OBJECTIVES: To reprogram human placental fibroblasts (HPFs) into chemically induced epithelioid-like cells (ciEP-Ls) using a combination of small-molecule compounds. METHODS: HPFs cultured under normoxic conditions were identified using immunofluorescence assay, PCR and chromosomal karyotyping. Under hypoxic conditions (37 ℃, 5% O₂), HPFs were cultured in a medium containing small-molecule compounds C6TSEDRVAJZ (CHIR99021, 616452, TTNPB, SAG, EPZ5676, DZNep, Ruxolitinib, VTP50469, Afuresertib, JNK-IN-8, and EZM0414), and the cell morphology was observed daily. The expression levels of epithelial cell markers in the induced cells were detected by immunofluorescence, Western blotting and PCR. Chromosomal karyotyping of the induced cells was performed and the induction efficiency was calculated. RESULTS: Before induction, HPFs showed positive expressions of fibroblast surface markers CD34 and vimentin and were negative for epithelial surface markers. PCR results showed high expressions of fibroblast-specific genes S100A4 and COL1A1 in HPFs with a normal human diploid karyotype. After one day of induction, the HPFs underwent morphological changes from a multinodular spindle shape to a round or polygonal shape, which was morphologically characteristic of ciEP-Ls. On day 4 of induction, the cells exhibited high expressions of the epithelial cell markers E-cadherin and Lin28A. RT-qPCR results also showed that the cells expressed the epithelial markers Smad3, GLi3, PAX8, WT1, KRT19, and KRT18 with significantly down-regulated expressions of all the fibroblast surface markers and a normal human diploid karyotype. The reprogramming efficiency of HPFs into ciEP-Ls ranged from (64.53±2.8)% to (68.10±3.6)%. CONCLUSIONS The small-molecule compound combination C6TSEDRVAJZ is capable of inducing HPFs into ciEP-Ls under hypoxic conditions with a high induction efficiency.
Humans ; Fibroblasts/drug effects* ; Pregnancy ; Female ; Cell Differentiation/drug effects* ; Pyrimidines/pharmacology* ; Placenta/cytology* ; Cells, Cultured ; Pyridines/pharmacology* ; Pyrazoles/pharmacology* ; Epithelial Cells/cytology*

Objective To investigate the protective effects of butyrate on sepsis-related myocardial dys-function.Methods Thirty healthy 8-week-old male Sprague-Dawley rats were randomly divided into three groups:sham operation group(SH,n=10),sepsis group(CL,n=10),and butyrate group(BU,n=10).The CL and BU groups underwent cecal ligation and puncture(CLP)to establish sepsis models,while the SH group received the same surgical procedure without cecal ligation or puncture.Within 30 minutes post-opera-tion,the SH and CL groups received 5 mL normal saline via gavage,whereas the BU group was administered 5 mL sodium butyrate solution(500 mg/kg)in normal saline.Cardiac output(CO)and ejection fraction(EF)were compared among the three groups.Myocardial histopathological injury was assessed by HE staining,and mitochondrial ultrastructural damage was observed by electron microscopy.Serum levels of brain natriuretic peptide(BNP),cardiac troponin Ⅰ(cTnⅠ),and butyrate were compared among groups.Western blot analysis was performed to detect and compare the expression levels of long-chain acyl-CoA synthetase 4(ACSL4)and glutathione peroxidase 4(GPX4)in myocardial tissues.Results After intervention,the BNP and cTnⅠ levels in the CL group were higher than those in the SH group,while CO and EF were lower than those in the SH group(P＜0.05).The BNP and cTnⅠ levels in the BU group were lower than those in the CL group,whereas CO and EF levels were higher than those in the CL group(P＜0.05).HE staining of myocardial tissues re-vealed more severe inflammatory cell infiltration and myocardial cell edema in the CL group compared with the SH group,while the BU group showed reduced inflammatory cell infiltration.Mitochondrial membrane in-tegrity was impaired in the CL group manifested by unclear cristae,swelling,vacuolar degeneration and rup-ture,whereas mitochondrial damage was attenuated in the BU group.Serum butyrate levels were measured as(61.7±21.6)μg/mL,(95.3±16.6)μg/mL and(302.2±49.7)μg/mL in the CL,SH and BU groups respec-tively(P＜0.05).The ACSL4 expression in the CL group was higher than that in the SH group,while GPX4 protein expression was lower than that in the SH group(P＜0.05).The BU group exhibited lower ACSL4 expression and higher GPX4 protein expression compared with the CL group(P＜0.05).Conclusion Buty-rate can ameliorate myocardial injury in septic rats,and its protective effect may be associated with the inhibi-tion of myocardial ferroptosis.

Objective·To observe the impact of hip synovitis on the long-term outcomes of free vascularized fibular grafting(FVFG)for osteonecrosis of femoral head(ONFH).Methods·Between October 2001 and December 2013,370 patients diagnosed with ONFH(556 hips)underwent FVFG.Preoperative synovitis was assessed using magnetic resonance imaging(MRI)and quantified with the Hip Inflammation MRI Scoring System(HIMRISS).Patients were divided into no synovitis group,moderate synovitis group,and severe synovitis group.Harris hip scores and the incidence of total hip arthroplasty were collected with an average follow-up duration of 90.5 months(range:5-215 months).Hip survival failure(defined as a Harris hip score lower than 80 at the final follow-up or the occurrence of total hip arthroplasty)was calculated.Multivariable Cox regression analysis was adopted to compare the influence of different degrees of synovial inflammation on long-term prognosis.Results·The proportion of hip survival failure was 28.0％in patients without synovitis and 28.5％in those with moderate synovitis,whereas it was significantly higher(60.4％)in patients with severe synovitis.The results of multivariable Cox regression analysis showed that severe synovitis was an independent risk factor for poor prognosis(HR 2.06,95％CI 1.21-3.53)after adjusting for age,gender,education level,marital status,ONFH type,affected side of ONFH,smoking history,baseline Harris hip score and other hip MRI-based covariates(collapse,bone marrow edema,and degeneration).Conclusion·Severe synovitis in patients with ONFH significantly increases the failure rate of hip preservation after FVFG,and the severity of synovitis should be considered in surgical decision-making.

Paraplegia caused by spinal cord injury is a serious neurological complication, for which surgery is currently the main treatment method. Due to different surgical approaches, patients are usually expected to maintain a passive prone position for a long time or switch between the supine and prone positions. Affected by multiple factors such as neurogenic sensory disorders, pathological changes in muscle tone and operative duration, the risk of intraoperative acquired pressure injury (IAPI) is significantly increased. Current clinical prevention strategies for IAPI in these patients predominantly focus on localized pressure relief during positioning, lacking systematic, standardized comprehensive prevention protocols or evidence-based guidelines. To address it, Department of Nursing, Orthopedics Branch, China International Exchange and Promotive Association for Medical and Health Care, Spinal Trauma Professional Committee, Orthopedics Branch, Chinese Medical Doctor Association, Nursing Group of Spine and Spinal Cord Professional Committee of Chinese Association of Rehabilitation Medicine organized experts in relevant fields to formulate Guideline for the prevention of intraoperative acquired pressure injury in paraplegic patients with spinal cord injury ( version 2025), based on evidence-based medical evidence and latest research results and clinical practice at home and abroad. Eleven recommendations were put forward from the aspects of preoperative risk assessment, intraoperative prevention strategies, postoperative handover and monitoring, and supportive mechanisms for IAPI prevention, aiming to standardize the prevention measures and management strategies of IAPI in paraplegic patients with spinal cord injury and accelerate the recovery of patients and improve the therapeutic effect.

Vertebral refracture following percutaneous vertebral augmentation (PVA) is commonly seen in elderly patients with osteoporotic thoracolumbar compression fractures (OTLCF). It can lead to recurrent pain, loss of vertebral height, progression of kyphosis, and even neurological dysfunction, significantly impairing patients′ quality of life. Current diagnosis and treatment face multiple challenges, including high misdiagnosis rate, difficulty in choosing between surgical and non-surgical treatment options, lack of standardized surgical protocols, interference from intralesional bone cement during procedures, inadequate stability of internal fixation in osteoporotic bone, and suboptimal compliance of anti-osteoporotic therapy. Establishing a standardized diagnostic and therapeutic framework is urgently needed. To standardize the management process and improve outcomes for vertebral refractures after PVA in elderly OTLCF patients, Spinal Trauma Group of the Orthopedic Branch of Chinese Medical Doctor Association organized experts in the field to develop Guideline for the diagnosis and treatment of vertebral refracture after percutaneous vertebral augmentation in elderly patients with osteoporotic thoracolumbar compression fractures ( version 2025), based on current literature and clinical experience, and adhering to principles of scientific rigor and clinical applicability. A total of 11 recommendations were proposed, encompassing diagnosis, treatment, and rehabilitation of vertebral refracture after PVA in elderly patients with OTLCF, aiming to provide a foundation for a standardized management.

Fetal malformation of cortical development(MCD)is a group of structural neurological disorders caused by abnormalities in development of cortical layer during embryogenesis,characterized by significant heterogeneity and diversity,which may lead to adverse clinical outcomes such as epilepsy and intellectual disabilities.The progresses in prenatal evaluation on fetal MCD were reviewed in this article.

Objective To investigate the effect of unilateral or bilateral transcranial direct current stimulation(tDCS)on post-stroke dysphagia.Methods From February,2023 to March,2025,27 stroke patients with dysphagia and nasal feeding in Beijing Bo'ai Hos-pital were randomly divided into healthy side stimulation group,bilateral stimulation group and sham stimulation group,with nine cases in each group.All the groups received conventional swallowing training and tDCS,while the healthy side stimulation group stimulated on the healthy side of oropharyngeal cortex;and the bilateral stimu-lation group alternatively stimulated bilateral oropharyngeal cortex,with one hour interval between bilateral stim-ulation;the sham stimulation group stimulated the healthy side of oropharyngeal cortex for 30 seconds and then stop.The course lasted two weeks.The scores of Standard Swallowing Function Assessment Scale(SSA),Modi-fied Mann Assessment of Swallowing Ability(MMASA)and Rosenbek Penetration-Aspiration Scale(PAS)were compared before and after treatment.Results The intra-group effect(F=16.185,P<0.01)was significant in the scores of SSA,the intra-group effect(F=28.650,P<0.01)and interaction effect(F=3.453,P<0.01)were significant in the scores of MMASA,and there was no significant difference in the inter-group effect,intra-group effect and interaction effect in the scores of PAS(P>0.05).Post hoc test showed that there was no significant difference in the scores of SSA,MMASA and PAS among three groups(P>0.05).There was significant difference in the score difference of MMASA be-fore and after treatment among three groups(F=4.698,P<0.05).Post hoc test showed that the score difference of MMAS was more in the healthy side stimulation group than in the bilateral stimulation group and the sham stimulation group(P<0.05),with no significant difference between the bilateral stimulation group and the sham stimulation group(P>0.05).Conclusion tDCS can partly improve post-stroke dysphagia.The healthy side anode stimulation is superior to the alter-nating bilateral hemisphere anode stimulation.

Fetal malformation of cortical development(MCD)is a group of structural neurological disorders caused by abnormalities in development of cortical layer during embryogenesis,characterized by significant heterogeneity and diversity,which may lead to adverse clinical outcomes such as epilepsy and intellectual disabilities.The progresses in prenatal evaluation on fetal MCD were reviewed in this article.

Objective To investigate the effect of unilateral or bilateral transcranial direct current stimulation(tDCS)on post-stroke dysphagia.Methods From February,2023 to March,2025,27 stroke patients with dysphagia and nasal feeding in Beijing Bo'ai Hos-pital were randomly divided into healthy side stimulation group,bilateral stimulation group and sham stimulation group,with nine cases in each group.All the groups received conventional swallowing training and tDCS,while the healthy side stimulation group stimulated on the healthy side of oropharyngeal cortex;and the bilateral stimu-lation group alternatively stimulated bilateral oropharyngeal cortex,with one hour interval between bilateral stim-ulation;the sham stimulation group stimulated the healthy side of oropharyngeal cortex for 30 seconds and then stop.The course lasted two weeks.The scores of Standard Swallowing Function Assessment Scale(SSA),Modi-fied Mann Assessment of Swallowing Ability(MMASA)and Rosenbek Penetration-Aspiration Scale(PAS)were compared before and after treatment.Results The intra-group effect(F=16.185,P<0.01)was significant in the scores of SSA,the intra-group effect(F=28.650,P<0.01)and interaction effect(F=3.453,P<0.01)were significant in the scores of MMASA,and there was no significant difference in the inter-group effect,intra-group effect and interaction effect in the scores of PAS(P>0.05).Post hoc test showed that there was no significant difference in the scores of SSA,MMASA and PAS among three groups(P>0.05).There was significant difference in the score difference of MMASA be-fore and after treatment among three groups(F=4.698,P<0.05).Post hoc test showed that the score difference of MMAS was more in the healthy side stimulation group than in the bilateral stimulation group and the sham stimulation group(P<0.05),with no significant difference between the bilateral stimulation group and the sham stimulation group(P>0.05).Conclusion tDCS can partly improve post-stroke dysphagia.The healthy side anode stimulation is superior to the alter-nating bilateral hemisphere anode stimulation.

Objective·To observe the impact of hip synovitis on the long-term outcomes of free vascularized fibular grafting(FVFG)for osteonecrosis of femoral head(ONFH).Methods·Between October 2001 and December 2013,370 patients diagnosed with ONFH(556 hips)underwent FVFG.Preoperative synovitis was assessed using magnetic resonance imaging(MRI)and quantified with the Hip Inflammation MRI Scoring System(HIMRISS).Patients were divided into no synovitis group,moderate synovitis group,and severe synovitis group.Harris hip scores and the incidence of total hip arthroplasty were collected with an average follow-up duration of 90.5 months(range:5-215 months).Hip survival failure(defined as a Harris hip score lower than 80 at the final follow-up or the occurrence of total hip arthroplasty)was calculated.Multivariable Cox regression analysis was adopted to compare the influence of different degrees of synovial inflammation on long-term prognosis.Results·The proportion of hip survival failure was 28.0％in patients without synovitis and 28.5％in those with moderate synovitis,whereas it was significantly higher(60.4％)in patients with severe synovitis.The results of multivariable Cox regression analysis showed that severe synovitis was an independent risk factor for poor prognosis(HR 2.06,95％CI 1.21-3.53)after adjusting for age,gender,education level,marital status,ONFH type,affected side of ONFH,smoking history,baseline Harris hip score and other hip MRI-based covariates(collapse,bone marrow edema,and degeneration).Conclusion·Severe synovitis in patients with ONFH significantly increases the failure rate of hip preservation after FVFG,and the severity of synovitis should be considered in surgical decision-making.