The polymerase 1 and transcript release factor (PTRF)-cytoplasmic phospholipase A2 (cPLA2) phospholipid remodeling pathway facilitates tumor proliferation in glioma. Nevertheless, blockade of this pathway leads to the excessive activation of oncogenic receptors on the plasma membrane and subsequent drug resistance. Here, CD26/dipeptidyl peptidase 4 (DPP4) was identified through screening of CRISPR/Cas9 libraries. Suppressing PTRF-cPLA2 signaling resulted in the activation of the epidermal growth factor receptor (EGFR) pathway through phosphatidylcholine and lysophosphatidylcholine remodeling, which ultimately increased DPP4 transcription. In turn, DPP4 interacted with EGFR and prevented its ubiquitination. Linagliptin, a DPP4 inhibitor, facilitated the degradation of EGFR by blocking its interaction with DPP4. When combined with the cPLA2 inhibitor AACOCF3, it exhibited synergistic effects and led to a decrease in energy metabolism in glioblastoma cells. Subsequent in vivo investigations provided further evidence of a synergistic impact of linagliptin by augmenting the sensitivity of AACOCF3 and strengthening the efficacy of temozolomide. DPP4 serves as a novel target and establishes a constructive feedback loop with EGFR. Linagliptin is a potent inhibitor that promotes EGFR degradation by blocking the DPP4-EGFR interaction. This study presents innovative approaches for treating glioma by combining linagliptin with AACOCF3 and temozolomide.

Objective: To identify the social ecological factors of individual, family, and physical environments for affecting the development of fundamental motor skills (FMS) among overweight and obese children, so as to provide a basis for the future intervention design and policy making. Methods: From March to April 2022, one public primary school was recruited from each of the 4 main urban areas in Shijiazhuang, and a total of 425 children in schools were recruited for data collection including individual, family, physical environmental factors, by using a stratified cluster random sampling approach. Test of Gross Motor Development-Third Edition (TGMD-3) was used to evaluate children s FMS. Hierarchical linear regression model was employed to analysis the associations between the 18 factors for individual, family, and physical environments, and the FMS of overweight and obese children. Results: Individual level including the child s age, gender and sleep duration, and family level including high family economic level, parental support for physical activity, and the physical activity environment surrounding the family and community were consistent predictors of movement skills ( B =0.422, -1.972, 0.014, 0.045, 1.042, 0.827, 1.898), ball skills ( B =0.858, 3.953, 0.013, 0.092, 2.141, 1.173, 1.954), and composite skills ( B =1.305, 1.915, 0.028, 0.142, 3.091, 1.962, 3.879) among overweight and obese children ( P <0.05). Furthermore, child s body mass index (BMI), moderate to vigorous physical activity, perceived motor competence, pleasure of exercise,as well as BMI and physical activity levels of their primary caregiver, were associated with different types of FMS ( P <0.05). Individual, family, and physical environmental factors had moderate to high predictive explanatory power for FMS among overweight and obese children ( 2=0.69, 0.75, 0.93, P <0.01). Conclusions The factors influencing the development of FMS in overweight and obese children are multifaceted, with individual, family, and physical environment factors all playing significant roles.Corresponding measures should be actively taken to improve FMS in overweight and obese children.

Objective To investigate the expression of pepsin in vocal cord polyps and vocal cord cancer,and to compare the difference of pepsin expression.Methods From May 2020 to December 2021,27 patients with vocal cord polyp,27 patients with vocal cord cancer and 23 healthy volunteers were selected.RSI and RFS scoring scales were used for scoring,pepsin detection kit was used for saliva pepsin detection,and immunohistochemical methods were used to detect the expression of pepsin in vocal cord tissues of patients with vocal cord polyps and vocal cord cancer.Results The RSI score,RFS score and pepsin test kit results of vocal cord polyp group and vocal cord canc-er group were higher than those of non-vocal cord disease group,and the differences of the three indexes were statis-tically significant(P＜0.05).RSI score,pepsin detection kit results and pepsin immunohistochemistry results of vocal cord polyp group showed no significant difference compared with vocal cord cancer group(P＞0.05).The RFS score of vocal cord polyp group was significantly different from that of vocal cord cancer group(P＜0.05).Conclusion Pepsin may be an important pathogenic factor of vocal cord polyp and vocal cord cancer,and play an im-portant role in the occurrence of these two diseases.The difference of pepsin expression in vocal cord polyp and vo-cal cord cancer suggests that pepsin may have different pathogenesis.

177Lu-prostate specific membrane antigen(PSMA)radio-ligand therapy has been approved abroad for advanced prostate cancer and has been in several clinical trials in China.Based on domestic clinical practice and experimental data and referred to international experience and viewpoints,the expert group forms a consensus on the clinical application of 177Lu-PSMA radio-ligand therapy in prostate cancer to guide clinical practice.

Osteoporotic proximal humeral fracture (OPHF) is one of the common osteoporotic fractures in the aged, with an incidence only lower than vertebral compression fracture, hip fracture, and distal radius fracture. OPHF, secondary to osteoporosis and characterized by poor bone quality, comminuted fracture pattern, slow healing, and severely impaired shoulder joint function, poses a big challenge to the current clinical diagnosis and treatment. In the field of diagnosis, treatment, and rehabilitation of OPHF, traditional Chinese and Western medicine have accumulated rich experience and evidence from evidence-based medicine and achieved favorable outcomes. However, there is still a lack of guidance from a relevant consensus as to how to integrate the advantages of the two medical systems and achieve the integrated diagnosis and treatment. To promote the diagnosis and treatment of OPHF with integrated traditional Chinese and Western medicine, relevant experts from Orthopedic Expert Committee of Geriatric Branch of Chinese Association of Gerontology and Geriatrics, Youth Osteoporosis Group of Orthopedic Branch of Chinese Medical Association, Osteoporosis Group of Orthopedic Surgeon Branch of Chinese Medical Doctor Association, and Osteoporosis Committee of Shanghai Association of Integrated Traditional Chinese and Western Medicine have been organized to formulate Expert consensus on the diagnosis and treatment of osteoporotic proximal humeral fracture with integrated traditional Chinese and Western medicine ( version 2024) by searching related literatures and based on the evidences from evidence-based medicine. This consensus consists of 13 recommendations about the diagnosis, treatment and rehabilitation of OPHF with integrated traditional Chinese medicine and Western medicine, aimed at standardizing, systematizing, and personalizing the diagnosis and treatment of OPHF with integrated traditional Chinse and Western medicine to improve the patients ′ function.

Objective:To establish a rapid pipeline for whole genome sequencing of Chikungunya virus (CHIKV) by combining imbricated multiplex-PCR amplification and Illumina high-throughput sequencing platform.Methods:The primary reference sequences of CHIKV were downloaded from the National Center for Biotechnology Information (NCBI) database, covering all genotypes of CHIKV. After multiple alignments using the Mafft software and phylogenetic analysis, the 20 CHIKV references were selected for primer design. The Primal Scheme tool and Geneious Prime software were used to design, evaluate and optimize the primer panel. Finally, seven CHIKV-positive samples were involved in the validation of the primer panel.Results:All the amplicons of the designed panel were generated successfully. The consensuses generated from the mapping results could cover 100.00% of the coding region of the CHIKV genome when the Ct-value of the sample was less than 33, as the percentage would decrease to 99.38% when the Ct-value reached 35. The mapping percentage could be increased by 5.70%-25.43% when using the stepwise correction mapping strategy.Conclusion:The multiplex-PCR amplification method for CHIKV whole genome sequencing is relatively simple and convenient, which only requires two tubes of PCR amplification and performs well on CHIKV-positive clinical samples with different concentration levels of virus.

Objective:To establish a rapid pipeline for whole genome sequencing of Chikungunya virus (CHIKV) by combining imbricated multiplex-PCR amplification and Illumina high-throughput sequencing platform.Methods:The primary reference sequences of CHIKV were downloaded from the National Center for Biotechnology Information (NCBI) database, covering all genotypes of CHIKV. After multiple alignments using the Mafft software and phylogenetic analysis, the 20 CHIKV references were selected for primer design. The Primal Scheme tool and Geneious Prime software were used to design, evaluate and optimize the primer panel. Finally, seven CHIKV-positive samples were involved in the validation of the primer panel.Results:All the amplicons of the designed panel were generated successfully. The consensuses generated from the mapping results could cover 100.00% of the coding region of the CHIKV genome when the Ct-value of the sample was less than 33, as the percentage would decrease to 99.38% when the Ct-value reached 35. The mapping percentage could be increased by 5.70%-25.43% when using the stepwise correction mapping strategy.Conclusion:The multiplex-PCR amplification method for CHIKV whole genome sequencing is relatively simple and convenient, which only requires two tubes of PCR amplification and performs well on CHIKV-positive clinical samples with different concentration levels of virus.

Humans ; Immune Checkpoint Inhibitors/therapeutic use* ; Prospective Studies ; HIV Infections/drug therapy* ; Anti-HIV Agents/therapeutic use* ; Comorbidity

Oral mucosal drug delivery has the advantages of rapid drug absorption, no first-pass effect and good patient compliance. However, factors such as low drug dissolution, saliva carrying the drug into the gastrointestinal tract and the existence of physiological barriers in the mucosa may affect the mucosal permeation and bioavailability of the drug. Nanotechnology applied to drug oral mucosa delivery can overcome the above disadvantages and obtain efficient absorption effect. This paper describes the physiological structure of oral mucosa and the factors affecting the absorption of drugs in oral mucosa, reviews the application of nanotechnology such as liposomes, solid lipid nanoparticles, nanostructured lipid carriers, nanoemulsions, polymer nanoparticles, polymer micelles and nanohybrid suspensions in oral mucosal drug delivery and the mechanism of promoting drug absorption, summarizes the main problems of current research, and gives an outlook on the application of nano oral mucosal drug delivery system. The main problems of current research are summarized, and the prospects for the application of nano oral mucosal drug delivery systems are discussed.