Study on the Chain Relationship Between Self-tolerance, Self-Management, Emotional State and Cancer Bone Metastasis Pain.

Objective: To explore the interrelations among self-tolerance, self-management, emotional states, and cancer-related bone metastatic pain and to understand how these factors collectively influence patient outcomes. Methods: We conducted a study with 160 inpatients suffering from cancer-related bone metastatic pain. The study spanned from June 2022 to June 2023. Using validated instruments, we collected comprehensive clinical data and assessed participants for self-tolerance, self-management, emotional states, and pain levels. Results: The study found no significant differences in self-tolerance, self-management, emotional state, and pain across different cancer types, genders, and stages (P > .05). Notably, self-tolerance showed a negative correlation with self-management (r = -0.51, P < .001) and a positive correlation with emotional state (r = 0.266, P = .001) and pain (r = 0.34, P < .001). The standardized path coefficient values from the chain relationship model were significant, such as the impact of emotional state on pain (0.166, P = .023) and self-management on pain (-0.291, P < .01). Conclusion: The pain of cancer bone metastases is related to self-tolerance, negative emotion, and self-management. Self-tolerance can directly affect pain and can also affect pain through the chain relationship between negative emotion and self-management. The pain of cancer bone metastases is related to self-tolerance, negative emotion, and self-management. Self-tolerance can directly affect pain and can also affect pain through the chain relationship between negative emotion and self-management.

Molecular Diagnosis of Hemophilia A and Pathogenesis of Novel F8 Variants in Shanxi, China.

The aim of this study was to perform a molecular diagnosis of hemophilia A (HA) among patients in the Shanxi Province of China. Fifty-two HA patients were tested, including IVS22 (31 samples), IVS1 (3 samples), missense (11 samples), nonsense (3 samples), and 4 cases of frameshift (2 cases of deletion, 1 case of insertion, 1 case of single-base duplication). With the exception of the single-base G duplication variant (p.Ile1213Asnfs*28), this was the hotspot variant reported by research groups at an early stage. The remaining variants were found, for the first time, in the region. The missense variants p.Cys172Ser, p.Tyr404Ser, p.Asp1903Gly, and p.Ser2284Asn, the deletion variant p.Leu2249fs*9, and the insertion variant p.Pro2319fs*97 were novel variants. The application of next-generation sequencing (NGS) molecular diagnosis enriched the variant spectrum of HA, which is greatly significant for individualized genetic counseling, clinical diagnosis, and treatment. NGS and a variety of bioinformatics prediction methods can further analyze the impact of genetic variation on protein structure or function and lay the foundation to reveal the molecular pathogenic mechanism of novel variants.

Comparison of clinical efficacy and surgical safety among three bone graft modalities in spinal tuberculosis: a network meta-analysis.

BACKGROUND: Autogenous granular bone graft (AG), autogenous massive bone graft (AM), and titanium mesh bone graft (TM) are the three commonly utilized bone implant methods for spinal tuberculosis. However, the gold standard is still controversial. Therefore, this study aimed to compare the clinical efficacy and surgical safety of three primary bone graft modalities. METHODS: For systematic literature review, several databases, including PubMed, Embase, and Web of Science, were searched up to December 2022. Stata (version 14.0) was employed for data analysis. RESULTS: Our network meta-analysis included 517 patients from 7 articles whose qualities are acceptable based on our quality assessment criteria. In direct comparison, AG was associated with a shorter operation time (MD = 73.51; CI 30.65-116.37) and a lesser blood loss (MD = 214.30; CI 7.17-421.44) than AM. TM had fewer loss of Cobb angle than AG (MD = 1.45; CI 0.13-2.76) and AM (MD = 1.21; CI 0.42-1.99). Compared with AG, TM (MD = 0.96; CI 0.06-1.87) was related to a shorter bone graft fusion time. In indirect comparison, for the clinical parameters, the rank of CRP (from best to worst) was as follows: TM (58%) > AM (27%) > AG (15%), the rank of ESR (from best to worst) was as follows: AG (61%) > AM (21%) > TM (18%), and the rank of VAS (from best to worst) was as follows: AG (65%) > TM (33%) > AM (2%). In the aspect of surgical data, what is noteworthy is that AG showed less blood loss [AG (93%) > TM (6%) > AM (1%)], operative time [AG (97%) > TM (3%) > AM (0)], and complications [AG (75%) > TM (21%) > AM (4%)] than AM and TM. As for imaging parameters, the rank of the loss of Cobb angle (from best to worst) was as follows: TM (99%) > AM (1%) > AG (0). Moreover, TM showed a shorter bone graft fusion time than AM and AG: TM (96%) > AM (3%) > AG (1%). CONCLUSIONS: The results indicated that AG might be the optional treatment for spinal tuberculosis owing to the outcomes of surgical safety. Moreover, TM is another right choice which can significantly reduce the loss of Cobb angle and shorten bone graft fusion time with long-term follow-up.

[Correlation Analysis of Fâ §Gene Mutation and the Production of Fâ § Inhibitor with Severe Hemophilia A Patients in a Single Medical Center].

OBJECTIVE: To investigate the relationship between the type of FⅧgene mutation and the development of FⅧ inhibitors in patients with severe haemophilia A (HA). METHODS: The medical records of 172 patients with severe hemophilia A from January 2009 to September 2020 were reviewed. The types of FⅧgene mutations and the production of factor Ⅷ inhibitors were collected and divided into high-risk mutation group ( intron 1 inversions, large deletions, nonsense mutations), low-risk mutation group (missense mutations, small deletions and insertions, splice site mutations) and intron 22 inversions group. The correlation of FⅧgenotype and the production of FⅧ inhibitors in patients with HA were analyzed. RESULTS: Among 172 patients with severe HA, 21 cases(12.21%) developed FⅧ inhibitors. The cumulative incidence of FⅧ inhibitor development was 32%(10/31) in high risk group (75% patients with large deletions, 43% patients with intron 1 inversions, 20% patients with nonsense mutations) and 5%(2/43) in low risk group(6% patients with missense mutations, 5% patients with small deletions or insertions and 0% patient with a splice site mutation) and 9%(9/98) in intron 22 inversions group. Compared with the risk of FⅧ inhibitor development in intron 22 inversions group, the risk of FⅧ inhibitor development in high risk group was higher (OR＝4.7, 95% CI： 1.7-13.0), the risk of FⅧ inhibitor development in low risk group was equal (OR＝0.5, 95% CI： 0.1-2.3). Compared with the risk of inhibitor development in low risk group, the risk of FⅧ inhibitor development in high risk group was higher (OR＝9.8, 95% CI： 2.0-48.7). CONCLUSION: Gene mutations of patients with severe HA in high-risk group which include intron 1 inversions, large deletions, nonsense mutations are a risk factor for FⅧ inhibitor production.

Selective Laser Melting Fabrication of Porous Ti6Al4V Scaffolds With Triply Periodic Minimal Surface Architectures: Structural Features, Cytocompatibility, and Osteogenesis.

The relationship between pore architecture and structure performance needs to be explored, as well as confirm the optimized porous structure. Because of the linear correlation between constant C and pore architecture, triply periodic minimal surface (TPMS) based porous structures could be a controllable model for the investigation of the optimized porous structure. In the present work, three types of TPMS porous scaffolds (S, D and G) combined with four constants (0.0, 0.2, 0.4 and 0.6) were designed, and built successfully via the selective laser melting (SLM) technology. The designed feature and mechanical property of porous scaffolds were investigated through mathematical method and compression test. And the manufactured samples were co-cultured with rMSCs for the compatibility study. The results indicated that the whole manufacturing procedure was good in controllability, repeatability, and accuracy. The linear correlation between the porosity of TPMS porous scaffolds and the constant C in equations was established. The different TPMS porous scaffolds possess the disparate feature in structure, mechanical property and cell compatibility. Comprehensive consideration of the structure features, mechanical property and biology performance, different TPMS structures should be applied in appropriate field. The results could guide the feasibility of apply the different TPMS architectures into the different part of orthopedic implants.

A model for predicting the overall survival of gastroenteropancreatic neuroendocrine neoplasms after surgery.

BACKGROUND: The increase in the incidence of gastroenteropancreatic neuroendocrine tumors (GEP-NENs) and refined morphological imaging techniques have led to a rise in the number of patients undergoing surgery. However, there is still a paucity of objective, clinically reliable and personalized tools to evaluate patient prognosis. MATERIALS AND METHODS: We identified patients from the Surveillance, Epidemiology, and End Results (SEER) database who underwent surgery for GEP-NEN from 1975 to 2018. The predictors associated with OS were investigated by Multivariate Cox proportional hazards (PHs) regression analysis in the primary cohort; a prognostic nomogram was then built based on the multivariate analysis results. The performance of the nomogram was assessed by Harrell's concordance index (C-index) and calibration curve and compared with the eighth edition of the American Joint Committee on Cancer (AJCC) staging system. RESULTS: A total of 45,889 patients were enrolled in our study; 32,321 were included in the primary cohort, and 13,568 were included in the validation cohort. A nomogram incorporating Age, Differentiation, M staging, and AJCC staging was subsequently built based on the multivariate analysis. The C-index (0.833 for the primary cohort and 0.845 for the validation cohort) and calibration curves indicated good discriminative ability and calibration of the nomogram. Further analysis demonstrated that the nomogram had superior discriminatory ability than the AJCC staging system (C-index= 0.706). CONCLUSION: The proposed nomogram showed excellent prediction with good calibration and discrimination, which can be used to make well-informed and individualized clinical decisions regarding the clinical management of GEP-NENs.

[Altered Splicing in Stable Cell Strains Expressing Mini-hF9 Gene with Nonsense Mutation].

OBJECTIVE: To investigate the molecular mechanism in stable cell strains expressing Mini-hF9 gene with nonsense mutation. METHODS: Mini-hF9 gene and its nonsense mutants were transfected into HeLa cells independently, and stable cell strains were obtained after G418 resistance screening and monoclonal transformation. The altered splicing and protein expression of mRNA in Mini-hF9 gene in stable cell strains were detected by using RT-PCR and Western blot. RESULTS: The wild type and nonsense mutated human coagulation factor IX stable cell strains were constructed successfully, which were named HeLa-F9-WT, HeLa-F9-M1 and HeLa-F9-M2. Only normal splicing Norm was detected in the wild-type cell strain HeLa-F9-WT; Norm and Alt-S1 splicing were detected in HeLa-F9-M1; while Norm, Alt-S1 and Alt-S2 splicing were detected in HeLa-F9-M2. CONCLUSION: The nonsense associated altered splicing (NAS) pathway, which generated alternately spliced transcripts, might be triggered in coagulation factor IX gene with nonsense mutation.

Molecular mechanism of a novel Ser362Asn mutation causing inherited FX deficiency in a Chinese family.

Factor X (FX) deficiency is an inherited autosomal recessive bleeding disorder. Here, we analyzed a proband with FX deficiency in a Chinese family. Genetic analysis revealed that the proband and his affected sister was homozygous for c.1085G>A mutation, corresponding to a Ser362Asn substitution. In vitro expression experiments showed that the FX Ser362Asn mutation led to a significant reduction in activity levels in the culture medium. This Ser to Asn substitution may change the shape of the active site. Moreover, simulations of molecular dynamics indicated that the binding energy of the FX Ser362Asn to the substrate is higher than that of wild type and the side-chain conformation of the catalytic residue His276 (His42) is changed. This impairs the conformational switch of the protein from zymogen to proteinase, thus causing the functional defect of FX protein. Our findings suggest that the Ser362Asn substitution is a pathogenic mutation that causes inherited FX deficiency.

Spectrum of Molecular Defects in 216 Chinese Families With Hemophilia A: Identification of Noninversion Mutation Hot Spots and 42 Novel Mutations.

Hemophilia A (HA) is an X-linked bleeding disorder caused by heterogeneous mutations in the factor VIII gene ( F8). Our aim is to identify the causative mutations in a large HA cohort from China. We studied 216 unrelated HA families. Molecular analyses of F8 were performed using a combination of molecular techniques, including polymerase chain reaction, direct sequencing, and multiplex ligation-dependent probe amplification. The deleterious consequences of the unreported missense mutations were evaluated using various bioinformatics approaches. Causative mutations in F8 were identified in 209 families, intron 22 inversion (Inv22) was identified in 89 severe families, and intron 1 inversion (Inv1) was positive in 5 severe families; 95 mutations were detected among 115 noninversion families, of which 42 were novel, including 29 null variations and 13 missense mutations for which causality was demonstrated via bioinformatics. Among the 53 previously reported mutations, more nonsense (5 of 9) and missense (10 of 26) mutation sites were found to occur at Arginine (Arg) sites and multiple small deletions/insertions (5 of 10) located within the poly-A runs of the B domain. The majority of these sequence variants frequently recurred in the database. The odds ratios for the likelihood of developing inhibitors significantly increased in the presence of nonsense mutation. Our F8 defect spectrum was heterogeneous. Small deletions/insertions in the poly-A runs of the B domain and nonsense and missense mutations at Arg sites were identified as mutation hot spots. Nonsense mutation increased the risk of developing inhibitors.

Hemophilia care in China: review of care for 417 hemophilia patients from 11 treatment centers in Shanxi Province.

AIMS: We analyzed the clinical features of 417 patients with hemophilia from 11 Hemophilia Treatment Centers in Shanxi Province (SP) in China. METHODS: We used data collected in the national registry of hemophilia A and hemophilia B in SP from January 2010 to December 2013. RESULTS: Ratio of hemophilia A:hemophilia B patients was 5:1, of which 48% (200/417) were severe, 31% (129/417) moderate and 21% (88/417) mild. Episodes of joint bleeding occurred in 73% (305/417) of patients. Only 4% (15/417) of patients received tertiary prophylaxis. Three percent of patients (2/72) were hepatitis B virus-Ab positive, and 7% (5/72) of patients were hepatitis C virus-Ab positive. The incidence of inhibitors was 6% (11/182). CONCLUSION: The ability to manage hemophilia in SP remains suboptimal. However, due to limited data, the evaluation and extrapolation of large hemophilia populations in SP are restricted, therefore, further studies with a large cohort are needed.

[Detection of intron 22 inversion of factor VIII gene in severe hemophilia A patients].

OBJECTIVE: To investigate the incidence of intron 22 inversion (INV22) of factor VIII (FVIII) gene in severe hemophilia A (HA) patients, clarify its pathological mechanism, and identify INV22 carrier in the female family members. METHODS: One-stage method was used to assay the FVIII activity (FVIII:C)in 126 severe HA patients with a median age of 14 years old (range: 4 months-63 years). INV22 was analyzed by long-distance polymerase chain reaction (LD-PCR) and pulsed field gel electrophoresis (PFGE), and pedigree were conducted in 3 involved HA families. RESULTS: Of all the 126 severe HA, 52 (41.3%) cases had the INV22. Four females including 3 mothers and 1 sister of probands were diagnosed as INV22 carriers among 11 suspected carrier mosaicisms from 3 INV22 positive HA families. In 8 females from one family without HA history, the patient's mother was a INV22 carrier, but her maternal grandmother, 2 maternal aunts, 2 female siblings and 1 elder female cousin were negative. CONCLUSION: LD-PCR and PFGE could be used to diagnose severe HA patients with INV22 and identify the carriers.

[Expressions of Th17 cells and interleukin 17 in patients with primary immune thrombocytopenia and their clinical significance].

The aim of this study was to detect the rate of T-helper (Th)17 cells and interleukin (IL)-17 level in peripheral blood of patients with primary immune thrombocytopenia (ITP) and to explore their clinical significance. The proportion of Th17 cells from 48 patients with ITP and 28 healthy controls was detected by flow cytometry, and the IL-17 level was evaluated by enzyme-linked immunosorbent assay (ELISA). The results showed that the percentage of Th17 cells in ITP group was (1.40 ± 1.35)%, which was significantly higher than that in healthy control group (P < 0.05), but in the glucocorticoid hormone-treated group it was significantly lower than that in treated group without glucocorticoid hormone(P < 0.05). The level of IL-17 expressed by Th17 cells in ITP patients was (19.624 ± 5.187) pg/ml, which was higher than that in the healthy control group (P < 0.05), it was lower in the glucocorticoid hormone treated group than that in treated group without glucocorticoid hormone, but there was no statistically significant difference between the glucocorticoid treated and treated group without glucocorticoid hormone (P > 0.05). It is concluded that the Th17 cells may involve in the pathogenesis of ITP, and the glucocorticoid hormone probably plays a therapeutic role through inhibiting Th17 cells.

[Screening and analysis of coagulation factor VIII inhibitor in patients with hemophilia A].

In order to detect coagulation factor VIII (FVIII) inhibitor in patients with severe hemophilia A (HA) and preliminarily study the genetic mutation in patients with inhibitor positive. Totally 58 patients with HA (FVIII: C < 1%) were enrolled. FVIII: C activity was measured by one-stage coagulation assay. FVIII inhibitor was screened by using APTT method and FVIII inhibitor in screened positive patients with HA was quantitatively analyzed by using Bethesda method. Using genomic DNA as template, 12, 14, 16 exons of FVIII in screened positive patients were amplified, and the mutations of amplified products were detected by direct sequencing. The results indicated that the FVIII inhibitor could be detected in 4 patients (6.9%) from 58 HA patients, no gene mutations in 12, 14, 16 exons of FVIII were found. It is concluded that the positive rate of FVIII inhibitor in HA patients is lower than that reported in literature. The causes of inhibitor production needs to further investigate.