ObjectiveTo observe the effect of Weichang'an prescription-containing serum on ferroptosis of human gastric cancer cells and explore the possible mechanism. MethodsSD rats were administrated with 18， 36， 72 g·kg^-1·d^-1 Weichang'an prescription by gavage for preparation of serum samples containing different doses of Weichang'an prescription， which were then used to treat MKN-45 cells. The cell proliferation was examined by the cell counting kit-8 （CCK-8）. In addition， inhibitors of apoptosis， necroptosis， and ferroptosis were added， and the survival of the cells treated with the serum samples was observed. The fluorescent probe dichlorodihydrofluorescein diacetate （DCF-DA） and the lipid peroxidation sensor C11-BODIPY were employed to detect the intracellular levels of reactive oxygen species （ROS） and lipid peroxidation， respectively. The levels of ferrous ion （Fe²⁺）， glutathione （GSH）， and malondialdehyde （MDA） were detected by enzyme-linked immunosorbent assay （ELISA）. Real-time PCR and Western blotting were employed to determine the expression of nuclear factor erythroid 2-related factor 2 （Nrf2）， aldo-keto reductase family 1 member B1 （AKR1B1）， glutathione peroxidase 4 （GPX4）， acyl-CoA synthetase long-chain family member 4 （ACSL4）， signal transducer and activator of transcription 3 （STAT3）， and mitogen-activated protein kinase （MAPK）. ResultsCompared with the blank group， Weichang'an prescription-containing serum decreased the viability of MKN-45 cells （P<0.05， P<0.01） in a time- and dose-dependent manner. Compared with the Weichang'an prescription group， the apoptosis inhibitor+Weichang'an prescription group and the ferroptosis inhibitor+Weichang'an prescription group showed increased cell viability （P<0.05， P<0.01）. Compared with the blank group， Weichang'an prescription elevated the levels of ROS， lipid peroxidation， and intracellular Fe²⁺ and MDA （P<0.05， P<0.01） and lowered the level of GSH （P<0.05， P<0.01） in a dose-dependent manner. Compared with the blank group， Weichang'an prescription down-regulated the mRNA and protein levels of Nrf2， AKR1B1， and GPX4 （P<0.05， P<0.01） and up-regulated the mRNA and protein levels of ACSL4 （P<0.05， P<0.01） in a dose-dependent manner. Compared with the blank group， Weichang'an prescription down-regulated the protein levels of p-STAT3 and p-ERK （P<0.05， P<0.01） in a dose-dependent manner. ConclusionThe Weichang'an prescription-containing serum can promote the ferroptosis and inhibit the proliferation of MKN-45 cells by regulating the STAT3 and MAPK pathways.

Background Pneumoconiosis is a chronic inflammatory disease that cannot be completely cured. Therefore, how to control lung inflammation and delay of the body aging is one of the keys to treating pneumoconiosis. The studies in past two decades suggested that many small molecule drugs are able to enhance cardiopulmonary function. Objective To explore the effects of homeopathic dosing and combined dosing of β-nicotinamide mononucleotide and taurine on experimental silicosis in rats. Methods Seventy-two SD specific pathogen-free rats were randomized into 4 groups (18 mice in each group): negative control group (ultrapure water, without dust), positive control group, homeopathic treatment group, co-administered treatment group. One mL of quartz dust suspension was injected into the rat trachea by disposable non-exposed tracheal injection method (50 mg·mL⁻¹) to establish a rat silicosis model. Rats were administered by gavage since the 4th day after dust exposure. The homeopathic treatment group rats received taurine solution (0.03 g·mL⁻¹) in the morning and β-nicotinamide mononucleotide (0.03 g·mL⁻¹) in the afternoon; the co-administered treatment group rats received a mixed solution (0.015 g·mL⁻¹ β-nicotinamide mononucleotide + 0.015 g·mL⁻¹ taurine) twice, in the morning and afternoon respectively. The positive and negative control groups received equivalent of ultrapure water in the morning and afternoon. All groups of rats were administered 5 d a week for a total of 6 weeks. The rats were neutralized after 6 weeks of administration. Organ coefficient, lung hydroxyproline content, whole lung dry and wet weights, whole lung free silica content, and cell count and classification in lung lavage fluid were measured and calculated, and lung histopathological changes in lung samples were observed. Results Compared with the positive control group, the whole lung wet weight, whole lung dry weight , total cell count, neutrophil rate, lung organ coefficient, lung hydroxyproline content, and whole lung free silica content were reduce in the homeopathic treatment group, and the co-administered treatment group (P＜0.05). Compared with the negative control group, the total cell count, neutrophil rate, lung organ coefficient, lung hydroxyproline content, and whole lung free silica content were elevated in the homeopathic treatment group and the co-administered treatment group, the whole lung dry weight was elevated in the co-administered treatment group, and those differences were all statistically significant (P＜0.05). The rat lung histopathological results showed that, in the positive control group, round or oval nodules were formed in the lung tissue, which were phagocytic cellular nodules, and the alveolar structures in some areas still existed. The histopathological changes in the homeopathic treatment group and the co-administered treatment group were similar to those of the positive group, but less severe. No pathological change was observed in the lung tissue of the negative control group. Conclusion Some improvement and dust removal in experimental silicosis rats by homeopathic dosing and combined dosing of β-nicotinamide mononucleotide and taurine are observed.

Intraoperative cell salvage (IOCS) has been widely applied as an important blood conservation measure in surgical operations. However, there is currently a lack of clinical practice guidelines for the implementation of IOCS in patients with malignant tumors. This report aims to provide clinicians with recommendations on the use of IOCS in patients with malignant tumors based on the review and assessment of the existed evidence. Data were derived from databases such as PubMed, Embase, the Cochrane Library and Wanfang. The guideline development team formulated recommendations based on the quality of evidence, balance of benefits and harms, patient preferences, and health economic assessments. This study constructed seven major clinical questions. The main conclusions of this guideline are as follows: 1) Compared with no perioperative allogeneic blood transfusion (NPABT), perioperative allogeneic blood transfusion (PABT) leads to a more unfavorable prognosis in cancer patients (Recommended); 2) Compared with the transfusion of allogeneic blood or no transfusion, IOCS does not lead to a more unfavorable prognosis in cancer patients (Recommended); 3) The implementation of IOCS in cancer patients is economically feasible (Recommended); 4) Leukocyte depletion filters (LDF) should be used when implementing IOCS in cancer patients (Strongly Recommended); 5) Irradiation treatment of autologous blood to be reinfused can be used when implementing IOCS in cancer patients (Recommended); 6) A careful assessment of the condition of cancer patients (meeting indications and excluding contraindications) should be conducted before implementing IOCS (Strongly Recommended); 7) Informed consent from cancer patients should be obtained when implementing IOCS, with a thorough pre-assessment of the patient's condition and the likelihood of blood loss, adherence to standardized internally audited management procedures, meeting corresponding conditions, and obtaining corresponding qualifications (Recommended). In brief, current evidence indicates that IOCS can be implemented for some malignant tumor patients who need allogeneic blood transfusion after physician full evaluation, and LDF or irradiation should be used during the implementation process.

Objective: To analyze the infection characteristics of newly reported HIV/AIDS cases in Hangzhou City, so as to provide the reference for effective AIDS intervention. Methods: Newly reported HIV/AIDS cases in Hangzhou City in 2022 were recruited. Demographic information, HIV testing status, infection routes and sexual behaviors were collected using questionnaire surveys. Blood samples were collected before antiviral treatment, and HIV-1 pol gene sequences were detected to construct molecular transmission networks. The characteristics of HIV/AIDS cases, including infection routes, time, and location were analyzed. Factors affecting infection time and location among HIV/AIDS cases were analyzed using a multivariable logistic regression model. Results: A total of 1 007 HIV/AIDS cases were reported in Hangzhou City in 2022, with 907 cases (90.07%) completing questionnaire surveys. Among them, 833 were males (91.84%), and 532 had out-of-province household registrations (58.65%). Ninety-one molecular transmission networks were established, and 276 cases were involved, with homosexual contact as the main infection route (199 cases, 72.10%). There were 311 recently infected cases (35.34%) and 569 previously infected cases (64.66%) among 880 cases whose infection time could be determined. There were 531 locally infected. cases (70.24%) and 225 imported cases (29.76%) among 756 cases whose infection location could be determined. Multivariable logistic regression analysis showed that the HIV/AIDS cases who were identified through voluntary counseling and testing (OR=1.826, 95%CI: 1.055-3.175) and sought sexual partners through homosexual dating apps (OR=2.461, 95%CI: 1.193-5.234) were more likely to be recently infected; the cases who lived in Hangzhou City for more than one year (>1 to 5 years, OR=2.853, 95%CI: 1.552-5.358; >5 years, OR=3.534, 95%CI: 1.382-9.804), sought sexual partners through entertainment venues (OR=3.449, 95%CI: 1.390-8.935), online/social apps (OR=2.416, 95%CI: 1.084-5.488) and homosexual dating apps (OR=3.734, 95%CI: 1.677-8.493) were more likely to be locally infected; student cases were more likely to be infected outside Hangzhou City (OR=0.115, 95%CI: 0.019-0.525). Conclusions The newly reported HIV/AIDS cases in Hangzhou City in 2022 were primarily infected through homosexual contact, previously and locally. Seeking sexual partners through homosexual dating apps is an important influencing factor for recent and local infections, highlighting the need for strengthening traceback investigations of related cases.

Objective: To explore the treatment plan for severe papillary defects in the aesthetic zone caused by severe periodontitis, providing a reference for clinical practice. Methods : A patient with severe periodontitis leading to severe papillary defects in the upper anterior teeth from 12 to 23 was treated using interdental tunnel technique combined with personalized connective tissue grafting for periodontal plastic surgery, and stable soft tissue augmentation was achieved. Resin restoration was conducted to modify the crown shape of the aesthetic zone teeth, reconstruct white aesthetics, guide the shaping of the gingival papillae, reduce “black triangles,” and enhance the patient’s confidence in smiling. Results : The patient’s periodontal condition and the regeneration of soft tissues in the aesthetic zone were good, and the smile aesthetics were restored. After a 3-year follow-up, the gingival morphology, color, and texture were good, and the effect was stable. The literature review indicates that for papillary defects in the aesthetic zone, analysis should be conducted based on the following aspects: whether a defect is present in periodontal hard and soft tissues, crown shape, and the distance from the most apical part of the crown contact area to the top of the alveolar crest. Based on the analysis of aesthetic defects and surgical indications, a personalized treatment plan should be designed. Conclusion For patients with obvious papillary defects in the aesthetic zone due to the reduction of periodontal support tissues caused by severe periodontitis, factors such as periodontal hard and soft tissue defects, crown shape, and the distance from the most apical part of the crown contact area to the top of the alveolar crest should be fully considered, and a personalized treatment plan should be formulated after multidisciplinary joint consultation.

Objective: To investigate the effect of targeted silencing of DNA methyltransferase 3A(DNMT3A) on collagen deposition, proliferation and migration activity of mouse lung fibroblasts(PFs). Methods: In order to ensure the proliferation and migration activity of primary fibroblasts, the lung tissues of neonatal C57 suckling mice were taken, PFs were extracted after being sheared, and the morphology was observed and identified under the microscope. PFs cells were activated by 5 ng/ml TGF-β1for 24 h after cell attachment, and DNMT3A silencing model was constructed by small interfering RNA; The experiment was divided into control group, TGF-β1group, TGF-β1+ siRNA-NC group and TGF-β1+ siRNA-DNMT3A group. The protein expressions of DNMT3A, α-smooth muscle actin(α-SMA) and Collagen Ⅰ were detected by Western blot; Real time quantitative reverse transcription polymerase chain reaction(RT-qPCR) was used to detect the mRNA expression changes ofDNMT3A,α-SMAandCollagenⅠ. The proliferation ability of PFs was detected by CCK-8 and EdU staining; the migration ability of PFs was detected by scratch test and Transwell migration test. Results: Compared with the control group, TGF-β1induced the increase of DNMT3A in the activated PFs cell group(P<0.01), the protein and mRNA levels of fibrosis and proliferation related indicators α-SMA and Collagen Ⅰ also increased(allP<0.05), and the proliferation and migration ability of PFs increased(allP<0.000 1). Compared with the siRNA-NC group, the protein expression levels of DNMT3A(P<0.000 1) and related indicators α-SMA(P<0.01) and Collagen Ⅰ(P<0.01) significantly decreased in the DNMT3A silencing group by Western blot, and the mRNA levels ofDNMT3A,α-SMAandCollagenⅠby RT-qPCR also decreased(allP<0.001), and the proliferation(P<0.01) and migration ability(P<0.05) of PFs cells decreased compared with the control group. Conclusion Silencing DNMT3A can inhibit the deposition of collagen and the proliferation of PFs. DNMT3A can promote the proliferation and migration of PFs, and then promote the activation of PFs and the development of pulmonary fibrosis. This process may be regulated by DNA methylation modification.

Acute kidney injury (AKI) is one of the most common and severe nephropathy syndromes in clinical practice and also one of the most common serious complications after organ transplantation, with high incidence and fatality. Iron is an essential trace element in the body. Ferroptosis is a form of programmed cell death induced by the accumulation of iron-mediated lipid peroxidation, and its occurrence is closely related to iron metabolism, lipid metabolism, amino acid metabolism and multiple signaling pathways. Recent studies have shown that ferroptosis plays a key role in the occurrence and development of AKI and provides therapeutic targets for AKI. This article summarizes the regulatory mechanism of ferroptosis and its role in AKI, as well as the compounds that play an important role in the prevention and treatment of AKI by inhibiting ferroptosis, providing new ideas for the future treatment and research of AKI.

The auxin/indole-3-acetic acid (Aux/IAA) gene family is an important regulator for plant growth hormone signaling, involved in plant growth, development, as well as response to environmental stresses. In the present study, we identified SmIAA7 which is potentially associated with Salvia miltiorrhiza leaf development through comparatively analyzed the transcriptome data from different pinnate leaves. SmIAA7 was successfully isolated from S. miltiorrhiza using the specific primers. Then subsequent bioinformatic analysis, prokaryotic expression and purification, subcellular localization, and induction expression analysis under auxin and abiotic stress were performed. The full-length of SmIAA7 contained an ORF of 684 bp encoding a protein of 227 amino acid with a molecular weight of 25.3 kD. Conserved domain analysis showed that SmIAA7 contains the conserved Aux_IAA domain (pfam02309). Sequence analysis and phylogenetic tree analysis results indicated SmIAA7 was phylogenetically close to IAA7 and IAA14 from other plants, suggesting SmIAA7 involved in plant growth and development as well as response to environmental stresses. The prokaryotic expression vector pET28a-SmIAA7 was constructed and SmIAA7 recombinant protein was successfully expressed in E. coli Rosetta (DE3) strain. Subcellular localization experiment demonstrated that SmIAA7 localized in the nucleus of plant cells. Real-time fluorescence quantitative PCR results showed that the expression level of SmIAA7 was upregulated in response to auxin. Drought, low temperature, and salt stress significantly increased the transcript level of SmIAA7 gene. This study lays a foundation for further elucidating the role of SmIAA7 in leaf development, signal transduction, and stress defense in S. miltiorrhiza.

Nanoparticle delivery systems have good application prospects in the field of precision therapy, but the preparation process of nanomaterial has problems such as short in vivo circulation time, easy recognition, and clearance by the immune system in the body. In recent years, biomimetic nanoparticle delivery systems mediated by natural cell membranes have become a research hotspot to address these issues. The natural membrane biomimetic nanoparticle delivery system cleverly integrates the advantages of natural biofilm "autologous" and "artificial" functional carriers by using endogenous cell membranes to modify the surface of nanocarriers, endowing them with characteristics such as tumor targeting, low immunogenicity, and long blood circulation. Currently, biomimetic nanoparticle delivery systems have been used in the treatment of malignant tumors, cardiovascular diseases, bacterial infections, and other diseases. This paper analyzes the development status and current research hotspots of natural cell membrane camouflaged biomimetic nanoparticle delivery systems mainly reviews the latest research progress of red blood cell membrane camouflaged biomimetic nanoparticle delivery systems in the field of disease treatment in recent years. It focuses on exploring the advantages, future development prospects, and limitations of biomimetic nanoparticle delivery systems based on red blood cell membrane camouflage in improving drug delivery, to provide a reference for the in-depth research and development of this system.

In order to explore the possible role and molecular mechanism of the combined action of leech and bear bile in liver and gallbladder diseases, this study first used network pharmacology methods to screen the components and targets of leech and bear bile, as well as the related target genes of liver and gallbladder diseases. The selected key genes were subjected to interaction network and GO/KEGG enrichment analysis. Then, using sodium oleate induced HepG2 cell lipid deposition model and DL-ethionine induced mouse fatty liver model, the activity of leech and bear bile alone and in combination in reducing liver fat was evaluated in vitro and in vivo, and the expression of key pathway related proteins suggested by network pharmacology was detected by Western blot. The results of network pharmacology analysis showed that the active ingredients of leech and bear bile have 295 intersecting targets with liver and gallbladder related diseases, involving more than 200 signaling pathways, including the PI3K/Akt signaling pathway and phospholipase D signaling pathway closely related to glucose and lipid metabolism. The results of in vitro validation experiments showed that both leech and bear bile, alone and in combination, can significantly inhibit the lipid deposition induced by sodium oleate in human liver cells, reduce the triacylglycerol level in cell culture supernatant, and inhibit the lipid content in liver cells. The observation results of Nile red staining confocal microscopy showed that the combination of leech and bear bile had better activity in reducing lipid deposition in liver cells compared to using them alone. In a mouse fatty liver model, the combination of leech and bear bile can better reduce elevated organ indices, blood lipids, and liver lipid levels, as well as lower the levels of serum liver injury biomarkers. The animals used in this experiment and related disposal meet the requirements of animal welfare. Before the experiment, it was reviewed and approved by IACUC, Institute of Materia Medica, Chinese Academy of Medical Sciences. The Western blot experiment results showed that the combination of leech and bear bile can significantly upregulate the expression levels of p-PI3K and p-Akt proteins, and increase the p-PI3K/PI3K and p-Akt/Akt ratios, which is consistent with the predicted results of network pharmacology. The combination of leech and bear bile has great potential for treating fatty liver disease, and activating the PI3K/Akt pathway may be one of the important mechanisms for reducing lipid deposition in liver cells.