Objective:To develop a network-structured clinical pathway grouping rule based on the principles and methods of China healthcare security diagnosis related groups(CHS-DRG), for references for optimizing clinical pathway management.Methods:From August to November 2024, this study constructed a network-structured clinical pathway management framework, followed the grouping principles of CHS-DRG, and developed a network-structured clinical pathway grouping rule through literature analysis and expert discussions. 54 clinical specialists from the sample hospital were organized and grouped according to the rule for the normal magnification cases(139 218 cases) of DRG medical insurance settlement in the hospital in 2023. Using a stratified random sampling method, 205 physicians from 54 clinical specialties in the hospital were selected to quantitatively evaluate the rationality, homogeneity, and clarity of the grouping results. The Likert 5-level scoring method was wsed to assign scores.Results:The network-structured clinical pathway grouping rule and nomenclature was established. A total of 341 main pathways and 35 sub-pathways covering 169 adjacent diagnosis related groups were formed. The quantitative assessment scores for rationality, homogeneity, and clarity were 4.90, 4.87 and 4.87 points, respectively.Conclusions:The network-structured clinical pathway grouping rule based on CHS-DRG had good, feasibility and standardization, and could meet the practical needs of clinical applications.

BACKGROUND:Oligodendrocyte precursor cells are seed cells for the treatment of white matter damage diseases.Establishing an efficient and stable in vitro differentiation method is an important prerequisite for clinical translational research.OBJECTIVE:To investigate the effect of fibronectin on biological characteristics such as proliferation,migration,and differentiation of oligodendrocyte precursor cells derived from human neural stem cells.METHODS:Human neural stem cells cultured in suspension were digested into single cells using Accutase.The expression of specific markers Nestin,Sox2,Vimentin,CD133,and Musashi was detected by flow cytometry.The single cells of human neural stem cells were resuspended in oligodendrocyte precursor cell medium and seeded in six-well plates coated with different concentrations of fibronectin(0,1,2.5,5,and 10 μg/mL).Accutase digestion was performed after 7 days of culture.Cells were counted by trypan staining.Fibronectin-coated group with the strongest amplification ability and the oligodendrocyte precursor cells without fibronectin-coated group were selected for further tests.The migration ability of the two groups of cells was detected by Transwell.Flow cytometry was used to detect the expression of Olig2,Sox10,and PDGFR-α.Oligodendrocyte precursor cells were induced to differentiate into oligodendrocytes for 3 weeks,and the expression of Galc in differentiated cells was detected by immunofluorescence staining.RESULTS AND CONCLUSION:(1)H uman neural stem cells grew in suspension spheres.Flow cytometry showed that human neural stem cells highly expressed Nestin,Sox2,Vimentin,CD133,and Musashi.(2)The cell bodies of oligodendrocyte precursor cells induced by human neural stem cells were round or oval,with strong refractive nature and bipolar or tertiary protrusions.Compared with the 0 μg/mL fibronectin coating group,there was a significant difference in the amplification ability of oligodendrocyte precursor cells in the 2.5,5,and 10 μg/mL fibronectin coating groups(P＜0.05).The amplification ability of oligodendrocyte precursor cells was the strongest when the fibronectin concentration was 10 μg/mL.(3)Flow cytometry results showed that the oligodendrocyte precursor cell markers 0Iig2,Sox10,and PDGFR-α were highly expressed in the 0 and 10 μg/mL fibronectin coating groups,and there was no significant difference between the two groups(P＞0.05).(4)Transwell chamber assay results showed that compared with the 0 μg/mL fibronectin-coated group,the migration ability of oligodendrocyte precursor cells in the 10 μg/mL fibronectin-coated group was increased(P＜0.01).(5)After 3 weeks of differentiation into oligodendrocytes,oligodendrocyte precursor cells showed complex morphology with multiple branches,grids or membrane sheets.Immunofluorescence staining results showed that there was no statistical difference in the Galc positive rate of oligodendrocytes between the two groups(P＞0.05).These findings indicate that when the concentration of fibronectin coated well plate is 10 μg/mL,the proliferation and migration of oligodendrocyte precursor cells are the strongest,but it does not affect the expression of oligodendrocyte precursor cells-specific markers Olig2,Sox10,and PDGFR-α and their differentiation into oligodendrocytes.

AIM:We investigated the survival,migration and differentiation abilities of human oligodendro-cyte precursor cells(hOPC)in the brains of mice with vascular dementia(VaD),the effects of hOPC on cerebral white matter,and the underlying mechanisms.METHODS:Mouse VaD model was constructed using the bilateral common ca-rotid artery stenosis method,and the mice were randomly divided into sham,VaD and hOPC groups.Eight weeks after model establishment,the mice in VaD and hOPC groups received equal volume of vehicle(PBS)and hOPC solution,re-spectively,through the corpus callosum.Survival,migration and differentiation of hOPC in the brain were observed by im-munofluorescence staining at 4 and 12 weeks after transplantation.Twelve weeks after transplantation,the effects of hOPC on mouse brain white matter were detected by immunofluorescence staining of myelin basic protein(MBP),myelin-associ-ated glycoprotein(MAG),neurofilament protein 200(NF200)and non-phosphorylated neurofilament H(using monoclo-nal antibody SMI32),and by water maze experiments.Paracrine signaling by hOPC was explored using immunofluores-cence staining for vascular endothelial growth factor(VEGF).RESULTS:The hOPC survived in the brains of VaD mice for 12 weeks,migrated to damaged white matter areas,and partially differentiated into mature oligodendrocytes(approxi-mately 64%).Twelve weeks after transplantation,hOPC significantly increased the fluorescence intensity of MBP,MAG,and NF200(P<0.05 or P<0.01)and decreased the fluorescence intensity of SMI32(P<0.01).The VEGF expression in hOPC-treated mice was significantly higher than that in sham and VaD groups(P<0.01).The difference in water maze test performance between hOPC and sham groups was not statistically significant(P>0.05).The mice in hOPC group had a shorter latency than those in VaD group(P<0.05 or P<0.01),and performed more platform crossings than those in VaD group(P<0.05).CONCLUSION:The hOPC can survive,migrate and differentiate in the brains of VaD mice,attenuate cerebral white matter lesions,and improve cognitive function.These improvements may be attributed to cell replacement and paracrine effects.

AIM:We investigated the survival,migration and differentiation abilities of human oligodendro-cyte precursor cells(hOPC)in the brains of mice with vascular dementia(VaD),the effects of hOPC on cerebral white matter,and the underlying mechanisms.METHODS:Mouse VaD model was constructed using the bilateral common ca-rotid artery stenosis method,and the mice were randomly divided into sham,VaD and hOPC groups.Eight weeks after model establishment,the mice in VaD and hOPC groups received equal volume of vehicle(PBS)and hOPC solution,re-spectively,through the corpus callosum.Survival,migration and differentiation of hOPC in the brain were observed by im-munofluorescence staining at 4 and 12 weeks after transplantation.Twelve weeks after transplantation,the effects of hOPC on mouse brain white matter were detected by immunofluorescence staining of myelin basic protein(MBP),myelin-associ-ated glycoprotein(MAG),neurofilament protein 200(NF200)and non-phosphorylated neurofilament H(using monoclo-nal antibody SMI32),and by water maze experiments.Paracrine signaling by hOPC was explored using immunofluores-cence staining for vascular endothelial growth factor(VEGF).RESULTS:The hOPC survived in the brains of VaD mice for 12 weeks,migrated to damaged white matter areas,and partially differentiated into mature oligodendrocytes(approxi-mately 64%).Twelve weeks after transplantation,hOPC significantly increased the fluorescence intensity of MBP,MAG,and NF200(P<0.05 or P<0.01)and decreased the fluorescence intensity of SMI32(P<0.01).The VEGF expression in hOPC-treated mice was significantly higher than that in sham and VaD groups(P<0.01).The difference in water maze test performance between hOPC and sham groups was not statistically significant(P>0.05).The mice in hOPC group had a shorter latency than those in VaD group(P<0.05 or P<0.01),and performed more platform crossings than those in VaD group(P<0.05).CONCLUSION:The hOPC can survive,migrate and differentiate in the brains of VaD mice,attenuate cerebral white matter lesions,and improve cognitive function.These improvements may be attributed to cell replacement and paracrine effects.

BACKGROUND:Oligodendrocyte precursor cells are seed cells for the treatment of white matter damage diseases.Establishing an efficient and stable in vitro differentiation method is an important prerequisite for clinical translational research.OBJECTIVE:To investigate the effect of fibronectin on biological characteristics such as proliferation,migration,and differentiation of oligodendrocyte precursor cells derived from human neural stem cells.METHODS:Human neural stem cells cultured in suspension were digested into single cells using Accutase.The expression of specific markers Nestin,Sox2,Vimentin,CD133,and Musashi was detected by flow cytometry.The single cells of human neural stem cells were resuspended in oligodendrocyte precursor cell medium and seeded in six-well plates coated with different concentrations of fibronectin(0,1,2.5,5,and 10 μg/mL).Accutase digestion was performed after 7 days of culture.Cells were counted by trypan staining.Fibronectin-coated group with the strongest amplification ability and the oligodendrocyte precursor cells without fibronectin-coated group were selected for further tests.The migration ability of the two groups of cells was detected by Transwell.Flow cytometry was used to detect the expression of Olig2,Sox10,and PDGFR-α.Oligodendrocyte precursor cells were induced to differentiate into oligodendrocytes for 3 weeks,and the expression of Galc in differentiated cells was detected by immunofluorescence staining.RESULTS AND CONCLUSION:(1)H uman neural stem cells grew in suspension spheres.Flow cytometry showed that human neural stem cells highly expressed Nestin,Sox2,Vimentin,CD133,and Musashi.(2)The cell bodies of oligodendrocyte precursor cells induced by human neural stem cells were round or oval,with strong refractive nature and bipolar or tertiary protrusions.Compared with the 0 μg/mL fibronectin coating group,there was a significant difference in the amplification ability of oligodendrocyte precursor cells in the 2.5,5,and 10 μg/mL fibronectin coating groups(P＜0.05).The amplification ability of oligodendrocyte precursor cells was the strongest when the fibronectin concentration was 10 μg/mL.(3)Flow cytometry results showed that the oligodendrocyte precursor cell markers 0Iig2,Sox10,and PDGFR-α were highly expressed in the 0 and 10 μg/mL fibronectin coating groups,and there was no significant difference between the two groups(P＞0.05).(4)Transwell chamber assay results showed that compared with the 0 μg/mL fibronectin-coated group,the migration ability of oligodendrocyte precursor cells in the 10 μg/mL fibronectin-coated group was increased(P＜0.01).(5)After 3 weeks of differentiation into oligodendrocytes,oligodendrocyte precursor cells showed complex morphology with multiple branches,grids or membrane sheets.Immunofluorescence staining results showed that there was no statistical difference in the Galc positive rate of oligodendrocytes between the two groups(P＞0.05).These findings indicate that when the concentration of fibronectin coated well plate is 10 μg/mL,the proliferation and migration of oligodendrocyte precursor cells are the strongest,but it does not affect the expression of oligodendrocyte precursor cells-specific markers Olig2,Sox10,and PDGFR-α and their differentiation into oligodendrocytes.

Objective:To develop a network-structured clinical pathway grouping rule based on the principles and methods of China healthcare security diagnosis related groups(CHS-DRG), for references for optimizing clinical pathway management.Methods:From August to November 2024, this study constructed a network-structured clinical pathway management framework, followed the grouping principles of CHS-DRG, and developed a network-structured clinical pathway grouping rule through literature analysis and expert discussions. 54 clinical specialists from the sample hospital were organized and grouped according to the rule for the normal magnification cases(139 218 cases) of DRG medical insurance settlement in the hospital in 2023. Using a stratified random sampling method, 205 physicians from 54 clinical specialties in the hospital were selected to quantitatively evaluate the rationality, homogeneity, and clarity of the grouping results. The Likert 5-level scoring method was wsed to assign scores.Results:The network-structured clinical pathway grouping rule and nomenclature was established. A total of 341 main pathways and 35 sub-pathways covering 169 adjacent diagnosis related groups were formed. The quantitative assessment scores for rationality, homogeneity, and clarity were 4.90, 4.87 and 4.87 points, respectively.Conclusions:The network-structured clinical pathway grouping rule based on CHS-DRG had good, feasibility and standardization, and could meet the practical needs of clinical applications.

OBJECTIVE: To investigate the efficacy of image-guided radioactive 125I seed (IGRIS) implantation for pelvic recurrent cervical cancer (PRCC) after external beam radiotherapy (EBRT), and analyze the influence of clinical and dosimetric factors on efficacy. METHODS: From July 2005 to October 2015, 36 patients with PRCC received IGRIS. We evaluated local progression-free survival (LPFS) and overall survival (OS). RESULTS: The median follow up was 11.5 months. The 1- and 2-year LPFS rate was 34.9% and 20%, respectively. The multivariate analysis indicated recurrence site (central or pelvic wall) (hazard ratio [HR]=0.294; 95% confidence interval [CI]=0.121–0.718), lesion volume (HR=2.898; 95% CI=1.139–7.372), D 90 (HR=0.332; 95% CI=0.130–0.850) were the independent factors affecting LPFS. The 1- and 2-year OS rate was 52.0% and 19.6%, respectively. The multivariate analysis suggested pathological type (HR=9.713; 95% CI=2.136–44.176) and recurrence site (HR=0.358; 95% CI=0.136–0.940) were the independent factors affecting OS. The dosimetric parameters of 33 patients mainly included D 90 (128.5±47.4 Gy), D 100 (50.4±23.7 Gy) and V 100 (86.7%±12.9%). When D 90 ≥105 Gy or D 100 ≥55 Gy or V 100 ≥91%, LPFS was extended significantly, but no significant difference for OS. The 79.2% of 24 patients with local pain were suffering from pain downgraded after radioactive 125I seed implantation. CONCLUSION: IGRIS implantation could be a safe and effective salvage treatment for PRCC after EBRT, which could markedly release the pain. Recurrence site, tumor volume and dose were the main factors affected efficacy. Compared with central recurrence, it was more suitable for patients with pelvic wall recurrent cervical cancer after EBRT.
Brachytherapy ; Disease-Free Survival ; Follow-Up Studies ; Humans ; Multivariate Analysis ; Radiometry ; Radiotherapy* ; Radiotherapy, Image-Guided ; Recurrence ; Salvage Therapy* ; Tumor Burden ; Uterine Cervical Neoplasms*

Objective To evaluate the efficacy and adverse effects of 125I seeds implantation for pelvic recurrence of cervical cancer (PRCC) after radiotherapy.Methods From July 2005 to October 2015,36 PRCC patients (median 44 years) after radiotherapy in Peking University Third Hospital were enrolled in this retrospective study.All patients underwent 125I seeds implantation under ultrasound or CT guidance.Treatment planning was performed before implantation to estimate the number and activity of 125I seeds.The seed numbers ranged from 10-140 (median:62.5),and the activity ranged from 18.5-29.6 (median:25.9) MBq.Postoperatively,the median dose delivered to 90％ gross tumor volume (D90) was 127.3 Gy.Kaplan-Meier method was used to calculate local progress free survival (LPFS) rate and overall survival (OS) rate,and log rank test and Cox regression were used for univariate and multivariate analyses.Results The median follow-up time was 11.5 months.The local control rate was 88.89％(32/36).The 1-year LPFS rate was 34.9％ and the 1-year OS rate was 52.0％.Thirty-one patients died,of which 22 (70.97％,22/31) died from cancer.Univariate analysis showed that the location of recurrence (x2=5.195),volume of lesion (hazard ratio (HR)=1.012) and D90(HR=0.988) were significantly correlated with LPFS (all P＜0.05).Multivariate analysis showed that the location of the recurrence was significantly related with LPFS (HR =0.215,P＜0.05).The 1-year LPFS rates of pelvic wall recurrence and central recurrence were 41.6％ and 26.7％ (x2 =5.195,P＜0.05),and 1-year OS rates were 54.7％ and 49.5％ (x2 =2.535,P＞0.05),respectively.Vaginal fistula,which may be caused by the treatment,occurred in 1 case.No other sever adverse effects were observed.Conclusions 125I seeds implantation is a safe and effective treatment for PRCC after radiotherapy.With the treatment of 125I seeds implantation,patients with pelvic wall recurrence may achieve better therapeutic effects than those with central recurrence.

Objective To determine the maximum tolerated dose ( MTD) and dose?limiting toxicity ( DLT) of weekly PTX and DDP concurrent postoperative radiotherapy in Chinese women with high?and intermediate?risk early cervical cancer. Methods Women with high risks postoperative cervical carcinoma, ECOG≤2 were eligible. Pelvis RT (6/10 MV X?ray,3DCRT 40 Gy/20f,para?metrial boost 10?20 Gy/5?10f) was followed by 2?4f brachytherapy applications ( 192 Ir,5 Gy/f) . Concurrent weekly chemotherapy was started at DDP 20 mg/m2 and PTX 10 mg/m2 weekly,and escalated in three?patient cohorts according to 3+3 methods. Results 25 patients were enrolled and treated over seven doses levels until dose?limiting toxicity (DLT) was reached. Median age was 48 years (range,34?66).All of patients finished RT in 7 weeks. Grade 3,4 non?hematologic toxicities were diarrhea and observed in two patients (4 cycles,DLT) at level 7.Grade 3,4 hematologic,principally leukopenia and neutropenia,and occurs late cycles. One grade 4 leukopenia and neutropenia was observed at dose level 6 but not seen in three additional patients. No one was delayed treatment time by concurrent chemotherapy.22 patients finished 6 cycles. Median follow?up is 59. 5 months. Three patients have died of cancer metastasis and recurrence. One patient has died of respiratory failure. Conclusions Combination PTX and DDP administered concurrently with pelvic EBRT can be safely administered at the MTD of DDP 35 mg/m2 and PTX 30 mg/m2 weekly for six cycles in Chinese women with postoperative cervical cancer.

Objective To assess the clinical efficacy of human neural stem cell (hNSC) transplantation in the treatment of severe cerebral palsy (CP) in children.Methods hNSCs were obtained from the forebrain of 10 to 12-week-fetus.Forty children with CP were voluntarily received hNSC transplantation that were injected into cerebral ventricle.The development of motor and fine motor functions were evaluated by GMFM and PDMS-FM 1 month before hNSC transplantation.as well as 3 and 6 months after hNSC transplantation.Results Twenty six (65％) cases displayed improvement from day 5 to month 6 after hNSC transplantation.GMFM assessment showed that the percentage was (4.52±2.50) ％ 1 month before hNSC transplantation,(7.74±2.94) ％ 3 months after hNSC transplantation and (13.01±6.71)％ 6 months after hNSC transplantation,indicating a significant improvement by the treatment of hNSC transplantation(P＜0.05).The percentage in PDMS-FM evaluation was (15.01± 12.00)％,(20.34± 11.91) ％ and (30.02± 12.50) ％ one month before hNSC transplantation,3 and 6 months after hNSC transplantation,respectively,also suggesting a significant improvement induced by hNSC transplantation treatment (P＜0.05).Moreover,the developmental improvement was the most prominent among 1-3 months post hNSC transplantation.Then the development slowed down.Significantly,patients received no hNSC transplantation experienced serious adverse events or complications.Conclusions hNSC transplantation is an effective and safer therapy for severe CP.Future observations are needed to evaluate long-term clinical efficacy of the therapy.