Pharmacotranscriptomic profiles, which capture drug-induced changes in gene expression, offer vast potential for computational drug discovery and are widely used in modern medicine. However, current computational approaches neglected the associations within gene‒gene functional networks and unrevealed the systematic relationship between drug efficacy and the reversal effect. Here, we developed a new genome-scale functional module (GSFM) transformation framework to quantitatively evaluate drug efficacy for in silico drug discovery. GSFM employs four biologically interpretable quantifiers: GSFM_Up, GSFM_Down, GSFM_ssGSEA, and GSFM_TF to comprehensively evaluate the multi-dimension activities of each functional module (FM) at gene-level, pathway-level, and transcriptional regulatory network-level. Through a data transformation strategy, GSFM effectively converts noisy and potentially unreliable gene expression data into a more dependable FM active matrix, significantly outperforming other methods in terms of both robustness and accuracy. Besides, we found a positive correlation between RS_GSFM and drug efficacy, suggesting that RS_GSFM could serve as representative measure of drug efficacy. Furthermore, we identified WYE-354, perhexiline, and NTNCB as candidate therapeutic agents for the treatment of breast-invasive carcinoma, lung adenocarcinoma, and castration-resistant prostate cancer, respectively. The results from in vitro and in vivo experiments have validated that all identified compounds exhibit potent anti-tumor effects, providing proof-of-concept for our computational approach.

Surgical operation is the main treatment of oral and maxillofacial tumors.Dysphagia is a common postoperative complication.Swal-lowing disorder can not only lead to mis-aspiration,malnutrition,aspiration pneumonia and other serious consequences,but also may cause psychological problems and social communication barriers,affecting the quality of life of the patients.At present,there is no systematic evalua-tion and rehabilitation management plan for the problem of swallowing disorder after oral and maxillofacial tumor surgery in China.Combining the characteristics of postoperative swallowing disorder in patients with oral and maxillofacial tumors,summarizing the clinical experience of ex-perts in the field of tumor and rehabilitation,reviewing and summarizing relevant literature at home and abroad,and through joint discussion and modification,a group of national experts reached this consensus including the core contents of the screening of swallowing disorders,the phased assessment of prognosis and complications,and the implementation plan of comprehensive management such as nutrition management,respiratory management,swallowing function recovery,psychology and nursing during rehabilitation treatment,in order to improve the evalua-tion and rehabilitation of swallowing disorder after oral and maxillofacial tumor surgery in clinic.

BACKGROUND:Cell derivative is cell-derived bioactive components,including decellularized extracellular matrix,exosome,apoptotic extracellular vesicle,and conditioned medium,has the effects on immune regulation,promoting angiogenesis,bone regeneration,ligament remodeling,and is capable of promoting stem cell chemotherapy,migration,proliferation,and adhesion.Its excellent characteristics make it a promising biomaterial for application and clinical translation in the field of periodontal tissue engineering. OBJECTIVE:To review the characteristics of cell derivatives(decellularized extracellular matrix,exosome,apoptotic extracellular vesicle,and conditioned medium)and its effect and the latest progress in the field of regenerative restoration of periodontal complex tissue structures. METHODS:We searched the articles on CNKI and PubMed databases with the search terms"regeneration,periodontal tissue,tissue engineering,decellularized matrix,exosome,apoptotic extracellular vesicle,condition medium"in Chinese and English,respectively.Finally,76 articles were included for analysis and discussion. RESULTS AND CONCLUSION:(1)Among those four cell derivatives,the decellularized extracellular matrix has the best mechanical properties and fibrous structure,serving as a biomimetic scaffold to provide physiochemical signals and participate in mechanical signaling in periodontal tissue engineering,providing supporting effect suitable for periodontal regeneration.Recently,the development of soluble decellularized extracellular matrix bioinks has enabled the fabrication of regenerative scaffolds for personalized periodontal defects.(2)Exosomes are the simplest cell derivatives that have immunomodulatory capacity,promoting cell migration and differentiation.As a carrier,they can be used to carry target molecules to regulate periodontal regeneration,promote ligament remodeling and bone regeneration,and are suitable for periodontal tissue engineering.(3)Apoptotic vesicles generated from apoptotic cells have a strong immunomodulatory effect and can recruit stem cells and macrophages,which determine the fate of stem cells through signal transduction and can enhance immunomodulation to promote periodontal regeneration.Engineered extracellular vesicle is considered to have the potential to initiate targeted internal immunomodulation.(4)The extraction of conditioned medium is simple and completely noninvasive,which provides essential nutrients and growth factors for tissue regeneration.These components are crucial for successful periodontal regeneration.Therefore,the conditioned medium is especially suitable for studying the interactions between cells in vitro and has an important role in high-throughput detection in the future.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

The protein kinase B(Akt)pathway can regulate the growth,proliferation,and metabolism of tumor cells and stem cells through the activation of multiple downstream target genes,thus affecting the development and treatment of a range of diseases.Thioesterase superfamily member 4(THEM4),a member of the thioesterase superfamily,is one of the Akt kinase-binding proteins.Some studies on the mechanism of cancers and other diseases have shown that THEM4 binds to Akt to regulate its phosphorylation.Initially,THEM4 was considered an endogenous inhibitor of Akt,which can inhibit the phosphorylation of Akt in diseases such as lung cancer,pancreatic cancer,and liver cancer,but subsequently,THEM4 was shown to promote the proliferation of tumor cells by positively regulating Akt activity in breast cancer and nasopharyngeal carcinoma,which contradicts previous findings.Considering these two distinct views,this review summarizes the important roles of THEM4 in the Akt pathway,focusing on THEM4 as an Akt-binding protein and its regulatory relationship with Akt phosphorylation in various diseases,especially cancer.This work provides a better understanding of the roles of THEM4 combined with Akt in the treatment of diseases.

Objective:To investigate the impact of intermittent senescent cell clearance on the proliferation and differentiation of dental pulp stem cells (DPSC) in long-term, large-scale expansion, and to explore strategies for maintaining the youthful state of DPSC in vitro. Methods:Human-derived dental pulp stem cells were isolated from healthy permanent teeth extracted for orthodontic or impeding eruption reasons, provided by the Department of Oral and Maxillofacial Surgery at West China Hospital of Stomatology, Sichuan University. Long-term, large-scale in vitro expansion of DPSC was conducted. The study compared young DPSC (passage 5) with aged DPSC (passage 25) using cellular senescence-associated β-galactosidase staining, colony formation assay, and Alizarin Red S staining for osteogenic differentiation induction. To assess the differences between the two cell populations in terms of senescence and amplification and differentiation ability. Medicine screening for the most effective senolytic was compared among 5 common senolytics [Navitoclax (ABT-263), curcumin, dasatinib, fisetin, and quercetin]. The clearance efficacy was compared using cellular senescence-associated β-galactosidase staining to reflect the changes in senescent cell ratio. The senolytic with the highest efficacy was chosen for further experiments. The passage at which the proportion of senescent cells significantly increased was identified, and the selected senolytic was administered three times at three-generation intervals from that passage to remove senescent cells. Both the control and senolytic-treated groups were estimated by fluorescence cellular senescence-associated β-galactosidase staining, real-time fluorescence quantitative PCR (RT-qPCR), colony formation assay, wound healing assay, and Alizarin Red S staining for osteogenic differentiation induction. Subcutaneous heterotopic osteogenesis was performed in nude mice and the grafts were analyzed by HE staining and alkaline phosphatase (ALP) immunohistochemical staining. Results:The proportion of senescent cells increased as the expansion extended, leading to decreased proliferation and osteogenic differentiation ability of senescent DPSC compared to young DPSC ( P<0.05). Senescent DPSC exhibited altered mRNA expression levels of senescence-related genes, including p21, p16INK4a, IL-6, and Ki67 ( P<0.001). Among the five senolytics, ABT-263 had the biggest decreases in the proportion of senescent cells. After intermittent ABT-263 treatment during expansion, the proportion of senescent cells in the senolytic-treated group [(6.72±2.34)%] was significantly lower than that in the control group [(31.82±0.57)%] ( P<0.001). RT-qPCR confirmed that compared with the control group, mRNA expressions of p21, p16 INK4a, and IL-6 in the senolytic-treated group were significantly decreased ( P<0.05), while mRNA expressions of Ki67 were significantly increased ( P<0.01). Furthermore, the cell healing ability and osteogenic differentiation ability of the senolytic-treated group were higher than those of the control group ( P<0.05). In vivo experimental results indicated that the relative new bone area [(2.36±0.48)%] after DPSC transplantation in the senolytic-treated group was greater than that in the control group [(1.00±0.46)%] ( P<0.05), and the expression of ALP was higher than that in the control group ( P<0.01). Conclusions:ABT-263 can effectively eliminate senescent cells in long-term large-scale DPSC expansion. Continuous treatment with ABT-263 during cultivation can maintain the proliferation and differentiation ability of DPSC both in vivo and in vitro.

Pulp loss is accompanied by the functional impairment of defense, sensory, and nutrition supply. The approach based on endogenous stem cells is a potential strategy for pulp regeneration. However, endogenous stem cell sources, exogenous regenerative signals, and neovascularization are major difficulties for pulp regeneration based on endogenous stem cells. Therefore, the purpose of our research is to seek an effective cytokines delivery strategy and bioactive materials to reestablish an ideal regenerative microenvironment for pulp regeneration. In in vitro study, we investigated the effects of Wnt3a, transforming growth factor-beta 1, and bone morphogenetic protein 7 (BMP7) on human dental pulp stem cells (h-DPSCs) and human umbilical vein endothelial cells. 2D and 3D culture systems based on collagen gel, matrigel, and gelatin methacryloyl were fabricated to evaluate the morphology and viability of h-DPSCs. In in vivo study, an ectopic nude mouse model and an in situ beagle dog model were established to investigate the possibility of pulp regeneration by implanting collagen gel loading BMP7. We concluded that BMP7 promoted the migration and odontogenic differentiation of h-DPSCs and vessel formation. Collagen gel maintained the cell adhesion, cell spreading, and cell viability of h-DPSCs in 2D or 3D culture. The transplantation of collagen gel loading BMP7 induced vascularized pulp-like tissue regeneration in vivo. The injectable approach based on collagen gel loading BMP7 might exert promising therapeutic application in endogenous pulp regeneration.
Animals ; Bone Morphogenetic Protein 7/pharmacology* ; Cell Differentiation ; Cells, Cultured ; Collagen/pharmacology* ; Dental Pulp ; Dogs ; Endothelial Cells ; Gelatin ; Humans ; Methacrylates ; Mice ; Regeneration ; Stem Cells

【Objective】 To compare the clinical efficacy of unilateral biportal endoscopic （UBE） and microscopic discectomy in the treatment of lumbar disc herniation （LDH） and to explore the safety and effectiveness of this operation. 【Methods】 A total of 87 LDH patients from July 2018 to July 2021 were analyzed retrospectively， including 42 cases of unilateral biportal endoscopic discectomy and 45 cases of microscopic discectomy. Analysis was based on comparison of perioperative metrics， operation time， and estimated blood loss. Clinical outcomes were evaluated using visual analogue scale （VAS）， Oswestry disability index （ODI） and modified Macnab criterion. 【Results】 All patients were followed up for 13.3±1.18 months. In UBE group， operation time （57.12±6.35） min was shorter than that in the microscope group （62.21±7.09） min and estimated blood loss （29.31±3.62） mL was smaller than that in the microscope group （51.77±8.43） mL， with a significant difference （P<0.05）. The two groups of patients had significantly lower back pain VAS score， leg pain VAS score， and ODI index than those before operation （P<0.05）. The VAS score of lower back pain at 3 days after operation and the ODI index at 1 month after operation were significantly lower in UBE group than in the microscope group （P<0.05）. At other time points， there was no significant difference in lower back pain VAS score， leg pain VAS score or ODI index （P>0.05）. Dural sac tear occurred in 2 cases in UBE group and 3 cases in the microscope group； the incidence was not statistically significant （P>0.05）. Modified MacNab criterion evaluation at the last follow-up showed that 32 cases were excellent in UBE group， 7 cases were good， and 3 cases were fair， with the excellent and good rate of 92.9% （39/42）. The microscope group was excellent in 31 cases， good in 10 cases， and fair in 4 cases， with the excellent and good rate of 91.1% （41/45）. 【Conclusion】 UBE for LDH has a satisfactory short-term clinical efficacy， with the advantages of less trauma， greater efficiency， clear vision， and large operating space. Both UBE and microscopic discectomy can achieve good clinical results in treating LDH， but the former has the advantages of less trauma， high efficiency， and quick postoperative recovery.

Objective To evaluate prospectively the side effects and tolerance of docetaxel with concurrent late-course hyperfractionated radiotherapy after breast-conserving surgery for stage T1-T2 breast cancer, and to assess the value of this treatment in shortening the treatment time and reducing the economic burden among patients. Methods A total of 20 patients with T1-T2 breast cancer were recruited after they underwent breast-conserving surgery. The acute radiation response classification, treatment completion rate, disease-free survival, hospital stays, and treatment costs were observed. Radiotherapy for all patients was started before the last single-agent docetaxel chemotherapy. Results The completion rate of treatment and the good rate of cosmetic effect reached 100%. The main adverse reactions were hematological toxicity (leukopenia) and skin reactions, which were tolerated. The median follow-up time was 30.1 months, and the follow-up rate was 100%. The average total treatment time of this hyperfractionated radiotherapy with concurrent docetaxel was four weeks, and the total hospitalization cost savings was approximately 10, 000 yuan. The 21-month disease-free survival rate was 100%. Conclusion Stage T1-T2 breast cancer can tolerate hyperfractionated radiotherapy with concurrent chemotherapy after a breast-conserving operation. The procedure results in good local control and satisfactory cosmetic effects, with high health and economic value.

Objective:To evaluate the association between thrombus composition and mechanical recanalization,operation procedure and clinical outcome.Methods:One hundred and ninety-two consecutive stroke patients with large-vessel occlusion treated by mechanical thrombectomy using a stent retriever and (or) aspiration catheter in the Affiliated Huaian No.1 People′s Hospital of Nanjing Medical University between January 2018 and January 2020 were collected. The retrieved thrombi were quantitatively analyzed for red blood cells, white blood cells, platelets, and fibrin. The patients were divided into two groups, a erythrocyte-rich group and a fibrin-rich group based on the predominant composition in the clot. The clinical prognosis, CT value of thrombus, procedure time,number of recanalization maneuvers, and degree of vascular recanalization were compared between the two groups.Results:The retrieved clot from 138 patients with acute ischemic stroke from internal carotid artery occlusion ( n=56), middle cerebral artery occlusion ( n=62), intracranial segment of vertebral artery or basilar artery occlusion( n=20) were histologically analyzed. Erythrocyte-rich clots were present in 59 cases, while fibrin-rich clots were present in 79 cases. Cardioembolic thrombi had higher proportions of fibrin/platelets [77.2%(61/79)], less erythrocytes than noncardioembolic thrombi [45.8%(27/59), χ2=8.115, P=0.004]. Patients with erythrocyte-rich thrombi had a smaller number of recanalization maneuvers [2 (1, 2) vs 3 (2, 4), Z=-7.613, P<0.001], shorter procedure time [45 (30, 60) min vs 80 (60, 90) min, Z=-6.944, P<0.001], higher thrombus CT value [42 (32, 53) vs 36 (31, 41), Z=-2.003, P=0.045], good clinical prognosis (the ratio of modified Rankin Scale score ≤2, 62.7% (37/59) vs 39.2% (31/79), χ2=7.444, P=0.006). There was no significant difference in the location of vascular occlusion between the two groups. Conclusion:For patients whose thrombotic components are mainly red blood cells, the cause of stroke may be non cardiogenic cerebral embolism, the CT value of embolus is relatively high, the embolus is easy to remove, and the clinical prognosis is relatively good.