Objective:To compare the biomechanical differences among modular total sacral prosthesis, integrated total sacral prosthesis and screw-rod system for lumbosacral reconstruction after total sacrectomy by finite element analysis.Methods:Three finite element models of reconstruction after total sacrectomy were established: six-rod plus anterior column, integrated total sacral prosthesis, and modular total sacral prosthesis. A vertical load of 600 N was applied to the L 3 vertebra, and the bilateral acetabula were fixed in all degrees of freedom to restrict their movement, simulating a bipedal standing posture. The maximum stress, stress distribution on the iliac screws, stress distribution on the longitudinal rods, the shift-down displacement of the L 5 vertebra, and the stress direction on the contact surface between the prosthesis and the ilium on all implant components (including prosthesis, screws, and connecting rods) were compared. Results:Finite element analysis results show that the average maximum stress of the six-rod plus anterior column reconstruction on all implant instrumentation was 217.9±10.2 MPa, the integrated total sacral prosthesis reconstruction was 185.7±21.1 MPa, and the modular total sacral prosthesis reconstruction was 157.4±31.2 MPa. The differences were statistically significant ( F=12.357, P<0.001). Among them, the difference between the modular total sacral prosthesis reconstruction and the six-rod plus anterior column reconstruction was statistically significant ( P<0.001), while the difference between the modular total sacral prosthesis reconstruction and the integrated total sacral prosthesis reconstruction was not statistically significant ( P=0.051). The maximum stress on the iliac bone screws and longitudinal connecting rods: for the six-rod plus anterior column reconstruction, it was 157.2 MPa and 105.4 MPa respectively; for the integrated total sacral prosthesis reconstruction, it was 59.2 MPa and 97.8 MPa respectively; for the modular total sacral prosthesis reconstruction, it was 58.4 MPa and 35.6 MPa respectively. The distance of L 5 vertebral body downward displacement: for the six-rod plus anterior column reconstruction, it was 1.05±0.06 mm; for the integrated total sacral prosthesis reconstruction, it was 0.34±0.02 mm; for the modular total sacral prosthesis reconstruction, it was 0.40±0.05 mm. The difference was statistically significant ( F=357.730, P<0.001), among which the differences between the modular total sacral prosthesis reconstruction and the six-rod plus anterior column reconstruction and that between the integrated total sacral prosthesis reconstruction and the six-rod plus anterior column reconstruction were all statistically significant ( P<0.05), while the difference between the modular total sacral prosthesis reconstruction and the integrated total sacral prosthesis reconstruction was not statistically significant ( P=0.145). The stress on the iliac bone contact surface of the integrated total sacral prosthesis was 34.2° and manifested as shear force; the stress on the iliac bone contact surface of the modular total sacral prosthesis was 88.9° and manifested as compressive stress. Conclusions:This modular total sacral prosthesis exhibits lower peak stress compared with the integrated total sacral prosthesis and screw-rod system. The spinal stability of the modular total sacral prosthesis is comparable to that of the integrated total sacral prosthesis and superior to that of the screw-rod system.

Objective:To compare the biomechanical differences among modular total sacral prosthesis, integrated total sacral prosthesis and screw-rod system for lumbosacral reconstruction after total sacrectomy by finite element analysis.Methods:Three finite element models of reconstruction after total sacrectomy were established: six-rod plus anterior column, integrated total sacral prosthesis, and modular total sacral prosthesis. A vertical load of 600 N was applied to the L 3 vertebra, and the bilateral acetabula were fixed in all degrees of freedom to restrict their movement, simulating a bipedal standing posture. The maximum stress, stress distribution on the iliac screws, stress distribution on the longitudinal rods, the shift-down displacement of the L 5 vertebra, and the stress direction on the contact surface between the prosthesis and the ilium on all implant components (including prosthesis, screws, and connecting rods) were compared. Results:Finite element analysis results show that the average maximum stress of the six-rod plus anterior column reconstruction on all implant instrumentation was 217.9±10.2 MPa, the integrated total sacral prosthesis reconstruction was 185.7±21.1 MPa, and the modular total sacral prosthesis reconstruction was 157.4±31.2 MPa. The differences were statistically significant ( F=12.357, P<0.001). Among them, the difference between the modular total sacral prosthesis reconstruction and the six-rod plus anterior column reconstruction was statistically significant ( P<0.001), while the difference between the modular total sacral prosthesis reconstruction and the integrated total sacral prosthesis reconstruction was not statistically significant ( P=0.051). The maximum stress on the iliac bone screws and longitudinal connecting rods: for the six-rod plus anterior column reconstruction, it was 157.2 MPa and 105.4 MPa respectively; for the integrated total sacral prosthesis reconstruction, it was 59.2 MPa and 97.8 MPa respectively; for the modular total sacral prosthesis reconstruction, it was 58.4 MPa and 35.6 MPa respectively. The distance of L 5 vertebral body downward displacement: for the six-rod plus anterior column reconstruction, it was 1.05±0.06 mm; for the integrated total sacral prosthesis reconstruction, it was 0.34±0.02 mm; for the modular total sacral prosthesis reconstruction, it was 0.40±0.05 mm. The difference was statistically significant ( F=357.730, P<0.001), among which the differences between the modular total sacral prosthesis reconstruction and the six-rod plus anterior column reconstruction and that between the integrated total sacral prosthesis reconstruction and the six-rod plus anterior column reconstruction were all statistically significant ( P<0.05), while the difference between the modular total sacral prosthesis reconstruction and the integrated total sacral prosthesis reconstruction was not statistically significant ( P=0.145). The stress on the iliac bone contact surface of the integrated total sacral prosthesis was 34.2° and manifested as shear force; the stress on the iliac bone contact surface of the modular total sacral prosthesis was 88.9° and manifested as compressive stress. Conclusions:This modular total sacral prosthesis exhibits lower peak stress compared with the integrated total sacral prosthesis and screw-rod system. The spinal stability of the modular total sacral prosthesis is comparable to that of the integrated total sacral prosthesis and superior to that of the screw-rod system.

Objective:To investigate the clinical and genetic features of patients with spastic paraplegia and psychomotor retardation with or without seizures (SPPRS) caused by HACE1 gene mutation. Methods:Clinical data, auxiliary examination and genetic test results of a child with SPPRS caused by HACE1 gene mutation who was admitted to Henan Children′s Hospital in April 2019 were collected. The clinical and genotypic characteristics of children with SPPRS were summarized by searching the relevant literature up to June 2024, retrieved from CNKI, Wanfang and PubMed databases with the terms of " HACE1" "SPPRS" "seizures" "spastic paraplegia". Results:The patient was a 11 months and 20 days old male, with a clinical phenotype including global developmental delay, leg spastic tremor, frequent epileptic seizures, obesity, and concurrent urethral malformation. Brain magnetic resonance imaging (MRI) showed enlarged bilateral ventricles, hypoplastic corpus callosum, delayed myelination. Genetic test results revealed compound heterozygous variants c.994C>T (p.R332 *) and c.1679-2A>G in the HACE1 gene (according to the transcript NM_020771), respectively inherited from his mother and father, with c.1679-2A>G being a newly reported variant. A total of 6 English literatures reported 21 SPPRS patients in 11 families, and HACE1 gene mutations were mainly characterized by nonsense mutations. The main clinical manifestations included global developmental delay (21 cases), movement disorders (21 cases), intellectual disabilities (18 cases), seizures (13 cases), obesity (13 cases), skeletal abnormalities (11 cases), microcephaly (9 cases), ocular abnormalities (9 cases), distinctive facial features (5 cases), sensorineural hearing loss (5 cases), and short stature (3 cases). MRI predominantly showed hypoplasia of the corpus callosum, ventricular dilation, paucity of white matter and cerebral atrophy. There were no clear genotype-phenotype correlations. A total of 13 HACE1 gene mutations were reported, including 9 nonsense mutations, 2 frameshift mutations, 1 in-frame mutation, and 1 missense mutation. Among the 11 families, only 2 families with 5 patients were caused by compound heterozygous mutations, c.1852_1853del (p.L832del) and c.454C>T (p.Q152 *), c.2242C>T (p.R748 *) and c.2019_2020insTTTAGGTATTTTTAGGTATT (p.P674fs). The other 16 patients in 9 families were caused by homozygous mutations of the remaining 9 mutations. Conclusions:SPPRS is rare and usually occurs in infancy. The main clinical manifestations include comprehensive developmental delay, movement disorders, epilepsy, etc. Currently, no clear genotype-phenotype correlation has been found. The c.1679-2A>G variant of the HACE1 gene is an unreported variant and enriches the mutation spectrum of the HACE1 gene.

ObjectiveThe antitumor activity of sesquiterpenoid M36 isolated from Myrrha against human hepatoma HepG2 cells was investigated in this study. MethodHepG2 cells were treated with M36 at different concentrations （0， 2， 4， 6， 8， 10 μmol·L^-1）. Firstly， the effects of M36 on the proliferation of human hepatoma HepG2 cells were detected by methyl thiazolyl tetrazolium （MTT）， colony formation assay， and EdU proliferation assay. Hoechst staining， flow cytometry analysis， and Western blot were used to explore the effect of M36 on the apoptosis of human hepatoma HepG2 cells. Acridine orange staining and western blotting were used to examine the effect of M36 on autophagy in HepG2 cells. Finally， Western blot was used to detect protein expression of cancer-related signaling pathways. ResultCompared with the blank group， M36 treatment significantly inhibited the proliferation of human hepatoma HepG2 cells （P<0.01）， and the half inhibitory concentration （IC₅₀） value of M36 for 48 h was 5.03 μmol·L^-1， in a dose- and time-dependent manner. M36 was also able to induce apoptosis and autophagy in human hepatoma HepG2 cells. After treatment with 8 μmol·L^-1 M36 for 48 hours， the apoptosis rate of HepG2 cells was （42.03±9.65）% （P<0.01）. Compared with the blank group， HepG2 cells treated with 4 and 8 μmol·L^-1 M36 for 48 h had a significant increase in cleaved poly ADP-ribose polymerase （cleaved-PARP） protein levels （P<0.01）. Acridine orange staining showed that autophagy was significantly activated in HepG2 cells treated with 4 and 8 μmol·L^-1 M36 for 48 h compared with the blank group （P<0.01）， which was further verified by the up-regulation of microtubule-associated protein 1 light chain 3 Ⅱ （LC3 Ⅱ）. Western blot results showed that compared with the blank group， the levels of phosphorylated extracellular regulated protein kinase （p-ERK）， phosphorylated p38 mitogen-activated protein kinase （p-p38 MAPK）， phosphorylated c-Jun N-terminal kinase （p-JNK）， and its downstream nuclear transcription factors c-Jun and p-c-Jun protein were significantly increased in M36 group （P<0.05， P<0.01）. The mechanism may be related to the up-regulation of MAPK signaling pathway. ConclusionThe sesquiterpenoid M36 isolated from Myrrha inhibits the proliferation of human hepatoma HepG2 cells and promotes apoptosis and autophagy， which may be related to the activation of the MAPK signaling pathway.

Objective To explore the correlation between the characteristics of left atrial(LA)strain and exercise endurance in patients with chronic heart failure(CHF).Methods A total of 212 CHF patients admitted to our hospital from November 2021 to January 2023 were prospec-tively subjected in this study.According to their maximal oxygen uptake(VO2max),they were di-vided into high endurance group[≥16 ml/(kg·min),125 cases]and low endurance group[＜16 ml/(kg·min),125 cases].The general data and results of laboratory test were analyzed and com-pared between the two groups.Logistic regression analysis was used to analyze the related factors affecting the exercise endurance.Results Significant differences were observed between the two groups in level of NT-proBNP,ratio of early diastolic peak velocity of mitral valve(E)to early di-astolic peak velocity of mitral annulus(e'),E,LVEDVI,LVESVI,LVSVI,LVEF,LVGLS,LA maximum volume index(LAVImax),LA minimum volume index(LAVImin),LA reservoir strain(LASr),LA conduit strain duct strain(LAScd),and LA contractile strain(LASct)(P＜0.05).Multivariate logistic regression analysis showed that LASr(OR=0.987,95％CI:1.003-1.029),LAScd(OR=1.177,95％CI:0.688-0.955),LASct(OR=1.341,95％CI:0.507-0.884).NT-proBNP(OR=1.002,95％CI:0.995-1.000),E/e'(OR=1.086,95％CI:1.000-1.183),LVEDVI(OR=1.127,95％CI:0.805-0.936)and LVEF(OR=0.909,95％CI:0.824-1.000)were related factors influencing exercise endurance in CHF patients(P＜0.05).Restricted cube chart revealed that there was a significant nonlinear relationship between LASr,LAScd and LASct and exercise endurance in the patients(x2=9.830,16.820,9.080,P＜0.05).Conclusion The char-acteristic indicators of LA strain are related to exercise endurance of CHF patients.

Objective Kisspeptin,a protein encoded by the KISS1 gene,functions as an essential factor in suppressing tumor growth.The intricate orchestration of cellular processes such as proliferation and differentiation is governed by the Notch1/Akt/Foxo1 signaling pathway,which assumes a central role in maintaining cellular homeostasis.In the specific context of this investigation,the focal point lies in a meticulous exploration of the intricate mechanisms underlying the regulatory effect of kisspeptin on the process of endometrial decidualization.This investigation delves into the interplay between kisspeptin and the Notch1/Akt/Foxo1 signaling pathway,aiming to elucidate its significance in the pathophysiology of recurrent spontaneous abortion(RSA).Methods We enrolled a cohort comprising 45 individuals diagnosed with RSA,who were admitted to the outpatient clinic of the Reproductive Center at the Second Affiliated Hospital of Soochow University between June 2020 and December 2020.On the other hand,an additional group of 50 women undergoing elective abortion at the outpatient clinic of the Family Planning Department during the same timeframe was also included.To comprehensively assess the molecular landscape,Western blot and RT-qPCR were performed to analyze the expression levels of kisspeptin(and its gene KISS1),IGFBP1(an established marker of decidualization),Notch1,Akt,and Foxo1 within the decidua.Human endometrial stromal cells(hESC)were given targeted interventions,including treatment with siRNA to disrupt KISS1 or exposure to kisspeptin10(the bioactive fragment of kisspeptin),and were subsequently designated as the siKP group or the KP10 group,respectively.A control group comprised hESC was transfected with blank siRNA,and cell proliferation was meticulously evaluated with CCK8 assay.Following in vitro induction for decidualization across the three experimental groups,immunofluorescence assay was performed to identify differences in Notch1 expression and decidualization morphology between the siKP and the KP10 groups.Furthermore,RT-qPCR and Western blot were performed to gauge the expression levels of IGFBP1,Notch1,Akt,and Foxo1 across the three cell groups.Subsequently,decidualization was induced in hESC by adding inhibitors targeting Notch1,Akt,and Foxo1.The expression profiles of the aforementioned proteins and genes in the four groups were then examined,with hESC induced for decidualization without adding inhibitors serving as the normal control group.To establish murine models of normal pregnancy(NP)and RSA,CBA/J×BALB/c and CBA/J×DBA/2 mice were used.The mice were respectively labeled as the NP model and RSA model.The experimental groups received intraperitoneal injections of kisspeptin10 and kisspeptin234(acting as a blocker)and were designated as RSA-KP10 and NP-KP234 groups.On the other hand,the control groups received intraperitoneal injections of normal saline(NS)and were referred to as RSA-NS and NP-NS groups.Each group comprised 6 mice,and uterine tissues from embryos at 9.5 days of gestation were meticulously collected for observation of embryo absorption and examination of the expression of the aforementioned proteins and genes.Results The analysis revealed that the expression levels of kisspeptin,IGFBP1,Notch1,Akt,and Foxo1 were significantly lower in patients diagnosed with RSA compared to those in women with NP(P<0.01 for kisspeptin and P<0.05 for IGFBP1,Notch1,Akt,and Foxo1).After the introduction of kisspeptin10 to hESC,there was an observed enhancement in decidualization capability.Subsequently,the expression levels of Notch1,Akt,and Foxo1 showed an increase,but they decreased after interference with KISS1.Through immunofluorescence analysis,it was observed that proliferative hESC displayed a slender morphology,but they transitioned to a rounder and larger morphology post-decidualization.Concurrently,the expression of Notch1 increased,suggesting enhanced decidualization upon the administration of kisspeptin10,but the expression decreased after interference with KISS1.Further experimentation involved treating hESC with inhibitors specific to Notch1,Akt,and Foxo1 separately,revealing a regulatory sequence of Notch1/Akt/Foxo1(P<0.05).In comparison to the NS group,NP mice administered with kisspeptin234 exhibited increased fetal absorption rates(P<0.001)and decreased expression of IGFBP1,Notch1,Akt,and Foxo1(P<0.05).Conversely,RSA mice administered with kisspeptin10 demonstrated decreased fetal absorption rates(P<0.001)and increased expression levels of the aforementioned molecules(P<0.05).Conclusion It is suggested that kisspeptin might exert its regulatory influence on the process of decidualization through the modulation of the Notch1/Akt/Foxo1 signaling cascade.A down-regulation of the expression levels of kisspeptin could result in suboptimal decidualization,which in turn might contribute to the development or progression of RSA.

OBJECTIVE: To develop the clinical questions and outcomes of Clinical Practice Guideline of Fire Needling Therapy for Herpes Zosters based on Norms of Formulation and Evaluation for the Clinical Guideline on Acupuncture and Moxibustion released by World Federation of Acupuncture and Moxibustion Societies. METHODS: Combined the investigation with expert consultation and consensus method, and taken clinicians (members) of Chinese Association of Acupuncture and Moxibustion as the subjects, the clinical questions concerned were collected and the two-round consultation was conducted among expert group by letter. In the first round questionnaire, using the voting method, the relevant clinical questions in intervention measures were collected; and in the second round, with the Delphi method adopted, the importance of clinical questions and outcomes in the investigation was scored. RESULTS: A total of 200 structured clinical questions proposed by 153 clinicians and the clinical experience with 13 kinds of combined therapies involved and fire needling as the key measure were collected. The authority coefficient (Cr) of the Delphi questionnaire was >0.70, and the coefficient of variation for the importance scores of alternative clinical questions and outcomes was 0.06-0.26 and 0.12-0.47, respectively. The top 10 clinical questions and 12 outcomes (6 outcomes referred to the patients either in the acute stage or the post-neuralgia stage) were included, with the importance score of clinical questions>4, the importance score of outcomes>6, and the coefficient of variation ≤0.25. CONCLUSION The clinical questions and outcomes of Clinical Practice Guideline of Fire Needling Therapy for Herpes Zosters are formulated, which provides the research basis for the recommendation development of the guideline.
Acupuncture Therapy/methods* ; Treatment Outcome ; Practice Guidelines as Topic ; Herpes Zoster/therapy* ; Humans ; Delphi Technique

Objective:To explore the clinical phenotype and genetic characteristics of a Chinese pedigree affected with Spastic paraplegia type 5A (SPG5A).Methods:A pedigree suspected for Hereditary spastic paraplegia (HSP) at Henan Children′s Hospital on August 15 2022 was selected as the study subject. Clinical data of the pedigree was collected. Peripheral blood samples were collected from members of the pedigree. Following extraction of genomic DNA, trio-WGS was carried out, and candidate variant was verified by Sanger sequencing.Results:The child, a 1-year-old boy, had presented with microcephaly, hairy face and dorsal side of distal extremities and trunk, intellectual and motor development delay, increased muscle tone of lower limbs, hyperreflexes of bilateral knee tendons, and positive pathological signs. His parents and sister both had normal phenotypes. Trio-WGS revealed that the child has harbored a homozygous c. 1250G>A (p.Arg417His) variant of the CYP7B1 gene, for which his mother was heterozygous, the father and sister were of the wild type. The variant was determined to have originated from maternal uniparental disomy (UPD). The result of Sanger sequencing was in keeping with the that of trio-WGS. SPG5A due to maternal UPD of chromosome 8 was unreported previously. Conclusion:The child was diagnosed with SPG5A, a complex type of HSP, for which the homozygous c. 1250G>A variant of the CYP7B1 gene derived from maternal UPD may be accountable.

Objective:To investigate the risk factors of early death after lung transplantation in patients with idiopathic pulmonary fibrosis (IPF) complicated with pulmonary arterial hypertension (PAH).Methods:A retrospective cohort study was conducted. The clinical data of 134 patients with IPF and PAH who underwent lung transplantation at Wuxi People's Hospital Affiliated to Nanjing Medical University from January 2017 to December 2020 were collected. The donor's gender, age, duration of mechanical ventilation, and cold ischemia time, the recipient's gender, age, body mass index (BMI), smoking, history of hypertension and diabetes, preoperative usage of hormones, mean pulmonary arterial pressure (mPAP), cardiac echocardiography and cardiac function, serum creatinine (SCr), N-terminal pro-brain natriuretic peptide (NT-proBNP) as well as surgical type, extracorporeal membrane oxygenation (ECMO) treatment, duration of operation, and plasma and red blood cell infusion ratio were collected. The cumulative survival rates of patients at 30, 60, and 180 days after lung transplantation were calculated by Kaplan-Meier method. The univariate and multivariate Cox proportional hazards regression models were used to analyze the effects of donor, recipient, and surgical factors on early survival in donors after lung transplantation.Results:The majority of donors were male (80.6%). There was 63.4% of the donors older than 35 years old, 80.6% of the donors had mechanical ventilation duration less than 10 days, and the median cold ischemia time was 465.00 (369.25, 556.25) minutes. The recipients were mainly males (83.6%). Most of the patients were younger than 65 years old (70.9%). Most of them had no hypertension (75.4%) or diabetes (67.9%). The median mPAP of recipients was 36 (30, 43) mmHg (1 mmHg≈0.133 kPa). There were 73 patients with single lung transplantation (54.5%), and 61 with double lung transplantation (45.5%). The survival rates of 134 IPF patients with PAH at 30, 60, 180 days after lung transplantation were 81.3%, 76.9%, and 67.4%, respectively. Univariate Cox proportional risk regression analysis showed that recipient preoperative use of hormone [hazard ratio ( HR) = 2.079, 95% confidence interval (95% CI) was 1.048-4.128], mPAP ≥ 35 mmHg ( HR = 2.136, 95% CI was 1.129-4.044), NT-proBNP ≥ 300 ng/L ( HR = 2.411, 95% CI was 1.323-4.392), New York Heart Association (NYHA) cardiac function classification Ⅲ-Ⅳ ( HR = 3.021, 95% CI was 1.652-5.523) were the risk factors of early postoperative death in patients with IPF complicated with PAH (all P < 0.05). In the multivariable Cox proportional risk regression analysis, recipient preoperative hormone usage (model 1: HR = 2.072, 95% CI was 1.044-4.114, P = 0.037; model 2: HR = 2.098, 95% CI was 1.057-4.165, P = 0.034), NT-proBNP ≥ 300 ng/L ( HR = 2.246, 95% CI was 1.225-4.116, P = 0.009) and NYHA cardiac function classification Ⅲ-Ⅳ ( HR = 2.771, 95% CI was 1.495-5.134, P = 0.001) were independent risk factors of early postoperative death in patients with IPF. Conclusions:Preoperative hormone usage, NT-proBNP ≥ 300 ng/L, NYHA cardiac function classification Ⅲ-Ⅳ are independent risk factors for early death in patients with IPF and PAH after lung transplantation. For these patients, attention should be paid to optimize their functional status before operation. Preoperative reduction of receptor hormone usage and improvement of cardiac function can improve the early survival rate of such patients after lung transplantation.

OBJECTIVE: To explore the clinical and genetic characteristics of four patients with medium-chain acyl-CoA dehydrogenase deficiency (MCADD). METHODS: Four children who had presented at the Children's Hospital Affiliated to Zhengzhou University between August 2019 and August 2021 were selected as the study subjects. Clinical data of the children were collected. The children were subjected to whole exome sequencing (WES). RESULTS: All of the four children were diagnosed with MCADD. Blood amino acid and ester acyl carnitine spectrum test showed that the concentration of octanoyl carnitine (C8) was significantly increased. The main clinical manifestations included poor mental response (3 cases), intermittent diarrhea with abdominal pain (1 case), vomiting (1 case), increased transaminase (3 cases), and metabolic acidosis (2 cases). Five variants were identified by genetic testing, among which c.341A>G (p.Y114C) was unreported previously. Three were missense variants, one was frameshift variant and one was splicing variant. CONCLUSION The clinical heterogeneity of MCADD is obvious, and the severity of the disease may vary. WES can assist with the diagnosis. Delineation of the clinical symptoms and genetic characteristics of the disease can facilitate early diagnosis and treatment of the disease.
Child ; Humans ; Acyl-CoA Dehydrogenase/genetics* ; Carnitine ; Genetic Testing ; Lipid Metabolism, Inborn Errors/genetics* ; Neonatal Screening