Objective:To explore the screening value of platelet parameters from blood cell analysis for MYH9-related disorders(MYH9-RD).Methods:A cross-sectional study was conducted with 38 patients diagnosed with MYH9-RD at Shenzhen Children's Hospital from May 1, 2016, to August 31, 2024, including 24 males and 14 females; the median age was 11.5 (3.8, 35) years; categorized by gene mutation location into "head region" ( n=8 ) and "tail region" ( n=30); and by clinical manifestations into " isolated hematological manifestations" ( n=16) and "hematological manifestations with extra-hematological involvement"( n=22). The control groups included 39 cases of immune thrombocytopenia (ITP), 38 cases of acute lymphoblastic leukemia (ALL), and 40 healthy individuals. Platelet-related parameters were detected by hematology analyzer, and platelet counts and sizes were confirmed by manually counting and microscopic observation. Kruskal-Wallis test was used to compare platelet parameters between MYH9-RD and control groups. Receiver operating characteristic (ROC) curves were used to assess the diagnostic efficacy of platelet parameters for MYH9-RD. Results:In MYH9-RD patients the median value of mean platelet volume (MPV) was 13.4 (11.2, 14.7) fl, immature platelet fraction (IPF) was 52.7% (43.5%, 58.0%), platelet large cell ratio(PLCR) was 57.6 %(45.0%, 62.9%), and microscopic large platelet ratio (PLCR-M) was 30.0% (25.0%, 30.0%).And those values weresignificantly higher than in ITP, ALL, and healthy controls (all P<0.05). Patients with MYH9 gene "head region" mutations had a lower platelet count [24.5 (15.0, 47.5)×10 9/L]than those with "tail region" mutations [69.0 (49.5, 86.3) ×10 9/L]( Z=-3.493, P<0.001), but a higher IPF ( t=2.024, P=0.044).Patients with "extra-hematological involvement had a lower platelet count than those with "isolated hematological manifestations" ( t=-2.015, P=0.043). The optimal cutoff value for diagnosing MYH9-RD with IPF was 26.7%, with a sensitivity of 100% and specificity of 98.7%; the area under the curve was 0.999 (95% CI 0.995-1.000), which was superior toMPV, PLCR and PLCR-M parameters. Conclusion:IPF is superior to other platelet parameters sush as MPV,showing high diagnostic efficacy in distinguishing MYH9-RD from ITP and ALL. It can be used as a simple and effective indicator for early screening of MYH9-RD.

Objective To explore the application effect of the"ASK-T"aspiration prevention management model in reducing the risk of aspiration in elderly patients with chronic obstructive pulmonary disease(COPD)complicated by dysphagia.Methods 196 of 409 COPD patients with aspiration risk admitted to the Respiratory Disease Department of Guangdong Provincial Hospital of Chinese Medicine,Higher Education Mega Center Hospital from July 2021 to June 2024 were selected as the study object,and 102 COPD patients with aspiration risk admitted from July 2021 to December 2022 were set as the pre-improvement group.The patients in this group received the original nursing process and management mode of the department during hospitalization.94 COPD patients with aspiration risk admitted from January 2023 to June 2024 were set as the improved group,and the patients in this group were introduced into the department and implemented an innovative improvement project:"ASK-T"anti-aspiration management mode and then received nursing management.Patients in both groups were observed and followed up for 4 weeks.The risk grade of aspiration,SSA score,DHI score,aspiration pneumonia and aspiration pneumonia,nutritional status and satisfaction after intervention were compared between the two groups.Result in the improved group was significantly lower than that in the pre-improvement group(P<0.05),and the SSA score,DHI score and total DHI score of patients in the 2 groups were significantly lower than that before intervention(P<0.05).The SSA score,DHI score and DHI total score in the improved group were lower than those in the pre-improved group(P<0.05).The results of 4-week follow-up showed that the scores of NRS-2002 for nutritional risk screening in 2 groups were lower than before intervention(P<0.05),and the scores of NRS-2002 for nutritional risk screening in the improved group were significantly lower than those in the pre-improvement group(P<0.05).The comparison showed that the incidence of aspiration and aspiration pneumonia in the improved group was lower than that in the pre-improved group(P<0.05),and the satisfaction score of patients with the relevant preventive measures was higher than that in the pre-improved group(P<0.05).Conclusion The"ASK-T"aspiration preven-tion management model,when applied in the nursing of elderly patients with COPD complicated by dysphagia,can significantly reduce the risk of aspiration and the incidence of aspiration pneumonia,effectively improve patients' swallowing function and quality of life,and enhance their nutritional status.Furthermore,this model significantly improves patient satisfaction with intervention measures,providing a scientific and effective management strategy for clinical nursing of elderly patients with COPD complicated by dysphagia.It is worthy of promotion and application in clinical practice.

Objective To investigate the potential therapeutic effects,targets,and pathways of wogonoside in hypertension-induced renal injury using the Gene Expression Omnibus(GEO)database and network pharmacology,and to validate the effects of wogonoside intervention on the renal tissues of spontaneously hypertensive rats(SHR),angiotensin Ⅱ(Ang Ⅱ)-stimulated NRK-52E cell apoptosis,and the regulation of relevant pathways through in vivo and in vitro experiments.Methods GEO dataset and network pharmacology analyses were performed to investigate the key therapeutic targets of wogonoside for hypertensive nephropathy.The STRING database was used to analyze protein-protein interactions.Biological functions were annotated via Gene Ontology(GO),and the potential signaling pathways were enriched using the Kyoto Encyclopedia of Genes and Genomes(KEGG).SHR were randomly divided into groups and given low,medium,or high doses of wogonoside(0.075,0.75,and 7.5 mg/kg)via gastric gavage for 10 weeks.Morphological changes in the kidney tissue were assessed by hematoxylin-eosin(HE)staining.Serum levels of inflammatory cytokines,including tumor necrosis factor α(TNF-α),interleukin(IL)-1 β,and IL-6,were measured using ELISA.Apoptosis rates were evaluated by TUNEL staining,and Western blot was performed to determine the expression of Bax,Bcl-2,cleaved caspase-3,and caspase-3,and the expression of phosphorylated and total extracellular signal-regulated kinases(ERK)and p38 mitogen-activated protein kinase(MAPK)proteins.An in vitro model of Ang Ⅱ-stimulated NRK-52E cells was constructed and was treated with wogonoside at different concentrations(25,50,or 100 μmol/L)for 24 h.The apoptosis rates were then assessed by Annexin V staining,and Western blot was performed to validate the expression of apoptosis-related and pathway-associated proteins.Results Analysis of dataset GSE41453 revealed 11673 upregulated and 5902 downregulated genes in the renal tissues of SHR compared to the Wistar Kyoto(WKY)rats,or the WKY control group.Through the analysis of multiple databases,371 potential targets of wogonoside were identified,resulting in 98 overlapping targets.From these,45 core therapeutic targets were identified through further analysis,including TNF,CASP3,etc.GO analysis significantly enriched processes such as the negative regulation of apoptosis.KEGG pathway enrichment analysis highlighted the apoptosis pathway,IL-17 signaling pathway,and MAPK signaling pathway as being significantly enriched.Wogonoside treatment effectively mitigated pathological damage in SHR kidney tissues and significantly inhibited the expression of inflammatory cytokines,including TNF-α,IL-1 β,and IL-6(P＜0.05).It also decreased cell apoptosis rates in SHR kidney tissues and Ang Ⅱ-stimulated NRK-52E cells,downregulated the expression of Bax and cleaved caspase-3,and upregulated Bcl-2 expression(P＜0.05).Furthermore,wogonoside treatment inhibited the phosphorylation of ERK and p38 MAPK in SHR kidney tissues and Ang Ⅱ-stimulated NRK-52E cells(P＜0.05).Conclusion Wogonoside may exert its protective effects against hypertension-induced renal injury by suppressing the inflammatory response and cell apoptosis,potentially through the regulation of the MAPK signaling pathway.

Objective To investigate the potential therapeutic effects of trifolin on hypertension-induced renal injury,as well as the key targets and pathways involved.Methods The mRNA transcriptional profiles of peripheral blood clinical samples from hypertensive patients were analyzed using Gene Expression Omnibus(GEO),a high-throughput gene expression database.The network pharmacology method was employed to screen key targets of trifolin in treating hypertension-induced renal injury.Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analyses were conducted.NRK-52E cells,a rat renal proximal tubular cell line,were used to construct an angiotensin Ⅱ(Ang Ⅱ)-stimulated cell model.Flow cytometry was performed to assess cell apoptosis rates and Western blotting was performed to determine the expression levels of apoptosis-related proteins,including Bax,Bcl-2,cleaved caspase-3,and caspase-3,and the phosphorylation and total protein levels of the key MAPK pathway proteins,including ERK,p38 MAPK,and JNK.Results Analysis of the dataset GSE75360 revealed that,compared with healthy controls,3 331 genes were upregulated and 3 197 genes were downregulated in peripheral blood mononuclear cells of hypertensive patients.According to network pharmacology analysis,472 potential targets of trifolin were identified,including CASP3 and MAPK1.Protein-protein interaction network analysis showed that these targets were closely associated with apoptosis regulatory signaling pathways.GO and KEGG pathway enrichment analyses indicated that trifolin was significantly enriched in pathways associated with negative regulation of apoptosis,apoptotic signaling pathways,and the MAPK signaling pathway.The in vitro experiments confirmed that,compared with the Ang Ⅱ group,trifolin intervention inhibited apoptosis in Ang Ⅱ-stimulated NRK-52E cells,suppressed the expression of Bax and cleaved caspase-3,promoted Bcl-2 expression,and inhibited the phosphorylation of p38 MAPK,ERK,and JNK(P<0.05).Conclusion Trifolin may exert its protective effect against hypertension-induced renal injury by inhibiting Ang Ⅱ-induced NRK-52E cell apoptosis and regulating the MAPK signaling pathway,representing an important mechanism underlying its therapeutic action.

Objective To explore the application effect of the"ASK-T"aspiration prevention management model in reducing the risk of aspiration in elderly patients with chronic obstructive pulmonary disease(COPD)complicated by dysphagia.Methods 196 of 409 COPD patients with aspiration risk admitted to the Respiratory Disease Department of Guangdong Provincial Hospital of Chinese Medicine,Higher Education Mega Center Hospital from July 2021 to June 2024 were selected as the study object,and 102 COPD patients with aspiration risk admitted from July 2021 to December 2022 were set as the pre-improvement group.The patients in this group received the original nursing process and management mode of the department during hospitalization.94 COPD patients with aspiration risk admitted from January 2023 to June 2024 were set as the improved group,and the patients in this group were introduced into the department and implemented an innovative improvement project:"ASK-T"anti-aspiration management mode and then received nursing management.Patients in both groups were observed and followed up for 4 weeks.The risk grade of aspiration,SSA score,DHI score,aspiration pneumonia and aspiration pneumonia,nutritional status and satisfaction after intervention were compared between the two groups.Result in the improved group was significantly lower than that in the pre-improvement group(P<0.05),and the SSA score,DHI score and total DHI score of patients in the 2 groups were significantly lower than that before intervention(P<0.05).The SSA score,DHI score and DHI total score in the improved group were lower than those in the pre-improved group(P<0.05).The results of 4-week follow-up showed that the scores of NRS-2002 for nutritional risk screening in 2 groups were lower than before intervention(P<0.05),and the scores of NRS-2002 for nutritional risk screening in the improved group were significantly lower than those in the pre-improvement group(P<0.05).The comparison showed that the incidence of aspiration and aspiration pneumonia in the improved group was lower than that in the pre-improved group(P<0.05),and the satisfaction score of patients with the relevant preventive measures was higher than that in the pre-improved group(P<0.05).Conclusion The"ASK-T"aspiration preven-tion management model,when applied in the nursing of elderly patients with COPD complicated by dysphagia,can significantly reduce the risk of aspiration and the incidence of aspiration pneumonia,effectively improve patients' swallowing function and quality of life,and enhance their nutritional status.Furthermore,this model significantly improves patient satisfaction with intervention measures,providing a scientific and effective management strategy for clinical nursing of elderly patients with COPD complicated by dysphagia.It is worthy of promotion and application in clinical practice.

Objective:To explore the screening value of platelet parameters from blood cell analysis for MYH9-related disorders(MYH9-RD).Methods:A cross-sectional study was conducted with 38 patients diagnosed with MYH9-RD at Shenzhen Children's Hospital from May 1, 2016, to August 31, 2024, including 24 males and 14 females; the median age was 11.5 (3.8, 35) years; categorized by gene mutation location into "head region" ( n=8 ) and "tail region" ( n=30); and by clinical manifestations into " isolated hematological manifestations" ( n=16) and "hematological manifestations with extra-hematological involvement"( n=22). The control groups included 39 cases of immune thrombocytopenia (ITP), 38 cases of acute lymphoblastic leukemia (ALL), and 40 healthy individuals. Platelet-related parameters were detected by hematology analyzer, and platelet counts and sizes were confirmed by manually counting and microscopic observation. Kruskal-Wallis test was used to compare platelet parameters between MYH9-RD and control groups. Receiver operating characteristic (ROC) curves were used to assess the diagnostic efficacy of platelet parameters for MYH9-RD. Results:In MYH9-RD patients the median value of mean platelet volume (MPV) was 13.4 (11.2, 14.7) fl, immature platelet fraction (IPF) was 52.7% (43.5%, 58.0%), platelet large cell ratio(PLCR) was 57.6 %(45.0%, 62.9%), and microscopic large platelet ratio (PLCR-M) was 30.0% (25.0%, 30.0%).And those values weresignificantly higher than in ITP, ALL, and healthy controls (all P<0.05). Patients with MYH9 gene "head region" mutations had a lower platelet count [24.5 (15.0, 47.5)×10 9/L]than those with "tail region" mutations [69.0 (49.5, 86.3) ×10 9/L]( Z=-3.493, P<0.001), but a higher IPF ( t=2.024, P=0.044).Patients with "extra-hematological involvement had a lower platelet count than those with "isolated hematological manifestations" ( t=-2.015, P=0.043). The optimal cutoff value for diagnosing MYH9-RD with IPF was 26.7%, with a sensitivity of 100% and specificity of 98.7%; the area under the curve was 0.999 (95% CI 0.995-1.000), which was superior toMPV, PLCR and PLCR-M parameters. Conclusion:IPF is superior to other platelet parameters sush as MPV,showing high diagnostic efficacy in distinguishing MYH9-RD from ITP and ALL. It can be used as a simple and effective indicator for early screening of MYH9-RD.

Epigenetic pathways play a critical role in the initiation, progression, and metastasis of cancer. Over the past few decades, significant progress has been made in the development of targeted epigenetic modulators (e.g., inhibitors). However, epigenetic inhibitors have faced multiple challenges, including limited clinical efficacy, toxicities, lack of subtype selectivity, and drug resistance. As a result, the design of new epigenetic modulators (e.g., degraders) such as PROTACs, molecular glue, and hydrophobic tagging (HyT) degraders has garnered significant attention from both academia and pharmaceutical industry, and numerous epigenetic degraders have been discovered in the past decade. In this review, we aim to provide an in-depth illustration of new degrading strategies (2017-2023) targeting epigenetic proteins for cancer therapy, focusing on the rational design, pharmacodynamics, pharmacokinetics, clinical status, and crystal structure information of these degraders. Importantly, we also provide deep insights into the potential challenges and corresponding remedies of this approach to drug design and development. Overall, we hope this review will offer a better mechanistic understanding and serve as a useful guide for the development of emerging epigenetic-targeting degraders.

Objective:To investigate mechanism of phosphodiesterase 5(PDE5)inhibitor Sildenafil in treatment of pain and inflammation in chronic pelvic pain mediated by macrophage polarization.Methods:A total of 32 adult Wistar rats were divided into 4 groups:Sham group,Experimental autoimmune prostatitis(EAP)group,Sildenafil+EAP group,MET+Sildenafil+EAP group,with 8 rats in each group.EAP model was induced by subcutaneous injection of prostate antigen(PAg)and complete Fredrin adjuvant,Sham group was injected with equivalent normal saline.EAP rats were treated with Sildenafil.Metformin was injected on basis of Silde-nafil+EAP.HE staining was used to analyze pathological changes of prostate.Response rate of pelvic pain in rats was measured by von Frey fiber method.Serum cytokines IL-10 and TNF-α levels were determined by ELISA.Numbers of iNOS+and CD16/32+macrophages and CD206+and CD10+macrophages in serum were detected by flow cytometry.Results:Compared with Sham group,EAP group showed obvious focal or multifocal inflammation in ventral prostate gland tissues,pelvic pain response rate,serum inflammatory factor TNF-α level,and number of M1-type polarization characteristic iNOS+and CD16/32+cells in EAP group were significantly increased(all P<0.05),while M2-type polarization characteristics of macrophages,IL-10 level and number of CD206+and CD10+macrophages were significantly decreased(all P<0.05).Compared with EAP group,pelvic pain response rate,TNF-α level,iNOS+and CD16/32+cell number in Sildenafil+EAP group were significantly decreased(all P<0.05),while IL-10 level and CD206+and CD10+macrophage number were significantly increased(all P<0.05).Compared with Sildenafil+EAP group,pelvic pain response rate,TNF-α level,iNOS+and CD16/32+cells in MET+Sildenafil+EAP group were significantly increased(all P<0.05),while IL-10 level and number of CD206+and CD10+macrophages were significantly decreased(all P<0.05).Conclusion:Sildenafil,a PDE5 inhibitor,blocks chronic pelvic pain and inflammation by promoting polarization of M2 macrophages.

Objective:To observe the clinical efficacy of manual therapy based on the Discovery of Posture Secret (DPS) in treating adolescent idiopathic scoliosis (AIS).Methods:Thirty-six AIS patients were randomly divided into an observation group of 17 and a control group of 16. In addition to 10 minutes of side-shift training each week, the control group was given 20 minutes of sling exercise training (SET), while the observation group underwent weekly 20-minute manual therapy sessions based on DPS on the days without SET. Before and after the 4 weeks of treatment spine curvature (Cobb angle), clavicular angle (CA), angle of trunk rotation (ATR) and vertebral rotation (VR) were measured, and the Scoliosis Research Society′s patient questionnaire 22 (SRS-22) was administered.Results:After the treatment the average Cobb angle, CA, ATR and SRS-22 score of the observation group had improved significantly compared with before the treatment. The average Cobb angle, ATR and SRS-22 score of the control group were also significantly higher, but the improvements were not as great as in the observation group. There was no significant difference in VR improvement between the two groups.Conclusion:Manual therapy based on the DPS can effectively ameliorate the scoliosis and shoulder imbalance of AIS patients.

Background Non-occupational carbon monoxide (CO) poisoning is a public health problem that seriously affect people’s health and lives. Objective To describe the prevalence of non-occupational CO poisoning during 2007—2018 in Shanghai, analyze its epidemiological characteristics and potential influencing factors, and explore effective prevention and control measures. Methods Daily reported non-occupational CO poisoning cases and meteorological factors from 2007 to 2018 were collected in Shanghai, epidemiological characteristics were analyzed by descriptive epidemiology methods, and a distributed lag nonlinear model was used to assess the association between temperature and non-occupational CO poisoning. Results A total of 2264 non-occupational CO poisoning events and 3866 cases from 2007 to 2018 were reported in Shanghai, including 59 death cases. More than half of the poisoning cases were female (56.3%), and young adults accounted for more cases than any other age group (54.8%). The poisoning events mainly occurred in winter (from December to next February); however, cases reported in summer increased in recent years. The peak period of the events was from 20:00 to 24:00. Households (85.2%) and restaurants (8.0%) were the common places of non-occupational CO poisoning events, and the main cause was improper use of gas water heater (36.9%). A nonlinear curve was found between daily average temperature of current day and the occurrence of non-occupational CO poisoning. Temperature was negatively associated with the risk of non-occupational CO poisoning when the temperature was lower than 9.6 ℃, while a positive association was found during 9.7-26.0 ℃. Conclusion Winter is a high season for non-occupational CO poisoning in Shanghai, rising cases reported in summer is also worthy of attention. Supervision should be strengthened to ban sales of unqualified gas water heaters, and health education on CO poisoning prevention and control should be conducted through multiple channels, in order to reduce the incidence of CO poisoning.