-Marker), identification of Q-Markers was performed from Hedan Tablet (HDT) by the aid of the “spider-web” mode and hepatotoxicity evaluation derived from our previous researches and literatures. Methods: By the established ultra performance liquid chromatography with photodiode array detector (UPLC-PDA) method, online UPLC-DPPH· and offline antioxidant assay, 21 candidate compounds of HDT were systematically investigated and comprehensively evaluated by the “spider-web” mode for them properties of Q-Marker based on “content-stability-activity”. In addition, the Q-Markers related with hepatotoxicity based on our previous researches and literatures were identified. Results: Salvianolic acid B (SaB), quercetin-3-O-glucuronide (Qug), isoquercitrin (IQ) and hyperoside (Hyp) were adopted as the preferable Q-Markers of HDT according to the shaded area (A) of tested compounds in “spider-web” mode. Psoralen (Ps), isopsoralen (IP), psoralenoside (PO) and isopsoralenoside (IPO) were also strongly recommended as Q-Markers closely related with safety by considering hepatotoxicity of the accumulated Ps and IP and conversion between glycoside (PO and IPO) and aglycone (Ps and IP). Conclusion: This study provided scientific evidence for quality control and assessment of HDT, and also provided a meaningful reference for application of Q-Markers in CMM.

Objective:To detect the expression of miR-378 in cervical cancer and investigate its effects on the proliferation and invasion of cancer cells as well as the underlying mechanism.Methods:A total of 185 cervical tissue samples of women who received gynecological examination in Qilu Hospital of Shandong University from January 2012 to January 2016 were included in this study. Reverse transcription-quantitative polymerase chain reaction was performed to determine the expression of miR-378 in cervical tissue and C-33A cells. Western blot assay was performed to detect the expression of different cancer genes ATG12, CCND1 and pRb in C-33A cells. BrdU cell proliferation and Transwell invasion assay were performed to determine cell proliferation and invasion. Target Scan was used to predict and screen miR-378 gene targets and verified by a dual-luciferase reporter assay system.Results:The expression of miR-378 in cervical intraepithelial neoplasia (CIN) III lesioned tissue and cervical cancer tissue was significantly higher than that in normal cervical tissues ( F = 103.091, t = 9.381, 8.936, both P < 0.05). The expression of miR-378 in cervical cancer tissues with positive lymph node metastasis was significantly higher than that in cervical cancer tissues with negative lymph node metastasis ( t = 1.007, P < 0.01). The overexpression of miR-378 in cervical cancer tissues significantly promoted the migration and invasion of C-33A cells ( t = 5.285, P < 0.05), while low expression of miR-378 in cervical cancer tissues significantly inhibited the migration and invasion of HeLa cells ( t = 2.941, P < 0.05). The overexpression of miR-378 in C-33A cells significantly decreased the expression of ATG12, CCND1and pRb ( t = 1.382, 1.431 and 2.086, all P < 0.05). The low expression of miR-378 in C-33A cells significantly increased the expression of ATG12, CCND1 and pRb ( t = 3.961, 3.062 and 2.894, all P < 0.05). Conclusion:miR-378 can greatly promote the metastasis of cervical cancer cells. ATG12, as a direct target of miR-378, provides new insights into the molecular mechanism underlying cervical cancer pathology and therapeutic target.

Objective:To analyze the changes in biological characteristics including infectivity, growth and pathogenicity of Chlamydia muridarum ( Cm) after serial passage in vitro in special conditions in order to provide reference for screening attenuated live vaccines and virulence-related genes. Methods:Wild-type Cm strain (G0) was cultured for several passages using conventional cell culture method under alternate unassisted and assisted culture conditions. Then, the 28th generation (G28) of Cm was selected and compared with the parental G0 strain in terms of centrifugation dependence, attaching ability, intracellular growth curve, plaque size and fallopian tube lesions after genital tract infection in a mouse model. Results:Compared with the parental G0 strain, the G28 strain showed significantly decreased dependence on centrifugation during cell infection ( P<0.05) and increased attachment capacity to cells ( P<0.05). No significant differences were observed in the growth curves 32 h after cell infection or in the plaque sizes between the parental G0 and G28 strains. In the in vivo virulence test, fallopian tube lesions were observed in 87.5% of G0-infected mice and 37.5% of G28-infected mice ( P<0.05). Conclusions:Compared with the parental G0 strain, the G28 strain showed significantly enhanced in vitro infection ability, but decreased in vivo pathogenicity, which brought hope for further identification of virulence genes, isolation of attenuated strains with single genotype and development of live attenuated Chlamydia vaccines.

Diabetes mellitus is one of the most common complications after liver transplantation. The survival rate of recipients after liver transplantation with diabetes mellitus and the long-term survival rate of grafts are significantly lower than those of their counterparts without diabetes mellitus. In recent years, diabetes mellitus after liver transplantation has attracted widespread attention along with the rapid development of liver transplantation in China. Although post-transplantation diabetes mellitus (PTDM) has been extensively investigated in the past two decades, multiple problems remain to be further resolved. The study was designed to review the latest research progress upon diabetes mellitus after liver transplantation, covering the definition and diagnostic criteria of PTDM, risk factors, prevention and treatment of diabetes mellitus after liver transplantation, aiming to deepen the understanding of diabetes mellitus following liver transplantation, deliver effective prevention and management, improve the long-term survival rate and enhance the quality of life of the recipients.