Objective:To investigate the relation between temporal expression changes of proline-rich transmembrane protein 2 ( PRRT2) gene and clinical progression of PRRT2-related paroxysmal disorders (PRPDs). Methods:A retrospective analysis was performed; 19 patients with PRPDs admitted to Department of Neurology, Second Affiliated Hospital of Guangzhou Medical University from July 2021 to July 2024 were enrolled; their clinical data, including onset age and disease progression, were collected. Using Bgee database, the PRRT2 gene expressions in different age groups were analyzed to explore their relations with clinical progression. Results:Among the 19 patients, 8 were diagnosed as having infantile convulsion with choreoathetosis (ICCA), 1 patient as having infantile convulsion, and 10 as having paroxysmal kinesigenic dyskinesia (PKD). Among patients with ICCA, the disease course was divided into two stages: in infantile period, it manifested as infantile convulsions at the onset, with an onset age of (5.75±1.03) months, ranged 4-7 months; in early childhood, no seizures were noted, enjoying a silent period and lasting for a period ranged 7-15 years; subsequently, the disease relapsed during adolescent, presenting as dyskinesia, with an onset age of (11.75±3.11) years, ranged 8-16 years. Among patients with PKD, onset age was (10.40±3.17) years, ranged 5-17 years. PRRT2 expression peaked before 1 year old, declined to the lowest level at 10 years old, and then gradually increased, reaching a second peak at 17 years old; PRRT2 expression demonstrated bimodal peaks during early childhood and adolescence. Conclusion:PRPDs progression shows a certain consistency with the temporal change of PRRT2 gene expression.

Objective:To investigate the relation between temporal expression changes of proline-rich transmembrane protein 2 ( PRRT2) gene and clinical progression of PRRT2-related paroxysmal disorders (PRPDs). Methods:A retrospective analysis was performed; 19 patients with PRPDs admitted to Department of Neurology, Second Affiliated Hospital of Guangzhou Medical University from July 2021 to July 2024 were enrolled; their clinical data, including onset age and disease progression, were collected. Using Bgee database, the PRRT2 gene expressions in different age groups were analyzed to explore their relations with clinical progression. Results:Among the 19 patients, 8 were diagnosed as having infantile convulsion with choreoathetosis (ICCA), 1 patient as having infantile convulsion, and 10 as having paroxysmal kinesigenic dyskinesia (PKD). Among patients with ICCA, the disease course was divided into two stages: in infantile period, it manifested as infantile convulsions at the onset, with an onset age of (5.75±1.03) months, ranged 4-7 months; in early childhood, no seizures were noted, enjoying a silent period and lasting for a period ranged 7-15 years; subsequently, the disease relapsed during adolescent, presenting as dyskinesia, with an onset age of (11.75±3.11) years, ranged 8-16 years. Among patients with PKD, onset age was (10.40±3.17) years, ranged 5-17 years. PRRT2 expression peaked before 1 year old, declined to the lowest level at 10 years old, and then gradually increased, reaching a second peak at 17 years old; PRRT2 expression demonstrated bimodal peaks during early childhood and adolescence. Conclusion:PRPDs progression shows a certain consistency with the temporal change of PRRT2 gene expression.

Genomic studies of cancer cell alterations,such as mutations,copy number variations(CNVs),and translocations,greatly promote our understanding of the genesis and development of cancers.However,the 3D genome architecture of cancers remains less studied due to the complexity of cancer genomes and technical difficulties.To explore the 3D genome structure in clin-ical lung cancer,we performed Hi-C experiments using paired normal and tumor cells harvested from patients with lung cancer,combining with RNA sequenceing analysis.We demonstrated the feasibility of studying 3D genome of clinical lung cancer samples with a small number of cells(1×104),compared the genome architecture between clinical samples and cell lines of lung cancer,and identified conserved and changed spatial chromatin structures between normal and cancer sam-ples.We also showed that Hi-C data can be used to infer CNVs and point mutations in cancer.By integrating those different types of cancer alterations,we showed significant associations between CNVs,3D genome,and gene expression.We propose that 3D genome mediates the effects of cancer genomic alterations on gene expression through altering regulatory chromatin structures.Our study highlights the importance of analyzing 3D genomes of clinical cancer samples in addition to cancer cell lines and provides an integrative genomic analysis pipeline for future larger-scale studies in lung cancer and other cancers.

Genomic alterations are commonly found in the signaling pathways of fibroblast growth factor receptors (FGFRs). Although there is no selective FGFR inhibitors in market, several promising inhibitors have been investigated in clinical trials, and showed encouraging efficacies in patients. By designing a hybrid between the FGFR-selectivity-enhancing motif dimethoxybenzene group and our previously identified novel scaffold, we discovered a new series of potent FGFR inhibitors, with the best one showing sub-nanomolar enzymatic activity. After several round of optimization and with the solved crystal structure, detailed structure-activity relationship was elaborated. Together with metabolic stability tests and pharmacokinetic profiling, a representative compound () was selected and tested in xenograft mouse model, and the result demonstrated that inhibitor was effective against tumors with FGFR genetic alterations, exhibiting potential for further development.

The dense extracellular matrix and high interstitial fluid pressure of tumor tissues prevent the ability of anti-tumor agents to penetrate deep into the tumor parenchyma for treatment effects. C-end rule (CendR) peptides can enhance the permeability of tumor blood vessels and tumor tissues binding to neuropilin-1 (NRP-1), thus aiding in drug delivery. In this study, we selected one of the CendR peptides (sequence RGERPPR) as the parent l-peptide and substituted d-amino acids for the l-amino acids to synthesize its inverso peptide (RGERPPR). We investigated the NRP-1 binding activity and tumor-penetrating ability of (RGERPPR). We found that the binding affinity of (RGERPPR) with NRP-1 and the cellular uptake was significantly higher than that of RGERPPR. Evans Blue tests revealed that (RGERPPR) exhibited improved tumor-penetrating ability in C6, U87 and A549 tumor-bearing nude mice. Using nude mice bearing A549 xenograft tumors as a model, we found that the rate of tumor growth in the group co-administered with (RGERPPR) and gemcitabine (Gem) was significantly lower than the gemcitabine-treated group with a tumor suppression rate (TSR%) of 55.4%. Together, our results demonstrate that (RGERPPR) is a potential tumor-penetrating peptide.

Objective To evaluate the efficacy of programmed intermittent epidural bolus ( PIEB) for labor analgesia in parturients and the effect on neonates. Methods Two hundred primiparae with a sin?gleton fetus in vertex presentation, who requested labor analgesia, aged 21-36 yr, at 37 to 40 week gesta?tion, with cervical dilatation 1-3 cm, of American Society of Anesthesiologists physical statusⅠ or Ⅱ, were divided into 2 groups ( n=100 each) using a random number table: PIEB group and continuous epi?dural infusion ( CEI) group. PIEB regimens were programmed as 10 ml∕h starting from 1 h after the initial bolus. The programmed bolus dose was fixed at 5 ml with the lock?out interval set at 30 min. The drugs used in the analgesic pump were 0?08% ropivacaine and 0?4μg∕ml sufentanil in both groups. From the on?set of labor analgesia until 1 h after delivery, visual analog scale score was used to evaluate the uterine con?traction pain every hour. The modified Bromage score was used to assess the degree of motor block. The up?per spread of sensory block, total consumption of drugs, the number of attempts, duration of every stage, delivery mode, postpartum hemorrhage volume, and occurrence of adverse reactions ( dyspnea, hypoten?sion, pruritus, nausea, vomiting and urinary retention) were recorded. Apgar scores of the neonates were recorded, and the degree of primiparae′satisfaction with the analgesic efficacy was scored. Results Com?pared with group CEI, visual analog scale scores at T2?5 , the total consumption of drugs and the number of
attempts were significantly decreased, and the satisfaction score was significantly increased in group PIEB ( P<0?05) . The height of sensory block in the thoracic vertebra was significantly higher, and the height of sensory block in the lumbosacral spine was significantly lower in group PIEB than in group CEI ( P<0?05) . There were no significant differences between the two groups in the duration of every stage, delivery mode, postpartum hemorrhage volume, incidence of adverse reactions and Apgar scores of neonates (P>0?05). Conclusion PIEB provides reliable efficacy for labor analgesia in parturients, the degree of primiparae′satisfaction is high without increasing the occurrence of adverse reactions, and it exerts no effect on the neonates.

This paper introduced a new structure of MRI guided P-HIFU therapy system and software implementation based on the current P-HIFU system and interface provided by MRI vendor. The tests showed that the system's software can achieve the appropriate form of treatment need.
Magnetic Resonance Imaging ; Software Design ; Ultrasonic Therapy ; methods

Objective To study the in vitro and in vivo effects of pulsed electromagnetic fields (PEMFs) on osteoclast and osteoblast precursor cells.MethodsTo observe the in vitro effect of PEMFs,femur bone marrow cells of 8 week old female SD rats were collected.According to different treating doses,rats were divided into four treatment groups and one control group.After the treatment,the clones of granuloeyte/maerophage colony forming unit(CFU-GM) and fibroblast colony forming units(CFU-F) were measured respectively.To observe the combined in vitro and in vivo effect of PEMFs,8 week old female SD rats were randomly divided into three groups: 2-70 group,ovariectomization (OVX) group and SHAM group.Rats in the 2-70 group and OVX group were bilateral ovariectomized,while rats in the SHAM group were sham-ovariectomized.12 weeks after ovariectomization,the 2-70 group was exposed to PEMFs while the other groups were left untreated.Then,femur bone marrow cells of the rats were collected.According to the way whether the groups were treated with PEMFs,the cells were divided into six groups: 2-70 with/without treatment,OVX with/without treatment,SHAM with/without treatment.After the treatments,the clones of CFU-GM and CFU-F were measured respectively.Resultsin vitro effect of PEMFs: Compared with the control group,the CFU-GMin the treated groups reduced while the CFU-F increased.PEMFs effect in vitro and in vivo: The CFU-F in treated groupsincreased,whileno.significantdifferencesofCFU-GMwerefoundamongthegroups.Conclusion PEMFs has inhibitory effect on osteoelast precursor cells and enhances the proliferation of osteoblast precursor cells when simply applied in vitro.When PEMFs was applied in combined manner of in vitro and in vivo,it shows that PEMFs enhance the proliferation of osteoblast precursor cells but has no inhibitory effects on osteoelast precursor cells.