BACKGROUND:Prolyl hydroxylase domain 2(PHD2)inhibitors can regulate bone metabolism and relieve osteoporosis in ovariectomized rats.cpd17 is a small molecule oral PHD2 inhibitor newly developed by China Pharmaceutical University.It is effective in the treatment of renal anemia with few side effects,but its effect on bone formation and bone resorption is still unclear. OBJECTIVE:To investigate the effects of cpd17 on mouse osteogenic precursor cells. METHODS:Osteogenic precursor cells were treated with cpd17.Alkaline phosphatase activity and extracellular matrix mineralization were measured,and the expression levels of osteogenesis-and osteoclastogenesis-related markers,as well as PHD2 and hypoxia-inducible factor 1α,were detected.After inhibition of the hypoxia-inducible factor 1α pathway using LW6(a hypoxia-inducible factor 1α pathway inhibitor),alkaline phosphatase activity and extracellular matrix mineralization were detected again,as well as the expression levels of osteogenesis-and osteoclastogenesis-related markers,PHD2 and hypoxia-inducible factor 1α. RESULTS AND CONCLUSION:cpd17 significantly enhanced alkaline phosphatase activity and extracellular matrix mineralization,up-regulated the expression of osteogenesis-related markers,down-regulated the expression of osteoclastogenesis-related markers,up-regulated the expression of hypoxia-inducible factor 1α,down-regulate the expression of PHD2.However,cpd17's effects were significantly attenuated by LW6.To conclude,the PHD2 inhibitor cpd17 promotes osteogenic differentiation and inhibits osteoclastic differentiation through activation of the hypoxia-inducible factor 1α signaling pathway.

Objective:To explore the efficacy of long intramedullary nails versus short intramedullary nails in the treatment of AO/OTA 31-A3 intertrochanteric fractures.Methods:A retrospective analysis was conducted on 60 patients with AO/OTA 31-A3 intertrochanteric femur fractures treated between March 2019 and August 2022. The patients were randomly divided into two groups (the long nail group and the short nail group). Thirty-four patients were treated with long intramedullary nails, including 16 males and 18 females, aged 68.41±17.84 years old (range 31-96 years). Twenty-six patients were treated with short intramedullary nails, including 13 males and 13 females, aged 72.23±13.97 years old (range 31-90 years). The causes of injury, fracture classification (AO/OTA classification), intraoperative blood loss, operation time, fracture healing time, imaging indexes (fracture reduction quality, postoperative neck trunk angle, and medial support), Harris score of the hip joint at the last follow-up, one-year mortality rates and complications were compared between the two groups.Results:The follow-up time was 24.26±6.67 months in the long nail group and 24.31±5.60 months in the short nail group, and the general information of the two groups were comparable. Between the long nail and short nail group, the intraoperative blood loss was 281.47±235.28 ml vs. 121.92±84.14 ml and the operation time was 110.44±24.63 min vs. 81.15±28.54 min with significant differences ( P<0.05). While the length of hospital stay was 12.35±4.81 d vs. 10.89±4.30 d, the good rate of fracture reduction was 55.9% vs. 61.53%, the fracture healing time was 120.44±16.43 d vs. 128.07±18.33 d, the presence rate of medial support was 67.6% vs. 79.4%, and the excellent rate of Harris score was 65.4% vs. 65.4% with no significant difference between the two groups ( P>0.05). One-year mortality rates was 5.3% vs. 7.1% and complications was 11.7% vs. 15.4% with no significant difference between the two groups ( P>0.05). Conclusion:Both long intramedullary nails and short intramedullary nails are effective in the treatment of AO/OTA 31-A3 intertrochanteric femur fractures. However, surgical time and intraoperative blood loss was less in the short nail group.

Objective:To investigate the clinical effect of artificial intelligence(AI)technique in delineating target volume for patients with lung cancer during radiotherapy.Methods:A total of 60 patients with lung cancer who received radiotherapy in Pingxiang People's Hospital from September 2021 to March 2023 were selected,and they were divided into control group and observation group by random envelope method,with 30 cases in each group.The control group outlined target volume as conventional method.The observation group adopted deep learning technique to conduct train,and then,UNet network model was output and was used to complete automatic delineation for the target volume of radiotherapy for patients.The near-term efficacy,planning target region volume,radiation dose of target volume,volume and dose of organ at risk(OAR),survival time and incidence of adverse reactions were compared between two groups.Results:The objective relief rate(ORR)of observation group was 70.0％(21/30)after intervention,which was higher than that[46.67％(14/30)]of control group,and the difference was statistically significant(x2=5.691,P＜0.05).The radiation doses of internal target volume(ITV)and planning target volume in observation group were lower respectively than those in control group(t=4.591,4.934,P＜0.05),and the differences of them were significant,respectively.The volume percentages(V20,V5)of the exposed radiation dose that were higher than 20 Gy and 5 Gy in normal lung tissue,the exposed mean lung dose(MLD)of bilateral lungs and the exposed dose of 1cc volume(D1cc)of bilateral lungs in observation group were all lower than those in control group,the differences were statistically significant(t=5.249,4.571,6.092,5.339,P＜0.05),respectively.There was no statistical significance in the incidence of adverse reaction between two groups(P＞0.05).Conclusion:The application of AI technique in delineating target volume of radiotherapy for lung cancer can improve ORR,which is helpful to decrease the planning target volume,D95 and conformal index,and reduce the volume and dose of OAR.It does not increase the incidence of adverse reactions.

The treatment of advanced malignant tumors usually includes chemotherapy, radiotherapy, immunotherapy and targeted therapy, etc. However, a single treatment often faces problems such as drug resistance, toxicity and side effects. Consequently, it is urgent to seek new methods. In 2015, Siwen Hu-Lieskovan proposed "oncology cocktail therapy" firstly. Cocktail therapy is the integration of three or more different methods to exert a synergistic anti-tumor effect. In recent years, many researchers have applied cocktail therapy in basic and clinical researches. For example, the combination of chemotherapy drugs, targeted drugs and immunotherapy drugs makes the advantages of drugs complementary. The combination of hyperthermia, chemotherapy and immunotherapy can improve the tumor immunosuppressive microenvironment and stimulate immunity, and then combines with anti-programmed death receptor 1 (aPD-1) drugs to produce synergistic effects. The results show that cocktail therapy can improve the efficacy and prognosis of advanced cancer patients. In this article, the role and impact of cocktail therapy were reviewed, aiming to provide reference for in-depth exploration of new combined treatments for advanced malignant tumors.

In situ and real-time monitoring of responsive drug release is critical for the assessment of pharmacodynamics in chemotherapy. In this study, a novel pH-responsive nanosystem is proposed for real-time monitoring of drug release and chemo-phototherapy by surface-enhanced Raman spectroscopy (SERS). The Fe₃O₄@Au@Ag nanoparticles (NPs) deposited graphene oxide (GO) nanocomposites with a high SERS activity and stability are synthesized and labeled with a Raman reporter 4-mercaptophenylboronic acid (4-MPBA) to form SERS probes (GO-Fe₃O₄@Au@Ag-MPBA). Furthermore, doxorubicin (DOX) is attached to SERS probes through a pH-responsive linker boronic ester (GO-Fe₃O₄@Au@Ag-MPBA-DOX), accompanying the 4-MPBA signal change in SERS. After the entry into tumor, the breakage of boronic ester in the acidic environment gives rise to the release of DOX and the recovery of 4-MPBA SERS signal. Thus, the DOX dynamic release can be monitored by the real-time changes of 4-MPBA SERS spectra. Additionally, the strong T₂ magnetic resonance (MR) signal and NIR photothermal transduction efficiency of the nanocomposites make it available for MR imaging and photothermal therapy (PTT). Altogether, this GO-Fe₃O₄@Au@Ag-MPBA-DOX can simultaneously fulfill the synergistic combination of cancer cell targeting, pH-sensitive drug release, SERS-traceable detection and MR imaging, endowing it great potential for SERS/MR imaging-guided efficient chemo-phototherapy on cancer treatment.

[This corrects the article DOI: 10.1016/j.apsb.2022.08.024.].

OBJE CTIVE To provide reference for improving rational drug use in medical institutions and strengthening individualized rational drug use monitoring. METHODS The hospital information system （HIS）was used to retrieve the patient ’s medical information and the doctor ’s medical information ；on the basis of pre-examination of prescriptions ，the chronic disease medication monitoring and visiting frequency monitoring modules were added to construct individualized rational drug use monitoring platform. Taking hypoglycemic drugs as an example ，the number of patients who were prescribed the drug ≥3 times a month in Karamay Central Hospital （hereinafter referred to as “our hospital ”）was compared before and after the operation of the individualized rational drug use monitoring platform （Jan. to Apr. 2018 regarded as before operation ，Jan. to Apr. 2019 and 2021 regarded as after operation ）. At the same time ，the number of risk prescriptions （repeatedly prescribing the same drug ≥3 times a day）and unreasonable prescriptions after the operation of the individualized rational drug use monitoring platform （Jan. to Apr. 2019 and Jan. to Apr. 2021）in our hospital were compared. RESULTS The proport ion of patients who were over prescribed Diformin tablets from Jan. to Apr. in 2021 was lower than the same period in 2018 significantly（16.65％ vs. 27.17％，P＜0.05）. From Jan. to Apr. 2019，35.3％ of the risk prescriptions in our hospital were unqualified prescriptions ；in the same period of 2021， the proportion of unqualified prescriptions in risk prescriptions in our hospital decreased to 12.82％ ，which was statistically significant compared with 2019（P＜0.05）. CONCLUSIONS Based on the actual situation of patients ，our hospital establishes the individualized rational drug use monitoring platform by using HIS to meet the actual needs of clinical drug use. The use of the platform has significantly reduced the number of patients visiting doctors many times and unreasonable prescriptions ，and promotes rational drug use. At the same time ，the platform also further strengthens the prescription review system of our hospital and improves the level of pharmaceutical care.

Nail diseases have similar clinical manifestations with a variety of causes. Dermoscopy, a non-invasive examination tool, can be used to rapidly and comprehensively evaluate changes of diseased nails at the early stage by observing nail cuticles, nail folds, nail plates, etc. It can be applied for diagnosis and treatment of nail diseases or evaluation of surgical performance. To improve clinicians′ understanding of nail diseases, the authors summarize dermoscopic manifestations of common nail diseases based on dermoscopic manifestations of definitely diagnosed nail diseases in Department of Dermatology, Xiangya Hospital, Central South University from June 2017 to February 2019.

Overexpression of exogenous lineage-determining factors succeeds in directly reprogramming fibroblasts to various cell types. Several studies have reported reprogramming of fibroblasts into induced cardiac progenitor cells (iCPCs). CRISPR/Cas9-mediated gene activation is a potential approach for cellular reprogramming due to its high precision and multiplexing capacity. Here we show lineage reprogramming to iCPCs through a dead Cas9 (dCas9)-based transcription activation system. Targeted and robust activation of endogenous cardiac factors, including GATA4, HAND2, MEF2C and TBX5 (G, H, M and T; GHMT), can reprogram human fibroblasts toward iCPCs. The iCPCs show potentials to differentiate into cardiomyocytes, smooth muscle cells and endothelial cells . Addition of MEIS1 to GHMT induces cell cycle arrest in G2/M and facilitates cardiac reprogramming. Lineage reprogramming of human fibroblasts into iCPCs provides a promising cellular resource for disease modeling, drug discovery and individualized cardiac cell therapy.

High mobility group box 1 (HMGB1) is a nuclear protein that can bind to DNA and act as a co-factor for gene transcription. When released into extracellular fluid, it plays a proinflammatory role by acting as a damage-associated molecular pattern molecule (DAMP) (also known as an alarmin) to initiate innate immune responses by activating multiple cell surface receptors such as the receptor for advanced glycation end-products (RAGE) and toll-like receptors (TLRs), TLR2, TLR4 or TLR9. This proinflammatory role is now considered to be important in the pathogenesis of a wide range of kidney diseases whether they result from hemodynamic changes, renal tubular epithelial cell apoptosis, kidney tissue fibrosis or inflammation. This review summarizes our current understanding of the role of HMGB1 in kidney diseases and how the HMGB1-mediated signaling pathway may constitute a new strategy for the treatment of kidney diseases.