Does the limb lengthening reduce the incidence of hip dislocation in patients with neurological disorders and insufficient muscle tension who undergoing hip arthroplasty?

Background: The soft-tissue tension is closely associated with postoperative hip dislocation in patients undergoing total hip arthroplasty (THA), especially for those patients with neurological disorders and insufficient muscle tension. The aim of this study is to explore the effect of limb lengthening on the incidence of complications following THA in patients with neurological disorders and insufficient muscle tension. Methods: This retrospective analysis examines individuals with neurological disorders, such as ischemic stroke and poliomyelitis, who underwent primary total hip arthroplasty (THA) at our medical center between January 2015 and April 2021. Demographic and baseline characteristics (such as age, gender, muscle strength) were obtained from medical records. The limb length, offset and the positional parameters of both acetabular and femoral component were measured on pre- and postoperative plain radiograph. The primary outcome was the occurrence of hip dislocation. The secondary outcome included the incidence of other complications and the hip function (determined by Harris score). The correlation between the occurrence of hip dislocation and limb lengthening was analyzed. Results: A total of 258 patients were finally analyzed. The hip dislocations were identified in 35 patients (overall incidence = 13.57%). The incidence of early dislocation was lower in patients whose limb-length discrepancy (LLD) was over 20 mm (incidence = 4.1% for LLD >20 mm, 12.2% for LLD 10 mm-20 mm and 17% for LLD <10 mm). The odds ratio (OR) was 0.206 and 95% confidence interval (CI) was 0.058-0.737 (compared between LLD <10 mm and LLD >20 mm). But the no difference was identified regarding on the incidence of late dislocation among patients with different LLD. Moreover, the overall incidence of other complications was elevated in patients with LLD >20 mm (incidence = 17.58% for LLD >20 mm, 11.11% for LLD 10 mm-20 mm and 3.19% for LLD <10 mm; OR = 6.464, 95% CI = 1.768-23.640). And the Harris scores, which reflected the hip function, was gradually decreased with the increasing in LLD. In terms of the relationship between the offset and dislocation rate, it was found that increased offset discrepancy was associated with decreased dislocation incidence (incidence = 4.71% for offset discrepancy >10 mm, 12.5% for offset discrepancy 5 mm-10 mm and 17.20% for offset discrepancy <5 mm; OR = 0.238, 95% CI = 0.076-0.742). Furthermore, increased offset discrepancy also bring a reduction in late dislocation. The incidences of late dislocation were 0%, 2.5% and 10.8% for offset discrepancy >10 mm, offset discrepancy 5 mm-10 mm and 17.20% for offset discrepancy respectively. Different from that of LDD, the incidences of other complications were similar among patients with different offset discrepancy. Besides, no influence of offset discrepancy on the hip function was identified in this study. Conclusion: Unfortunately, although increasing in limb length could partially reduce early dislocation postoperatively, it could not affect the incidence of late dislocation in those patients with neurological disorders and insufficient muscle tension. Moreover, over limb lengthening was associated with other postoperative complications and worse hip function. Instead, additional offset could reduce the probability of postoperative dislocation, without increasing the incidence of other complications. Therefore, femoral stem with lower cervico-diaphyseal angle (higher offset) should be recommended to patients with neurological disorders who were in high risk of postoperative dislocation. Isolated increasing in limb length should be avoided.

Detection of the novel HLA-DRB5*01:01:01:07 allele by Pacific Biosciences HiFi sequencing in a Chinese individual.

HLA-DRB5*01:01:01:07 differs from HLA-DRB5*01:01:01:01 by two nucleotide changes in intron 1 and intron 2.

The oncogenic role and regulatory mechanism of ACAA2 in human ovarian cancer.

Acetyl-CoAacyltransferase2 (ACAA2) is a key enzyme in the fatty acid oxidation pathway that catalyzes the final step of mitochondrial ß oxidation, which plays an important role in fatty acid metabolism. The expression of ACAA2 is closely related to the occurrence and malignant progression of tumors. However, the function of ACAA2 in ovarian cancer is unclear. The expression level and prognostic value of ACAA2 were analyzed by databases. Gain and loss of function were carried out to explore the function of ACAA2 in ovarian cancer. RNA-seq and bioinformatics methods were applied to illustrate the regulatory mechanism of ACAA2. ACAA2 overexpression promoted the growth, proliferation, migration, and invasion of ovarian cancer, and ACAA2 knockdown inhibited the malignant progression of ovarian cancer as well as the ability of subcutaneous tumor formation in nude mice. At the same time, we found that OGT can induce glycosylation modification of ACAA2 and regulate the karyoplasmic distribution of ACAA2. OGT plays a vital role in ovarian cancer as a function of oncogenes. In addition, through RNA-seq sequencing, we found that ACAA2 regulates the expression of DIXDC1. ACAA2 regulated the malignant progression of ovarian cancer through the WNT/ß-Catenin signaling pathway probably. ACAA2 is an oncogene in ovarian cancer and has the potential to be a target for ovarian cancer therapy.

Characterization of the novel HLA-C*06:376N allele by Pacific Biosciences HiFi sequencing in a Chinese individual.

HLA-C*06:376N differs from HLA-C*06:02:01:01 by seven nucleotide changes in exon 2, intron 2, and exon 3.

The novel HLA-C*14:02:01:33 allele identified by Pacific Biosciences HiFi sequencing in a Chinese individual.

HLA-C*14:02:01:33 differs from HLA-C*14:02:01:01 by one nucleotide substitution in intron 2.

[Genetic diversity analysis and fingerprinting of 175 Chimonanthus praecox germplasm based on SSR molecular marker].

The elucidation of resources pertaining to the Chimonanthus praecox varieties and the establishment of a fingerprint serve as crucial underpinnings for advancing scientific inquiry and industrial progress in relation to C. praecox. Employing the SSR molecular marker technology, an exploration of the genetic diversity of 175 C. praecox varieties (lines) in the Yanling region was conducted, and an analysis of the genetic diversity among these varieties was carried out using the UPDM clustering method in NTSYSpc 2.1 software. We analyzed the genetic structure of 175 germplasm using Structure v2.3.3 software based on a Bayesian model. General linear model (GLM) association was utilized to analyze traits and markers. The genetic diversity analysis revealed a mean number of alleles (Na) of 6.857, a mean expected heterozygosity (He) of 0.496 3, a mean observed heterozygosity (Ho) of 0.503 7, a mean genetic diversity index of Nei՚s of 0.494 9, and a mean Shannon information index of 0.995 8. These results suggest that the C. praecox population in Yanling exhibits a rich genetic diversity. Additionally, the population structure and the UPDM clustering were examined. In the GLM model, a total of fifteen marker loci exhibited significant (P < 0.05) association with eight phenotypic traits, with the explained phenotypic variation ranging from 14.90% to 36.03%. The construction of fingerprints for C. praecox varieties (lines) was accomplished by utilizing eleven primer pairs with the highest polymorphic information content, resulting in the analysis of 175 SSR markers. The present study offers a thorough examination of the genetic diversity and SSR molecular markers of C. praecox in Yanling, and establishes a fundamental germplasm repository of C. praecox, thereby furnishing theoretical underpinnings for the selection and cultivation of novel and superior C. praecox varieties, varietal identification, and resource preservation and exploitation.

Viral integration promotes SV40T-induced immortalization by disturbing the expression of DNA/chromosome- and ECM-associated functional genes.

Lentivirus containing simian virus 40 large T antigen (SV40T) is routinely used to induce cell immortalization. However, the roles of viral integration itself in this progress is still controversial. Here, we transformed primary mouse embryonic fibroblasts (MEFs) with SV40T lentivirus and studied the roles of viral integration in the immortalization using RNA sequencing (RNA-seq) and whole genome sequencing (WGS). During the immortalization, differentially expressed genes (DGEs) are enriched in viral infection and several diverse activities. However, DEGs between immortalized and aging cells are significantly enriched in DNA/chromosome- and extracellular matrix (ECM)-associated activities. Gene regulatory network (GRN) analysis shows that although p53 is a key regulatory factor, many other transcription factors also play critical roles in the process, like STAT1. Of these DEGs, 32 genes have viral integration in their coding and/or regulatory regions. Our findings suggest that viral integration may promote SV40T-mediated immortalization by disturbing the expression of DNA/chromosome- and ECM-associated genes.

Deep Variational Free Energy Approach to Dense Hydrogen.

We developed a deep generative model-based variational free energy approach to the equations of state of dense hydrogen. We employ a normalizing flow network to model the proton Boltzmann distribution and a fermionic neural network to model the electron wave function at given proton positions. By jointly optimizing the two neural networks we reached a comparable variational free energy to the previous coupled electron-ion Monte Carlo calculation. The predicted equation of state of dense hydrogen under planetary conditions is denser than the findings of ab initio molecular dynamics calculation and empirical chemical model. Moreover, direct access to the entropy and free energy of dense hydrogen opens new opportunities in planetary modeling and high-pressure physics research.

Degradation of 2,4-DCP by immobilized laccase on modified biochar carrier.

Rape straw was used as the raw material for the biochar in this study, which was then changed using acid, alkali, and magnetic techniques. The laccase was attached using the adsorptions-crosslinking process, and the three modified biochars served as the carriers. The ideal circumstances for laccase immobilization were explored, and both biochar and immobilized laccase's characteristics were examined. The removal of 2,4-dichlorophenol (2,4-DCP) by immobilized laccase from modified biochar and its degradation products were researched. The main conclusions are as follows: the optimal concentration of glutaraldehyde (GLU) was 4%, and the pH was four, and the enzyme dosage was 1.75 mg/mL for the immobilized laccase of acid-modified biochar (SBC@LAC). The optimal concentration of GLU was 5%; the pH was four, and the enzyme dosage was 2 mg/mL for immobilized laccase from alkali-modified biochar (JBC@LAC). The optimal concentration of GLU was 5%; the pH was four, and the enzyme dosage was 1.75 mg/mL for immobilized laccase from magnetically modified biochar (CBC@LAC). SEM images could show the changes in the surface morphology of biochar caused by three modification methods. The BET results demonstrated that acid and magnetic modification increased the specific surface area of biochar, and alkali modification mainly expanded the pore size of biochar. FT-IR and XRD showed that modification and laccase loading had little effect on the structure of biochar. The stability of immobilized laccase was better than that of free laccase in acid-base, heat, and storage. Among the three modified biochar immobilized laccases, JBC@LAC showed the best acid-base stability and thermal stability, and the relative enzyme activity changed the least when pH and temperature conditions changed. The storage stability of SBC@LAC is the best. After 30 days of storage, the relative enzyme activity is still 83%. The removal rates of 2,4-DCP were 57, 99, and 63%, respectively, by SBC@LAC, JBC@LAC, and CBC@LAC. After five reuses, the removal rates of 2,4-DCP by SBC@LAC, JBC@LAC and CBC@LAC were 26, 42, and 27%, respectively. The intermediate products of 2,4-DCP degradation by immobilized laccase were p-phenol, p-benzoquinone and maleic acid.

ApoE4 exacerbates the senescence of hippocampal neurons and spatial cognitive impairment by downregulating acetyl-CoA level.

Although aging and apolipoprotein E (APOE) ε4 allele have been documented as two major risk factors for late-onset Alzheimer's disease (LOAD), their interaction and potential underlying mechanisms remain unelucidated. Using humanized ApoE4- and ApoE3- target replacement mice, we found the accumulation of senescent neurons and the activation of mTOR and endosome-lysosome-autophagy (ELA) system in the hippocampus of aged ApoE4 mice. Further analyses revealed that ApoE4 aggravated the profile change of hippocampal transcription and metabolism in an age-dependent manner, accompanying with an disruption of metabolism, which is presented with the downregulating activity of citrate synthase, the level of ATP and, most importantly, the level of acetyl coenzyme A (Ac-CoA); GTA supplement, an Ac-CoA substrate, reversed the senescent characteristics, decreased the activation of mTOR and ELA system, and enhanced the synaptic structure and increasing level of pre-/post-synaptic plasticity-related protein, leading to cognitive improvement in aged ApoE4 mice. These data suggest that ApoE4 exacerbates neuronal senescence due to a deficiency of acetyl-CoA, which can be ameliorated by GTA supplement. The findings provide novel insights into the potential therapeutic value of GTA supplement for the cognitive improvement in aged APOE4 carriers.

[Genetic diversity analysis and fingerprints of Chrysanthemum×morifolium based on SSR molecular markers].

The present study aims to explore the genetic diversity of germplasm resources of Chrysanthemum×morifolium (hereinafter, C.×morifolium) at the molecular level and to establish a fingerprint database of C.×morifolium varieties. We employed 12 pairs of primers with high levels of polymorphism, clear bands, and high degrees of reproducibility to analyze the SSR molecular markers and genetic diversity of 91 C.×morifolium materials and 14 chrysanthemum- related materials. With regard to constructing the fingerprints of the tested materials, we chose 9 pairs of core primers. The findings revealed that 12 primer pairs detected 104 alleles in 105 samples, ranging from 2 to 26. The average number of observed alleles (Na) per site was 9.25. The average number of effective alleles (Ne) per site was 2.745 6, with its range being 1.276 0 to 4.742 5. Shannon genetic diversity index (I) values ranged between 0.513 3 and 2.239 9 (M=1.209 0). Nei's gene diversity index (H) ranged between 0.216 3 and 0.789 1 (M=0.578 0). The observed heterozygosity (Ho) ranged between 0.223 3 and 0.895 2 (M=0.557 5). The expected heterozygosity (He) ranged between 0.217 4 and 0.793 3 (M=0.580 8). The polymorphism information content (PIC) ranged between 0.211 5 and 0.774 0 (M=0.532 9). The genetic similarity (GS) ranged between 0.228 5 and 1.000 0 (M=0.608 3). Cluster analysis revealed that when the genetic distance (GD) equals to 0.30, the tested materials can be classified into 2 groups. When the GD equals to 0.27, the first group can be divided into 6 subgroups; accordingly, 105 tested materials can be divided into 7 subgroups. The cophenetic correlation test was carried out based on the cluster analysis, and the corresponding results showed that the cluster map correlated with the genetic similarity coefficient (r=0.952 73). According to the results of Structure population analysis, we obtained the optimal population number, with the true number of populations (K) being 3 and the population being divided concerning Q≥0.5. Three subgroups, i.e., Q1, Q2 and Q3, included 34, 33 and 28 germplasms, respectively, and the remaining 10 germplasms were identified as the mixed population. During the experiment, 9 pairs of core primers were screened among the total of 12 for a complete differentiation regarding 105 tested materials, and the fingerprints of 91 C.×morifolium materials and 14 chrysanthemum-related materials were further constructed. Overall, there were significant genetic differences and rich genetic diversity among C.×morifolium materials, which would shed light on the garden application and variety selection fields of C.×morifolium. The fingerprint database of 105 C.×morifolium varieties and chrysanthemum-related species may provide technical support for future research regarding the identification and screening system of C.×morifolium varieties.

LncRNA GAS5-hnRNPK axis inhibited ovarian cancer progression via inhibition of AKT signaling in ovarian cancer cells.

BACKGROUND: The incidence of ovarian cancer ranks third among gynecologic malignancies, but the mortality rate ranks first. METHODS: The expression of GAS5 is low in ovarian cancer and is associated with the low survival of ovarian cancer patients according to public ovarian cancer databases. GAS5 overexpression inhibited ovarian malignancy by affecting the proliferation and migratory abilities in OVCAR3 and A2780 cells. GAS5 overexpression increased the rate of cell apoptosis, and the cells were blocked in the G1 phase as assessed by flow cytometry. RESULTS: We found that hnRNPK was a potential target gene, which was regulated negatively by GAS5 based on RNA-pulldown and mass spectrometry analysis. Mechanistically, GAS5 affected the inhibition of the PI3K/AKT/mTOR pathways and bound the protein of hnRNPK, which influenced hnRNPK stability. Furthermore, rescue assays demonstrated hnRNPK was significantly involved in the progression of ovarian cancer. CONCLUSIONS: Our study showed one of the mechanisms that GAS5 inhibited ovarian cancer metastasis by down-regulating hnRNPK expression, and GAS5 can be used to predict the prognosis of ovarian cancer patients.

Effectiveness of Needle Aspiration versus Surgical Excision for Symptomatic Synovial Cysts of the Hip: A Single-Center, Retrospective Study.

BACKGROUND This study was performed to evaluate the clinical effectiveness of needle aspiration vs surgical excision for symptomatic synovial cysts of the hip. MATERIAL AND METHODS This retrospective study analyzed the clinical data of patients diagnosed with synovial cysts of the hip and treated in a single-center hospital from January 2012 to April 2022. Patients receiving needle aspiration were assigned to group A and those treated with surgery were assigned to group B. Demographic characteristics, etiology, symptoms, cyst location, postoperative complications and recurrence, Harris Hip Score (HHS) and Visual Analog Scale of Pain (VAS) scores before treatment and at 3, 6, and 12 months after treatment were recorded to assess hip function in both groups. RESULTS This study recruited 44 patients, with 18 patients in group A and 26 in group B, and the 2 arms were well-balanced in terms of baseline patient profiles. Needle aspiration resulted in significantly better pain mitigation for patients at 24 h, 48 h, and 72 h after treatment vs surgical interventions (P<0.05). Needle joint aspiration resulted in significantly better function restoration of the hip joint than surgery at 3 months after treatment, as evidenced by the lower HHS score of 85.31±13.16 in group A vs 78.51±11.66 in group B (P=0.002). Surgery was associated with a significantly lower incidence of disease relapse (0.00%) vs needle aspiration (27.7%) (P=0.004). CONCLUSIONS Needle aspiration in the treatment of symptomatic synovial cysts of the hip causes less damage to the soft tissue and leads to faster recovery in the short term than surgical resection. Surgical resection has a lower recurrence rate and better long-term efficacy.

Structural basis of gRNA stabilization and mRNA recognition in trypanosomal RNA editing.

In Trypanosoma brucei, the editosome, composed of RNA-editing substrate-binding complex (RESC) and RNA-editing catalytic complex (RECC), orchestrates guide RNA (gRNA)-programmed editing to recode cryptic mitochondrial transcripts into messenger RNAs (mRNAs). The mechanism of information transfer from gRNA to mRNA is unclear owing to a lack of high-resolution structures for these complexes. With cryo-electron microscopy and functional studies, we have captured gRNA-stabilizing RESC-A and gRNA-mRNA-binding RESC-B and RESC-C particles. RESC-A sequesters gRNA termini, thus promoting hairpin formation and blocking mRNA access. The conversion of RESC-A into RESC-B or -C unfolds gRNA and allows mRNA selection. The ensuing gRNA-mRNA duplex protrudes from RESC-B, likely exposing editing sites to RECC-catalyzed cleavage, uridine insertion or deletion, and ligation. Our work reveals a remodeling event facilitating gRNA-mRNA hybridization and assembly of a macromolecular substrate for the editosome's catalytic modality.

Prediction of miRNA-disease associations in microbes based on graph convolutional networks and autoencoders.

MicroRNAs (miRNAs) are short RNA molecular fragments that regulate gene expression by targeting and inhibiting the expression of specific RNAs. Due to the fact that microRNAs affect many diseases in microbial ecology, it is necessary to predict microRNAs' association with diseases at the microbial level. To this end, we propose a novel model, termed as GCNA-MDA, where dual-autoencoder and graph convolutional network (GCN) are integrated to predict miRNA-disease association. The proposed method leverages autoencoders to extract robust representations of miRNAs and diseases and meantime exploits GCN to capture the topological information of miRNA-disease networks. To alleviate the impact of insufficient information for the original data, the association similarity and feature similarity data are combined to calculate a more complete initial basic vector of nodes. The experimental results on the benchmark datasets demonstrate that compared with the existing representative methods, the proposed method has achieved the superior performance and its precision reaches up to 0.8982. These results demonstrate that the proposed method can serve as a tool for exploring miRNA-disease associations in microbial environments.

Tri-Lock Bone Preservation Stem Versus Conventional Corail Stem in Primary Total Hip Arthroplasty via Direct Anterior Approach: A Short-Term, Retrospective, Comparative Study.

BACKGROUND he present study was performed to evaluate the clinical efficacy of Tri-Lock bone preservation stems vs conventional Corail stems in primary total hip arthroplasty via direct anterior approach. MATERIAL AND METHODS In this retrospective analysis, patients receiving THA via DAA in a single-center hospital from January 2019 to March 2020 were assessed for eligibility and assigned to either a Tri-Lock BPS group or a Corail group based on the use of prostheses. Outcome measures for the efficiency evaluation of the 2 prostheses included perioperative outcomes, imaging results, Harris Hip Score, Western Ontario and McMaster University Osteoarthritis Index, and visual analog scale scores at 3, 6, 12, and 24 months postoperatively. RESULTS A total of 204 patients were included, including 98 patients (98 hips) in the Tri-Lock BPS group and 106 patients (106 hips) in the Corail group. Patients receiving Tri-Lock BPS exhibited better pain relief than those with Coral stems. Tri-Lock BPS had a higher safety profile vs Corail stems by significantly reducing the risk of complications (P=0.004). A markedly increased HHS score (84.42±16.27 vs 78.61±12.78, P=0.002) and a lower WOMAC score (25.08±15.39 vs 32.14±11.56, P=0.001) at 3 months postoperatively were observed in patients with Tri-Lock BPS vs those with Corail stems, indicating better restoration of hip function using Tri-Lock BPS. CONCLUSIONS During total hip arthroplasty via DAA, Tri-Lock BPS causes a smaller surgical wound, reduces the operative time and intraoperative bleeding, and produces less soft-tissue damage vs Corail stems, providing great benefits in femoral prosthesis placement.

Efficacy of Direct Anterior Approach Versus Posterior Lateral Approach for Total Hip Replacement in Patients with Parkinson's Disease.

BACKGROUND The present study was performed to evaluate the efficacy of direct anterior approach (DAA) versus posterolateral approach (PLA) for total hip arthroplasty (THA) in patients with Parkinson's disease (PD). The aim of the study was to compare the speed of recovery of hip function and postoperative complications between the 2 approaches. MATERIAL AND METHODS The study included 285 Parkinson's patients who underwent THA; 209 eligible patients were recruited for analysis as per the inclusion criteria and assigned into DAA group (n=90) and PLA group (n=119) according to the surgical approach. Postoperative Harris Hip Score (HHS), Western Ontario and McMaster University Osteoarthritis Index (WOMAC), and Forgotten joint score (FJS) were collected to assess hip function. RESULTS The DAA had a statistically lower incidence of postoperative complications than the PLA, particularly the rate of postoperative dislocation. Perioperative outcomes showed a longer operative time in the DAA than in the PLA group and more intraoperative blood loss in the DAA than in the PLA group. At 3 months postoperatively, the HHS and WOMAC scores in the DAA group showed significantly higher scores compared to the PLA group versus the DAA group. However, these differences disappeared at 6 months postoperatively and the FJS in the DAA group had a statistically higher score compared to the PLA group. CONCLUSIONS In patients with Parkinson's disease complicated with hip disease, the DAA approach exhibited a lower rate of dislocation than the PLA approach and had faster recovery of hip function.

Comparison of Outcomes Following Total Hip Arthroplasty Between Patients Diagnosed with Association Research Circulation Osseous (ARCO) Stage III and Stage IV Osteonecrosis of the Femoral Head: A Retrospective Study of 302 Patients.

BACKGROUND This retrospective study from a single center aimed to compare outcomes following total hip arthroplasty (THA) in 302 patients diagnosed with Association Research Circulation Osseous (ARCO) stage III and stage IV osteonecrosis of the femoral head (ONFH). MATERIAL AND METHODS The study included 302 patients who underwent THA for ONFH between January 2018 and September 2021. Patient groups included ARCO stage III (n=145) and ARCO stage IV (n=157). Outcomes measured included duration of disease, operative time, intraoperative blood volume, postoperative length of hospital stay, pain measured by the visual analog scale (VAS) score, Harris hip score (HHS), and forgotten joint score (FJS). RESULTS Patients with ARCO stage III ONFH had a significantly shorter operative time (P=0.009), shorter length of hospital stay (P=0.021), and reduced volume of intraoperative bleeding (P=0.021) compared with patients with ARCO stage IV ONFH. There were no significant differences in disease duration (P=0.310), postoperative complications (P=0.07), preoperative (P=0.086, P=0.156) and postoperative (P=0.062, P=0.173) HHS and VAS scores, respectively. Patients with stage III ONFH reported significantly higher FJS scores at 3 months, 6 months, and 1 year after THA. CONCLUSIONS Patients who underwent hip arthroplasty for ARCO stage III femoral head necrosis experienced shorter operative time and hospital stay, less intraoperative bleeding, and better restoration of hip function than those with ARCO stage IV. Moreover, stage III patients were more prone to "forget" their hip arthroplasty experience within 1 year of surgery.

Analysis of the current status and influencing factors of cross-regional hospitalization services utilization by basic medical insurance participants in China - taking a central province as an example.

Background: The geographically uneven distribution of healthcare resources has resulted in a dramatic increase of cross-regional hospitalization services in China. The over-use of cross-regional hospitalization services may hinder the utilization and improvement of local hospitalization services. It is of great practical significance to study the utilization of cross-regional hospitalization services and its influencing factors in order to effectively allocate medical resources and guide patients to seek medical treatment rationally. Therefore, this study aims to analyze the current situation and influencing factors of the utilization of cross-regional hospitalization services by patients insured by basic medical insurance in China. Methods: A total of 3,291 cross-provincial inpatients were randomly selected in a central province of China in 2020. The level of medical institutions, hospitalization expenses and actual reimbursement rate were selected as indicators of hospitalization service utilization. Exploratory factor analysis was used to assess the dimensionality of influencing factors and reduce the number of variables, and binomial logistic regression analysis and multiple linear regression analysis to explore the influencing factors of the utilization of cross-regional hospitalization services. Results: The proportion of cross-provincial inpatients choosing tertiary hospitals was the highest with average hospitalization expenses of 24,662 yuan and an actual reimbursement rate of 51.0% on average. Patients insured by Urban Employees' Basic Medical Insurance (UEBMI) were more frequently (92.9% vs. 88.5%) to choose tertiary hospitals than those insured by Urban and Rural Residents' Basic Medical Insurance (URRBMI), and their average hospitalization expenses (30,727 yuan) and actual reimbursement rate (68.2%) were relatively higher (p < 0.001). The factor "income and security," "convenience of medical treatment" and "disease severity" had significant effects on inpatients' selection of medical institution level, hospitalization expenses and actual reimbursement rate, while the factor "demographic characteristics" only had significant effects on hospitalization expenses and actual reimbursement rate. Conclusion: Cross-provincial inpatients choose tertiary hospitals more frequently, and their financial burdens of medical treatment are heavy. A variety of factors jointly affect the utilization of cross-provincial hospitalization services for insured patients. It is necessary to narrow down the gap of medical treatment between UEBMI and URRBMI patients, and make full use of high-quality medical resources across regions.

Integrating cell interaction with transcription factors to obtain a robust gene panel for prognostic prediction and therapies in cholangiocarcinoma.

Objective: The efficacy of immunotherapy for cholangiocarcinoma (CCA) is blocked by a high degree of tumor heterogeneity. Cell communication contributes to heterogeneity in the tumor microenvironment. This study aimed to explore critical cell signaling and biomarkers induced via cell communication during immune exhaustion in CCA. Methods: We constructed empirical Bayes and Markov random field models eLBP to determine transcription factors, interacting genes, and associated signaling pathways involved in cell-cell communication using single-cell RNAseq data. We then analyzed the mechanism of immune exhaustion during CCA progression. Results: We found that VEGFA-positive macrophages with high levels of LGALS9 could interact with HAVCR2 to promote the exhaustion of CD8+ T cells in CCA. Transcription factors SPI1 and IRF1 can upregulate the expression of LGALS9 in VEGFA-positive macrophages. Subsequently, we obtained a panel containing 54 genes through the model, which identified subtype S2 with high expression of immune checkpoint genes that are suitable for immunotherapy. Moreover, we found that patients with subtype S2 with a higher mutation ratio of MUC16 had immune-exhausted genes, such as HAVCR2 and TIGIT. Finally, we constructed a nine-gene eLBP-LASSO-COX risk model, which was designated the tumor microenvironment risk score (TMRS). Conclusion: Cell communication-related genes can be used as important markers for predicting patient prognosis and immunotherapy responses. The TMRS panel is a reliable tool for prognostic prediction and chemotherapeutic decision-making in CCA.