Objective To analyze the composition characteristics and biological functions of tumor cell subpopulations in glioblastoma(GBM)through multi-transcriptomics sequencing technology,and explore the hypoxia characteristics and spatial localization features of the mesenchymal-like(MES-like)tumor cell subpopulation in GBM and the influence on malignant biological behaviors.Methods Multi-transcriptomics sequencing data,including single-cell RNA sequencing(scRNA-seq)data(18 patients),bulk RNA sequencing(bulk RNA-seq)and spatial transcriptomics(ST)data of GBM,were employed to define cell subpopulations in GBM,and Gene Ontology(GO)and Gene Set Enrichment Analysis(GSEA)were utilized to analyze their functions.The proportions and locations of cell subpopulations in bulk RNA-seq data were evaluated with BayesPrism deconvolution.Immunofluorescence assay was conducted for verification on 12 paraffin samples of GBM from patients who visited the neurosurgical department of our hospital from 2015 to 2023 and met the pathological diagnostic criteria for GBM(10 males and 2 females,at an average age of 53.50 years and a median age of 54.50 years).pySCENIC was applied to predict specific transcription factors of tumor cell subpopulations.Results Tumor cells in GBM were highly heterogeneous,and could be mainly divided into 4 subpopulations:astrocyte-like(AC-like),neural progenitor-like(NPC-like),oligodendrocyte progenitor-like(OPC-like)and MES-like.Differential gene analysis found that the MES-like tumor cells highly expressed vascular endothelial growth factor A(VEGFA),adrenomedullin(ADM),N-myc downstream regulated 1(NDRG1),insulin like growth factor binding protein 5(IGFBP5),and A-kinase anchoring protein 12(AKAP12)(P<0.001).pySCENIC transcription factor prediction found that the high-active transcription factors of the MES-like tumor cells were AT-rich interaction domain 3A(ARID3A),FOS like 2,AP-1 transcription factor subunit(FOSL2),endothelial PAS domain protein 1(EPAS1),CCAAT enhancer binding protein delta(CEBPD),and CCAAT enhancer binding protein beta(CEBPB)(P<0.05).GO and GSEA enrichment analyses found that the MES-like tumor cells were enriched in hypoxia-related pathways,especially the pathway of cell responses to hypoxia levels(NES=2.437,P<0.001).BayesPrism deconvolution showed that the MES-like tumor cells mainly existed in PAN(Pseudopalisading cells around necrosis)and perinecrotic zone.Immunofluorescence assay confirmed CD44+(CD44 antigen)MES-like tumor cells were mainly located in hypoxia areas with highly expression of hypoxia inducible factor 1 subunit alpha(HIF1α)(P<0.01).Multivariate Cox regression analysis indicated that the MES-like tumor cells were significantly correlated with the adverse prognosis of GBM patients(HR=1.71,95%CI:1.38～2.11,P<0.001).Conclusion Tumor cells in GBM are of highly heterogeneity.They could be mainly divided into 4 subpopulations:AC-like,NPC-like,OPC-like and MES-like.MES-like tumor cells,mainly locating in PAN and perinecrotic zone,are characterized by hypoxia,which can promote the malignant progression of GBM.

Objective To explore the abnormality of top-down and bottom-up attention patterns in patients suffering from coronary heart disease(CHD)patients with heart-qi deficiency syndrome based on the theory of"five spirits".Methods From July 2024 to December 2024,30 CHD patients with heart-qi deficiency syndrome were recruited,and 30 subjects without CHD as the control group according to the principle of matching age,sex and years of education.Two groups of subjects were tested with top-down and bottom-up spatial cueing paradigm.Results Compared with the control group,CHD patients with heart-qi deficiency syndrome had longer valid reaction time(vRT)and lower average reaction time difference value(△RT)in top-down test(P＜0.05),and longer vSRT in bottom-up test.Correlation analysis showed that heart-qi deficiency syndrome score was positively correlated with top-down test indexes invalid reaction time(ivRT)(P＜0.05),negatively correlated with △RT(P＜0.01)and valid accurany(vAC)(P＜0.05).It was positively correlated with valid long reaction time(vLRT)(P＜0.01)and invalid long reaction time(ivLRT)(P＜0.01).Generalized linear model analysis showed that non-CHD subjects had shorter vRT(P＜0.01)and larger △ RT(P＜0.05)than CHD patients for top-down test.For bottom-up tests,non-CHD subjects had shorter vSRT than CHD patients(P＜0.05).Conclusion The change of top-down and bottom-up attention patterns in CHD patients with heart-qi deficiency syndrome provides a modern neuropsychological basis for the theory of"heart stores spirits".

Objective To evaluate the efficacy and safety of Qingre Jiedu recipe in the treatment of bipolar depression.Methods A randomized,double-blind,Chinese medicine and western medicine placebo control design was used in this study.Totally 80 subjects with bipolar depression and fiery internal depression that met the enrollment criteria,were divided into the experimental group(EG,40 cases of western medicine simulation tablets+Chinese medicine formula granules)and the control group(CG,40 cases of western medicine+Chinese medicine placebo)according to a 1∶1 ratio at last,7 cases dropped out after enrollment,EG 36 cases,CG 37 cases.TCM Heat Internal Depression Syndrome(TCMHIDS),Hamilton Depression Scale-24 Item(HAMD-24),Hamilton Anxiety Scale(HAMA),Hypomania Checklist-33(HCL-33),Young Manic Rating Scale(YMRS)and Treatment Emergent Symptom Scale(TESS)scores were assessed at baseline and at the 2nd,4th and 8th week after treatment.Important signs and adverse events were recorded.Blood routine,hepatic and renal function,urine routine and electrocardiogram were performed during the screening period and the 8th week after treatment.For the patients who dropped out of the examination program,the examination item are identical to those at week 8.The primary outcome measure was the change in HAMD score from baseline to 8th week.Secondary outcome evaluation indicators included the changes of TCMHIDS,HAMA,HCL-33 and YMRS scores from baseline to 8th week.Results The scores of the HAMD-24 between EG and CG decreased significantly compared with the baseline at different time-point,and the difference was statistically significant(P＜0.01).However,the scores of the EG on the HAMD-24 decreased more significantly compared with the CG at the 4th and 8th week,and this difference was statistically significant(P＜0.01).The TCMHIDS and HAMD scores between two groups decreased compared with the baseline at different time-point,and this difference was statistically significant(P＜0.01).However,the TCMHIDS and HAMD scores of the EG decreased more significantly ot the 4th and 8th week,compared with the CG,and this difference was statistically significant(P＜0.01).Both YMRS and HCL-33 scores decreased more significantly between two groups at different time-point,compared with the baseline,and this differences was statistically significant,but there was no difference between two groups.Conclusion TCM Qingre Jiedu recipe could effectively relieve depression and anxiety mood of bipolar depression,with more advantages than western medicine.In addition,it showed a certain effect on hypomania or manic-related symptoms of bipolar disorder,No risk of turning to hypomania or manic,better safety and less adverse reactions were observed.

Objective To explore the abnormality of top-down and bottom-up attention patterns in patients suffering from coronary heart disease(CHD)patients with heart-qi deficiency syndrome based on the theory of"five spirits".Methods From July 2024 to December 2024,30 CHD patients with heart-qi deficiency syndrome were recruited,and 30 subjects without CHD as the control group according to the principle of matching age,sex and years of education.Two groups of subjects were tested with top-down and bottom-up spatial cueing paradigm.Results Compared with the control group,CHD patients with heart-qi deficiency syndrome had longer valid reaction time(vRT)and lower average reaction time difference value(△RT)in top-down test(P＜0.05),and longer vSRT in bottom-up test.Correlation analysis showed that heart-qi deficiency syndrome score was positively correlated with top-down test indexes invalid reaction time(ivRT)(P＜0.05),negatively correlated with △RT(P＜0.01)and valid accurany(vAC)(P＜0.05).It was positively correlated with valid long reaction time(vLRT)(P＜0.01)and invalid long reaction time(ivLRT)(P＜0.01).Generalized linear model analysis showed that non-CHD subjects had shorter vRT(P＜0.01)and larger △ RT(P＜0.05)than CHD patients for top-down test.For bottom-up tests,non-CHD subjects had shorter vSRT than CHD patients(P＜0.05).Conclusion The change of top-down and bottom-up attention patterns in CHD patients with heart-qi deficiency syndrome provides a modern neuropsychological basis for the theory of"heart stores spirits".

Objective To evaluate the efficacy and safety of Qingre Jiedu recipe in the treatment of bipolar depression.Methods A randomized,double-blind,Chinese medicine and western medicine placebo control design was used in this study.Totally 80 subjects with bipolar depression and fiery internal depression that met the enrollment criteria,were divided into the experimental group(EG,40 cases of western medicine simulation tablets+Chinese medicine formula granules)and the control group(CG,40 cases of western medicine+Chinese medicine placebo)according to a 1∶1 ratio at last,7 cases dropped out after enrollment,EG 36 cases,CG 37 cases.TCM Heat Internal Depression Syndrome(TCMHIDS),Hamilton Depression Scale-24 Item(HAMD-24),Hamilton Anxiety Scale(HAMA),Hypomania Checklist-33(HCL-33),Young Manic Rating Scale(YMRS)and Treatment Emergent Symptom Scale(TESS)scores were assessed at baseline and at the 2nd,4th and 8th week after treatment.Important signs and adverse events were recorded.Blood routine,hepatic and renal function,urine routine and electrocardiogram were performed during the screening period and the 8th week after treatment.For the patients who dropped out of the examination program,the examination item are identical to those at week 8.The primary outcome measure was the change in HAMD score from baseline to 8th week.Secondary outcome evaluation indicators included the changes of TCMHIDS,HAMA,HCL-33 and YMRS scores from baseline to 8th week.Results The scores of the HAMD-24 between EG and CG decreased significantly compared with the baseline at different time-point,and the difference was statistically significant(P＜0.01).However,the scores of the EG on the HAMD-24 decreased more significantly compared with the CG at the 4th and 8th week,and this difference was statistically significant(P＜0.01).The TCMHIDS and HAMD scores between two groups decreased compared with the baseline at different time-point,and this difference was statistically significant(P＜0.01).However,the TCMHIDS and HAMD scores of the EG decreased more significantly ot the 4th and 8th week,compared with the CG,and this difference was statistically significant(P＜0.01).Both YMRS and HCL-33 scores decreased more significantly between two groups at different time-point,compared with the baseline,and this differences was statistically significant,but there was no difference between two groups.Conclusion TCM Qingre Jiedu recipe could effectively relieve depression and anxiety mood of bipolar depression,with more advantages than western medicine.In addition,it showed a certain effect on hypomania or manic-related symptoms of bipolar disorder,No risk of turning to hypomania or manic,better safety and less adverse reactions were observed.

Objective The aim of this study was to explore the role and mechanism of ferroptosis in SiO2-induced cardiac injury using a mouse model. Methods Male C57BL/6 mice were intratracheally instilled with SiO2 to create a silicosis model.Ferrostatin-1(Fer-1)and deferoxamine(DFO)were used to suppress ferroptosis.Serum biomarkers,oxidative stress markers,histopathology,iron content,and the expression of ferroptosis-related proteins were assessed. Results SiO2 altered serum cardiac injury biomarkers,oxidative stress,iron accumulation,and ferroptosis markers in myocardial tissue.Fer-1 and DFO reduced lipid peroxidation and iron overload,and alleviated SiO2-induced mitochondrial damage and myocardial injury.SiO2 inhibited Nuclear factor erythroid 2-related factor 2(Nrf2)and its downstream antioxidant genes,while Fer-1 more potently reactivated Nrf2 compared to DFO. Conclusion Iron overload-induced ferroptosis contributes to SiO2-induced cardiac injury.Targeting ferroptosis by reducing iron accumulation or inhibiting lipid peroxidation protects against SiO2 cardiotoxicity,potentially via modulation of the Nrf2 pathway.

Objective:To investigate the clinical efficacy of different surgical approaches for repairing eyelid coloboma.Methods:Patients with the divided nevus of eyelid treated at Hypospadias Plastic Surgery Center, Plastic Surgery Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, from January 2005 to January 2022 were included. The surgeries were categorized into 4 types. (1) Direct excision and suture. (2) Local skin grafts: covering the defect with split- or full-thickness skin grafts according to the size of the defect on the upper and lower eyelids. (3) Combined skin grafts with orbicularis oculi myocutaneous flap: grafting skin flaps for defects on the upper eyelid and near the lower eyelid, and temporal area skin flaps based on the same side orbicularis oculi muscle pedicle for lower eyelid defects. (4) Temporal area expanded flap based on the orbicularis oculi muscle combined with skin grafts: the surgery was divided into two stages, the first stage involves the placement of an expander in the temporal area of the affected side, and the second stage involves the removal of the expander, excision of eyelid lesion tissue and formation of an island-shaped skin flap with the orbital part of the orbicularis oculi muscle pedicle as the pedicle, which was rotated 180° to cover the lower eyelid defect. Defects near the upper and lower eyelid margins were still covered with skin grafts. Follow-up was conducted through outpatient visits, telephone calls, and WeChat messaging to assess facial appearance postoperatively. SPSS 22.0 statistical software was used for analysis, and the measurement data were expressed as Mean±SD, the count data were expressed as percentage, and the comparison of preoperative and postoperative was calculated by aesthetic and functional status of facial soft-tissue deformities (A&F scores) within the group was performed by paired t-test, the difference was considered statistically significant at P<0.05. Results:A total of 34 patients were included; average age was 17.7±15.3 years. The size of the lesions varied from the smallest nevus measuring 0.3 cm × 0.2 cm and the largest measuring 14.0 cm × 14.0 cm. Direct excision with suturing was performed in 6 cases, among which 2 cases received simultaneous double eyelid surgery, the postoperative A&F score (4.54 ± 1.32) was higher than the preoperative (3.28 ± 0.98) score, the difference was not statistically significant ( P>0.05). The skin graft was performed in 10 cases, the postoperative A&F score (5.13 ± 1.59) was higher than the preoperative (2.25 ± 1.59), the difference was not statistically significant ( P>0.05). The skin graft combined with using orbicularis oculi muscle skin flap was performed in 7 cases, the postoperative A&F score of our patients (5.54 ±1.46) was significantly higher than the preoperative (2.18 ±1.61 ), the difference was statistically significant ( P<0.05). The skin graft combined with the expanded temporal area flap based on the orbicularis oculi muscle was performed in 11 cases, the A&F score of our patients after repair (4.95 ±0.60) was improved compared with the preoperative (2.18±1.48) score, and the difference was not statistically significant ( P>0.05). Twenty-eight patients were followed up for 8 to 81 months while 6 cases lost due to change of contact information, among whom three developed secondary ectropion of the lower eyelid, three experienced recurrence of nevi in the incision and grafting area, two exhibited significant pigmentation in the grafting area, and one developed secondary ptosis of the upper eyelid, while the rest of the patients were satisfied with the repair results. Conclusion:Surgical excision is the only effective treatment for eyelid cleft nevi with different clinical presentations. Covering defects on the upper and lower eyelids with different tissue transplantation method can disperse the entire nevus, resulting in more stable long-term repair effects and a more natural appearance. The combination of an orbicularis muscle flap and a free skin graft provides more stable result in the plastic surgery of medium to large eyelid split nevi. Free skin grafting of the upper and lower lids near the margins, and flap grafting of the lower lids are more consistent with the physiological state of the upper and lower lids, and the combination of different tissue grafting method can make the appearance of the face more reasonable.

Objective:To investigate the clinical efficacy of different surgical approaches for repairing eyelid coloboma.Methods:Patients with the divided nevus of eyelid treated at Hypospadias Plastic Surgery Center, Plastic Surgery Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, from January 2005 to January 2022 were included. The surgeries were categorized into 4 types. (1) Direct excision and suture. (2) Local skin grafts: covering the defect with split- or full-thickness skin grafts according to the size of the defect on the upper and lower eyelids. (3) Combined skin grafts with orbicularis oculi myocutaneous flap: grafting skin flaps for defects on the upper eyelid and near the lower eyelid, and temporal area skin flaps based on the same side orbicularis oculi muscle pedicle for lower eyelid defects. (4) Temporal area expanded flap based on the orbicularis oculi muscle combined with skin grafts: the surgery was divided into two stages, the first stage involves the placement of an expander in the temporal area of the affected side, and the second stage involves the removal of the expander, excision of eyelid lesion tissue and formation of an island-shaped skin flap with the orbital part of the orbicularis oculi muscle pedicle as the pedicle, which was rotated 180° to cover the lower eyelid defect. Defects near the upper and lower eyelid margins were still covered with skin grafts. Follow-up was conducted through outpatient visits, telephone calls, and WeChat messaging to assess facial appearance postoperatively. SPSS 22.0 statistical software was used for analysis, and the measurement data were expressed as Mean±SD, the count data were expressed as percentage, and the comparison of preoperative and postoperative was calculated by aesthetic and functional status of facial soft-tissue deformities (A&F scores) within the group was performed by paired t-test, the difference was considered statistically significant at P<0.05. Results:A total of 34 patients were included; average age was 17.7±15.3 years. The size of the lesions varied from the smallest nevus measuring 0.3 cm × 0.2 cm and the largest measuring 14.0 cm × 14.0 cm. Direct excision with suturing was performed in 6 cases, among which 2 cases received simultaneous double eyelid surgery, the postoperative A&F score (4.54 ± 1.32) was higher than the preoperative (3.28 ± 0.98) score, the difference was not statistically significant ( P>0.05). The skin graft was performed in 10 cases, the postoperative A&F score (5.13 ± 1.59) was higher than the preoperative (2.25 ± 1.59), the difference was not statistically significant ( P>0.05). The skin graft combined with using orbicularis oculi muscle skin flap was performed in 7 cases, the postoperative A&F score of our patients (5.54 ±1.46) was significantly higher than the preoperative (2.18 ±1.61 ), the difference was statistically significant ( P<0.05). The skin graft combined with the expanded temporal area flap based on the orbicularis oculi muscle was performed in 11 cases, the A&F score of our patients after repair (4.95 ±0.60) was improved compared with the preoperative (2.18±1.48) score, and the difference was not statistically significant ( P>0.05). Twenty-eight patients were followed up for 8 to 81 months while 6 cases lost due to change of contact information, among whom three developed secondary ectropion of the lower eyelid, three experienced recurrence of nevi in the incision and grafting area, two exhibited significant pigmentation in the grafting area, and one developed secondary ptosis of the upper eyelid, while the rest of the patients were satisfied with the repair results. Conclusion:Surgical excision is the only effective treatment for eyelid cleft nevi with different clinical presentations. Covering defects on the upper and lower eyelids with different tissue transplantation method can disperse the entire nevus, resulting in more stable long-term repair effects and a more natural appearance. The combination of an orbicularis muscle flap and a free skin graft provides more stable result in the plastic surgery of medium to large eyelid split nevi. Free skin grafting of the upper and lower lids near the margins, and flap grafting of the lower lids are more consistent with the physiological state of the upper and lower lids, and the combination of different tissue grafting method can make the appearance of the face more reasonable.

The increasing incidence of chronic kidney disease (CKD) has become a major global public health problem. Hypertension and CKD can cause and effect each other and often coexist. Controlling blood pressure is one of the core tasks in the treatment of CKD. Over the past 10 years, many large clinical studies have provided evidence-based medical evidence for the updating and revision of hypertension management guidelines, but there remains controversies in targets of blood pressure in hypertensive patients with CKD. Personalized and evidence-based management is the key to achieve effective control of blood pressure and slow the progression of CKD. This review will summary the epidemiological status of hypertensive patients with CKD and the progress related to the targets of controlling blood pressure in CKD.

The human biorhythm is closely related to the blood pressure level and the effect of the antihypertensive treatment of hypertension. The human circadian biorhythm changes the therapeutic effect of antihypertensive drugs by affecting the pharmacokinetics and pharmacodynamics; at the same time, following the human blood pressure rhythm in the treatment of hypertension can reduce the risk of target organ damage and cardiovascular and cerebrovascular events. Therefore, in the treatment of hypertension, the administration time and drug dosage should be adjusted according to the pharmacochronology to obtain the best curative effect and minimal side effects, and reduce the occurrence of adverse reactions and complications.