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Abstract Background This work aimed to investigate the change in fingerprint depth and the recovery rule of fingerprint biological recognition function after repairing finger abdominal defects and rebuilding fingerprint with a free flap. Method From April 2018 to March 2023, we collected a total of 43 cases of repairing finger pulp defects using the free flap of the fibular side of the great toe with the digital nerve. After surgery, irregular follow-up visits were conducted to observe fingerprint clarity, perform the ninhydrin test or detect visible sweating with the naked eye. We recorded fingerprint clarity, nail shape, two-point discrimination, cold perception, warm perception and fingerprint recognition using smartphones. The reconstruction process of the repaired finger was recorded to understand the changes in various observation indicators and their relationship with the depth of the fingerprint. The correlation between fingerprint depth and neural repair was determined, and the process of fingerprint biological recognition function repair was elucidated. Result All flaps survived, and we observed various manifestations in different stages of nerve recovery. The reconstructed fingerprint had a clear fuzzy process, and the depth changes of the fingerprint were consistent with the changes in the biological recognition function curve. Conclusion The free flap with the digital nerve is used to repair finger pulp defects. The reconstructed fingerprint has a biological recognition function, and the depth of the fingerprint is correlated with the process of nerve repair. The fingerprint morphology has a dynamic recovery process, and it can reach a stable state after 6–8 months.

Abstract Background Human toxocariasis is a neglected parasitic disease characterised by the syndromes visceral, cerebral, and ocular larva migrans. This disease is caused by the migrating larvae of Toxocara roundworms from dogs and cats, affecting 1.4 billion people globally. Via extracellular vesicles (EVs), microRNAs have been demonstrated to play roles in host–parasite interactions and proposed as circulating biomarkers for the diagnosis and follow-up of parasitic diseases. Methods Small RNA-seq was conducted to identify miRNAs in the infective larvae of T. canis and plasma EV-containing preparations of infected BALB/c mice. Differential expression analysis and target prediction were performed to indicate miRNAs involved in host–parasite interactions and miRNAs associated with visceral and/or cerebral larva migrans in the infected mice. Quantitative real-time polymerase chain reaction (PCR) was used to amplify circulating miRNAs from the infected mice. Results This study reports host and parasite miRNAs in the plasma of BALB/c mice with visceral and cerebral larva migrans and demonstrates the alterations of these miRNAs during the migration of larvae from the livers through the lungs and to the brains of infected mice. After filtering unspecific changes in an irrelevant control, T. canis-derived miRNAs and T. canis infection-induced differential miRNAs are predicted to modulate genes consistently involved in mitogen-activated protein kinase (MAPK) signalling and pathways regulating axon guidance and pluripotency of stem in the infected mice with visceral and cerebral larva migrans. For these plasma circulating miRNAs predicted to be involved in host-parasite crosstalk, two murine miRNAs (miR-26b-5p and miR-122-5p) are experimentally verified to be responsive to larva migrans and represent circulating biomarker candidates for visceral and cerebral toxocariasis in BALB/c mice. Conclusions Our findings provide novel insights into the crosstalk of T. canis and the mammalian host via plasma circulating miRNAs, and prime agents and indicators for visceral and cerebral larva migrans. A deep understanding of these aspects will underpin the diagnosis and control of toxocariasis in humans and animals. Graphical Abstract

ObjectiveTo investigate the epidemiological characteristics of hypothyroidism in Qinghai Province, analyze its related influencing factors, establish the normal reference range of thyroid function, and explore the relationship between thyroid hormone (THs), thyroid stimulating hormone (TSH) and metabolic syndrome (MS) in Qinghai population within the normal range, so as to provide some scientific basis for the prevention and treatment of hypothyroidism in Qinghai Province.MethodsA total of 2790 residents aged 18 and over from Qinghai were selected through stratified cluster random sampling. Data were collected via questionnaires, physical examinations, and laboratory tests.Results1. A total of 2628 eligible residents in Qinghai were included in this study, and the total prevalence of hypothyroidism was 30.25%, among which the prevalence of subclinical hypothyroidism was 29.22%, and the prevalence of clinical hypothyroidism was 1.03%. 2. The prevalence of hypothyroidism in women was significantly higher than that in men (36.69% vs 24.30%); smoking and drinking were risk factors for hypothyroidism. 3. In the excluded subjects, 1544 were abnormal thyroid ultrasound, abnormal thyroid function and/or positive thyroid autoantibodies, and the remaining 1084 were reference populations. According to the reference population data, the 95% reference ranges of TSH, FT4, FT3 were 0.43-5.51 mIU/L, 11.0-20.4 pmol/L, 3.63-5.73 pmol/L, respectively. 4. In the normal thyroid function population in Qinghai, MS and its related components were positively correlated with FT3 and FT4 levels, but not significantly correlated with TSH levels.Conclusion1. The prevalence of hypothyroidism in adults in Qinghai is relatively high, accounting for about one-thirtieth of the total population. Smoking and drinking have a certain impact on the incidence of hypothyroidism. 2. It provides a reference range for the diagnosis of thyroid diseases in Qinghai province, which is different from that of reagent suppliers, and has certain promotion significance in the western region. 3. MS and its related components are positively correlated with FT3 and FT4 levels, but not with TSH levels in people with normal thyroid function in Qinghai. Early thyroid function screening is of great significance for the prevention of MS.

Abstract Protein-encoding genes only constitute less than 2% of total human genomic sequences, and 98% of genetic information was previously referred to as “junk DNA”. Meanwhile, non-coding RNAs (ncRNAs) consist of approximately 60% of the transcriptional output of human cells. Thousands of ncRNAs have been identified in recent decades, and their essential roles in the regulation of gene expression in diverse cellular pathways associated with fundamental cell processes, including proliferation, differentiation, apoptosis, and metabolism, have been extensively investigated. Furthermore, the gene regulation networks they form modulate gene expression in normal development and under pathological conditions. In this review, we integrate current information about the classification, biogenesis, and function of ncRNAs and how these ncRNAs support skeletal development through their regulation of critical genes and signaling pathways in vivo. We also summarize the updated knowledge of ncRNAs involved in common skeletal diseases and disorders, including but not limited to osteoporosis, osteoarthritis, rheumatoid arthritis, scoliosis, and intervertebral disc degeneration, by highlighting their roles established from in vivo, in vitro, and ex vivo studies.

Abstract Total knee arthroplasty (TKA) is the most cost-effective, and potent method for the treatment of end-stage knee osteoarthritis. Acute normovolemic haemodilution (ANH) can effectively replace the need for allogeneic transfusions due to the high amount of bleeding during TKA. However, more studies are needed to prove the efficacy and safety of ANH and to clarify its indications in the field of knee replacement. Medical records from June 1, 2019 to June 1, 2021 were searched and grouped according to inclusion and exclusion criteria. PART I: 58 patients with ANH during TKA were selected as the ANH group (n = 58), and 58 patients with allogeneic transfusion were chosen as the control group (n = 58). PART II: Patients with anaemia were divided into the ANH group (n = 18) and the control group (n = 12). PART I: The postoperative inflammatory index and serum albumin in the ANH group were significantly lower than those in the control group. No significant difference was observed in the theoretical loss of red blood cells, postoperative renal function, liver function, cardiac function and biochemical ion index between the two groups. The effective rate of ANH in the normal haemoglobin group was significantly lower than that in the anaemia group. PART II: In patients with anaemia, the theoretical loss of red blood cells in patients with ANH was less than that in the control group. The postoperative inflammation, renal function, liver function and cardiac function in the ANH group were better than those in the control group, and no significant difference was noted in biochemical ions and nutritional status indicators. This paper shows that ANH not only can replace allogeneic transfusion in TKA, especially in patients with anaemia, but also has lower inflammatory indicators than allogeneic transfusion. From a security perspective, the body’s tolerance to ANH is within the body’s compensation range.

Abstract Background Osteosarcoma (OS) is the most common primary malignant bone tumor in children and adolescents, with poor outcomes for patients with metastatic disease or chemotherapy resistance. Cirsiliol is a recently found flavonoid with anti-tumor effects in various tumors. However, the effects of cirsiliol in the regulation of aggressive behaviors of OS remain unknown. Methods The effect of cirsiliol on the proliferation of OS cells was detected using a cell counting kit-8 (CCK-8) assay and 5-ethynyl-2′-deoxyuridine (EdU) staining, while cell apoptosis was detected using flow cytometry. Immunofluorescence was applied to visualize the expression level of the mitochondria, lysosomes and microtubule-associated protein light chain 3 (LC3). A computational molecular docking technique was used to predict the interaction between cirsiliol and the AKT protein. The impact of cirsiliol on resistance was investigated by comparing it between a methotrexate (MTX)-sensitive OS cell line, U2OS, and a MTX-resistant OS cell line, U2OS/MTX. Finally, in situ xenogeneic tumor models were used to validate the anti-tumor effect of cirsiliol in OS. Results Cirsiliol inhibited cell proliferation and induced apoptosis in both U2OS and U2OS/MTX300 OS cells. In addition, treatment with cirsiliol resulted in G2 phase arrest in U2OS/MTX300 and U2OS cells. Cell fluorescence probe staining results showed impaired mitochondria and increased autophagy in OS cells after treatment with cirsiliol. Mechanistically, it was found that cirsiliol targeted AKT by reducing the phosphorylation of AKT, which further activated the transcriptional activity of forkhead Box O transcription factor 1 (FOXO1), ultimately affecting the function of OS cells. Moreover, in situ tumorigenesis experiments showed that cirsiliol inhibited the tumorigenesis and progression of OS in vivo. Conclusions Cirsiliol inhibits OS cell growth and induces cell apoptosis by reducing AKT phosphorylation and further promotes FOXO1 expression. These phenomena indicate that cirsiliol is a promising treatment option for OS.

Background: Implantation failure, especially recurrent implantation failure (RIF), causes considerable distress in patients who undergo assisted reproductive techniques (ART). Mild pathologies inside the uterine cavity and disturbance of the uterine environment can decrease endometrial receptivity and cause implantation failure. To address this, hysteroscopy combined with endometrial pathological diagnosis has become more widespread. However, the specific time at which to perform the hysteroscopy remains controversial in the clinical practice of ART. Methods: This case-control studies enrolled a total of 1876 in-vitro fertilization embryo transfer (IVF-ET) or intracytoplasmic sperm injection embryo transfer (ICSI-ET) patients with a history of failed implantation were included in this study. From October 2019 to December 2022, these patients underwent office hysteroscopy and subsequent endometrial biopsy for CD138 immunohistochemistry to detect chronic endometritis (CE) in the Department of Reproductive Medicine, West China Second University Hospital, Sichuan University. Endometrial polys (EP) were removed during surgery, and for patients diagnosed with CE, oral doxycycline was taken for two consecutive weeks before the next frozen embryo transfer (FET). Patient demographic characteristics and pregnancy outcomes were reviewed and analyzed by logistic regression to evaluate outcomes. Results: Patients were divided into four groups according to hysteroscopy findings and pathological diagnosis: CE only, CE plus EP, EP only, and neither CE or EP. The biochemical pregnancy (p = 0.009), clinical pregnancy (p = 0.014), and live birth (p = 0.011) rates after the following FET cycle were significantly different between the four groups. Pregnancy outcomes for the CE plus EP group were better than for the other three groups. Multivariate logistic regression analysis revealed that the probability of live birth was significantly related to the mother’s age, the controlled ovarian stimulation (COS) protocol, the number of times with failed embryo transfer (ET) cycle, endometrial histology findings, the interval time between hysteroscopy and FET, the endometrial thickness on the day of embryo transfer, and the number and type of embryos transferred (p < 0.05). Conclusions: Office hysteroscopy combined with diagnosis of endometrial pathology is a valuable approach for women with a history of implantation failure. This approach is not limited to RIF patients, and results in an increased pregnancy rate and shorter time to live birth in ART.

Abstract Objective This study aims to demonstrate the cellular composition and underlying mechanisms in subchondral bone marrow lesions (BMLs) of knee osteoarthritis (OA). Methods BMLs were assessed by MRI Osteoarthritis Knee Score (MOAKS)≥2. Bulk RNA-sequencing (bulk-seq) and BML-specific differentially expressed genes (DEGs) analysis were performed among subchondral bone samples (including OA-BML=3, paired OA-NBML=3; non-OA=3). The hub genes of BMLs were identified by verifying in independent datasets and multiple bioinformatic analyses. To further estimate cell-type composition of subchondral bone, we utilized two newly developed deconvolution algorithms (MuSiC, MCP-counter) in transcriptomic datasets, based on signatures from open-accessed single-cell RNA sequencing (scRNA-seq). Finally, competing endogenous RNA (ceRNA) and transcription factor (TF) networks were constructed through multiple predictive databases, and validated by public non-coding RNA profiles. Results A total of 86 BML-specific DEGs (up 79, down 7) were identified. IL11 and VCAN were identified as core hub genes. The “has-miR-424-5p/lncRNA PVT1” was determined as crucial network, targeting IL11 and VCAN, respectively. More importantly, two deconvolution algorithms produced approximate estimations of cell-type composition, and the cluster of heterotopic-chondrocyte was discovered abundant in BMLs, and positively correlated with the expression of hub genes. Conclusion IL11 and VCAN were identified as the core hub genes of BMLs, and their molecular networks were determined as well. We profiled the characteristics of subchondral bone at single-cell level and determined that the heterotopic-chondrocyte was abundant in BMLs and was closely linked to IL11 and VCAN. Our study may provide new insights into the microenvironment and pathological molecular mechanism of BMLs, and could lead to novel therapeutic strategies.

Abstract Background This study aims to (1) identify preoperative testing-based characteristics associated with enhanced prognosis and survival for cholangiocarcinoma patients, and (2)create a distinctive nomogram to anticipate each patient’s cancer-specific survival (CSS). Methods Retrospective analysis was performed on 197 CCA patients who underwent radical surgery at Sun Yat-sen Memorial Hospital; they were divided into a 131-person “training cohort” and a 66-person “internal validation cohort.“ The prognostic nomogram was created following a preliminary Cox proportional hazard regression search for independent factors influencing the patients’ CSS. Its applicable domain was examined via an external validation cohort, which included 235 patients from the Sun Yat-sen University Cancer Center. Results The median follow-up period for the 131 patients in the training group was 49.3 months (range, 9.3 to 133.9 months). One-, three-, and five-year CSS rates were 68.7%, 24.5%, and 9.2%, respectively, with the median CSS length being 27.4 months (range: 1.4 to 125.2 months). PLT, CEA, AFP, tumor location, differentiation, lymph node metastasis, chemotherapy, and TNM stage were determined to be independent risk factors for CCA patients by univariate and multivariate Cox proportional hazard regression analysis. We were able to accurately predict postoperative CSS after incorporating all of these characteristics into a nomogram. The AJCC’s 8th edition staging method’s C-indices were statistically substantially (P

The key to whether elderly individuals in the community can enjoy their later years peacefully lies in the service capabilities of community comprehensive elderly care service facilities (CCECSF) under the Public-Private Partnership (PPP) mode. To maintain a high level of service capability in community comprehensive elderly care service facilities under PPP mode, scientific evaluation of the effectiveness of these facilities is equally crucial. This article first constructs a post-occupancy evaluation index system of community comprehensive elderly care service facilities under PPP mode that includes three evaluation attributes and fifteen evaluation criteria based on the Chinese culture and lifestyle habits. Regarding the issue of direct users being unable to directly participate in evaluations, the uncertainty in evaluation information, and the volatility of evaluation results, a multi-stage post-occupancy evaluation model is constructed based on probabilistic linguistic term set, TOPSIS model and multi-stage decision theory. The above post-occupancy evaluation index system and evaluation model together constitute a multi-stage post-occupancy evaluation framework for community comprehensive elderly care service facilities under PPP mode. The outcomes of the case study indicate that the post-occupancy evaluation index system can offer a scientifically guided approach for evaluating the service level of community comprehensive elderly care service facilities under the PPP mode; meanwhile, the multi-stage evaluation model can enable direct user participation in the post-evaluation of facility usage and improve the robustness and reduce the fluctuation of the evaluation results, so as to improve the scientificity of the evaluation results.

In recent years, the number of Chinese Christian organizations in Europe has grown considerably compared to other overseas Chinese community organizations. They can mobilize transnational networks and resources to expand religious space in host societies and form a highly visible social force. Although the rise of early Christianity in the Western world has been considered an outcome of inherent religious strength, especially in terms of its central doctrines and religious ethics, this article suggests that in the diasporic Chinese world where Christianity constitutes a non-indigenous religious tradition, social relatedness based on native place, family, and kinship ties provides a more useful context for understanding its dynamic expansion and cross-regional transmission. Drawing on anthropological fieldwork conducted in Europe among overseas Chinese Christian traders and entrepreneurs, this research seeks an alternative framework for understanding the religious-cultural dynamics of Chinese Christianity in the context of transnational migration.

Low carbonization of the traction system is the key to low-carbon rail transit operation, and its preliminary plan decision plays a decisive role in whether low carbon can be achieved in later stages. Therefore, how to achieve scientific decisions of energy storage traction systems in a low-carbon background is a problem that needs to be solved. The innovation of this paper is as follows: first, aiming at the reality of the rail transit energy storage traction system, a decision index system of the energy storage traction system which contains seven attributes and 18 criteria is constructed; second, aiming at the uncertainty of decision information and the decision makers’ aversion to risk, the decision model adapted to the energy storage traction system decision is constructed based on the interval Pythagorean intuitionistic fuzzy number and VIKOR model principle. The decision index system and decision model together constitute the decision framework. The case study results show that the decision index system can provide scientific guidance for the decision of the energy storage traction system, and the decision model can provide risk aversion type decision results with good robustness.

ObjectiveTo investigate the adult iodine nutrition and the prevalence of thyroid diseases in Qinghai Province, and analyze the correlation between iodine and thyroid diseases, so as to provide a basis for adjusting the salt iodization plan in Qinghai Province.MethodsUsing cluster and stratified sampling method to select 2628 permanent residents over 18 years old in Qinghai Province for questionnaire survey, physical examination, thyroid color ultrasound, and laboratory index detection.Results1. The coverage of iodized salt in adults is 99.71%. 2. The detection rates of thyroid disorders in adults were as follows: Clinical hyperthyroidism was 1.20%, subclinical hyperthyroidism was 0.20%, clinical hypothyroidism was 1.00%, subclinical hypothyroidism was 29.20%, and the goiter was 2.10%. The percentages positivity of TPO Ab, TG Ab, goiter was 9.80%, 9.20%, 2.10%, respectively. Among them single thyroid nodule was 6.40%, multi-nodule thyroid gland was 1.80%. 3. The percentages of mild iodine deficiency, moderate iodine deficiency, Severe iodine deficiency, adequate iodine intake (AI), more than adequate iodine intake (MAI)and excessive iodine intake (EI)were 8.41%, 2.17%, 0.26%, 33.22%, 28.35%, and 27.59%, respectively. The percentages of mild, moderate and severe iodine deficiency in urban populations (7.13%, 0.87%, 0.0%) were significantly lower than those in rural populations (9.81%, 3.59%, 0.56%) (P < 0.05), and the rates of adequate, more than adequate iodine intake in urban populations (36.03%, 30.93%) were significantly higher than that in rural populations (30.14%, 25.52%). The rate of excess iodine intake was higher in rural areas (30.38%) than in urban areas (25.04%). 4. The positive rates of subclinical hypothyroidism, goiter, TPO Ab and TG Ab in female adults (35.28%, 3.39%, 13.54%, 13.94%) were higher than those in male adults (23.58%, 0.96%, 6.266%, 4.79%). The detection rate of single thyroid nodules was higher in urban (8.01%) than rural populations (4.70%), while the detection rate of hypothyroidism, subclinical hypothyroidism, and goiter (0.58%, 25.84%, 1.38%) was lower than that in rural populations (1.52%, 32.96%, 2.96%) (P0.05). The positive rate of hypothyroidism in the iodine deficiency group is higher than in other iodine nutrition groups.ConclusionThe nutritional status of iodine in Qinghai Province is iodine excess. Subclinical hypothyroidism was detected at a high rate. Subclinical hypothyroidism, goiter, TPO Ab, and TG Ab were more common in female than in male. The proportion of mild, moderate, and severe iodine deficiency was higher in urban areas than in rural areas. The detection rate of thyroid nodules was higher in urban than in rural areas, and that of hypothyroidism, subclinical hypothyroidism, and goiter was lower than that in rural populations. The detection rate of clinical hypothyroidism was statistically significant in different iodine nutritional states (P< 0.05).

Abstract Background Osteosarcoma (OSA) is the most prevalent type of bone cancer with a high rate of metastasis. Circular RNAs (CircRNAs) play an essential role in multiple aspects of tumour biology. This study aimed to elucidate the role of circEMB in OSA. Methods circRNAs related to OSA invasion were identified via RNA sequencing and qRT-PCR. The relationship between circEMB levels and clinicopathological features of OSA was examined using the clinical specimens and data of 53 patients with OSA. Several in vivo and in vitro experiments, including intravital imaging, whole-transcriptome sequencing, transwell assay, flow cytometry, dual-luciferase reporter assay, RIP assay, RNA pull-down assay and RNA-FISH, were performed to examine the effects of circEMB on the malignant behaviour of OSA. Results A novel circRNA, named circEMB (hsa_circ_001310), was identified in this study. circEMB can promote the malignant behaviour of OSA. In vitro experiments revealed that circEMB knockdown decreased cell proliferation, inhibited tumour invasion and metastasis; increased apoptosis and resulted in G1/S phase arrest. In vivo experiments revealed that circEMB knockdown inhibited tumour growth and metastasis in xenograft-bearing mice. Mechanistically, circEMB affects the malignant behaviour of OSA by mediating EGFR as an miR-3184-5p sponge. In addition, the circEMB/miR-3184-5p/EGFR axis modulates methotrexate (MTX) resistance in OSA. Conclusions CircEMB plays a critical role in promoting cancer via the miR-3184-5p/EGFR pathway, indicating that circEMB may serve as a therapeutic target for OSA.

Objectives Ensuring the accuracy of transclavicular‐transcoracoid drilling in the anatomical reconstruction of the coracoclavicular ligament complex with minimally invasive incisions remains a major problem for inexperienced surgeons. The purpose of this study was to design an assembly guide device for transclavicular‐transcoracoid drilling with minimally invasive incisions, to manufacture the finished product, and to compare its feasibility and accuracy with the existing C‐shape guide devices and free‐hand techniques. Methods An assembly‐type guide device was designed and produced using computer‐aided design and three‐dimensional printing. The specimen data of 54 human shoulders from 27 gross specimen (14 males and 13 females) treated by free‐hand drilling, C‐shape device drilling, and assembly‐type guide device drilling from October 2018 to January 2021 were analyzed in a controlled laboratory study. Fifty‐four human shoulder specimens were randomly assigned into free‐hand (n = 18), C‐shape (n = 18), and assembly (n = 18) groups by drawing lots for transclavicular‐transcoracoid drilling by three inexperienced surgeons. After the drilling procedure was completed and the devices were removed, the operation outcomes were assessed and evaluated. Distances from the tunnel edge to the coracoid's medial (dm) and lateral (dl) edges, operation time, and tunnel location zones on the coracoid's inferior surface of all specimens in the three groups were measured to evaluate the surgical accuracy and efficiency. Results All specimens in the three groups completed the drilling operation successfully and were correctly measured. The distance differences (dd) between dm and dl in the free‐hand, C‐shape, and assembly groups were 3.2 ± 1.8 mm, 1.8 ± 1.0 mm, 1.0 ± 0.8 mm, respectively. The dd of the free‐hand group was higher than that of the other two groups (p

The mitochondrial genome (mitogenome or mtDNA), the extrachromosomal genome, is a multicopy circular DNA with high mutation rates due to replication and repair errors. A mitochondrion, cell, tissue, organ, or an individual body may hold multiple variants, both inherited and developed over a lifetime, which make up individual mitogene pools. This phenomenon is also called mtDNA heteroplasmy. MtDNA variants influence cellular and tissular functions and are consequently subjected to selection. Although it has long been recognized that only inheritable germline heteroplasmies have evolutionary significance, non-inheritable somatic heteroplasmies have been overlooked since they directly affect individual fitness and thus indirectly affect the fate of heritable germline variants. This review focuses on the characteristics, dynamics, and functions of mtDNA heteroplasmy and proposes the concept of individual mitogene pools to discuss individual genetic diversity from multiple angles. We provide a unique perspective on the relationship between individual genetic diversity and heritable genetic diversity and guide how the individual mitogene pool with novel genetic markers can be applied to ecological research.

Background: Osteosarcoma is the most common primary pediatric and adolescent bone malignancy. An imbalance in copper homeostasis caused by copper ion accumulation could increase intracellular toxicity and regulate cancer cell growth. This study aimed to identify long non-coding RNAs (lncRNAs) associated with cuproptosis to predict prognosis and target drug use to improve patient survival. Methods: RNA sequencing and relevant clinical information of ninety-three osteosarcoma patients were obtained from the TARGET database. We then identified thirteen prognostic cuproptosis-related lncRNAs(CRLncs) using coexpression and univariate Cox analyses. The prognostic risk model with three CRLncs was constructed using the least absolute shrinkage and selection operator (LASSO) and multivariate Cox regression analysis. Patients were divided into low-risk and high-risk subgroups using the median risk score. The tumor microenvironment (TME) and immune status of identified subgroups were analyzed using ESTIMATE, CIBERSORT, MCP-counter, xCELL, EPIC, and ssGSEA analyses. Functional analyses were conducted to elucidate the underlying mechanisms, including GO, KEGG, GSVA, and GSEA analyses. Also, the relationships between the model, tumor immunity, and drug sensitivity were explored. Lastly, the expression level of ZNF37BP, AL353759.1, and AC005034.5 was validated in vitro. Results: We constructed a model containing three CRLncs (ZNF37BP, AL353759.1, and AC005034.5) and validated its excellent prognostic and predictive power. The AUC curves for 1-year, 3-year, and 5-year survival probabilities were 0.76, 0.84, and 0.89, respectively. Patients in the high-risk group had a shorter overall survival (OS) time than those in the low-risk. The stroma score and cancer-associated fibroblasts (CAFs) were significantly higher in the low-risk group. Immune cells such as T cells CD4 naive, T cells gamma delta, NK cells resting, dendritic cells resting, and mast cells activated were significantly upregulated in the high-risk group. Based on functional analyses, the PI3K-Akt pathway was identified as a critical metabolic pathway in osteosarcoma. Additionally, we obtained three potentially effective drugs for OS: erlotinib, MP470, and WH-4-023 targeting the PI3K-Akt pathway. The expression level of ZNF37BP was significantly elevated in OS cell lines than in normal osteoblast hFOB1.19 cells, and that of ATP7A, LIPT1, AL353759.1, and AC005034.5 were decreased considerably in OS cell lines. Conclusion: Cuproptosis-related lncRNAs are correlated with the CAFs of osteosarcoma, and this could serve as a foundation for OS survival prediction and treatment.

Pinch1 and Pinch2 are LIM domain-containing proteins with crucial functions in mediating focal adhesion formation. Our previous studies have demonstrated that Pinch1/2 expression is essential for cartilage and bone formation during skeletal development in mice. Loss of Pinch expression (Prx1Cre; Pinch1flox/flox; Pinch2−/−) inhibits chondrocyte proliferation and promotes chondrocyte apoptosis, resulting in severe chondrodysplasia and limb shortening. Based on these observations, we wonder if Pinch proteins have a role in adult cartilage and whether Pinch deficiency will compromise cartilage homeostasis and promote osteoarthritis (OA)-related defects in adult mice. To this end, we generated the AggrecanCreERT2; Pinch1flox/flox; Pinch2−/− mice, in which the Pinch1 gene can be inducibly deleted in aggrecan-expressing chondrocytes by tamoxifen and the Pinch2 gene is globally inactivated. Immunofluorescent staining confirmed that the expression of Pinch proteins was significantly decreased in articular cartilage in tamoxifen-treated adult AggrecanCreERT2; Pinch1flox/flox; Pinch2−/− mice. Unexpectedly, our results showed that Pinch loss did not induce marked abnormalities in articular cartilage and other joint tissues in the knee joints of either adult (10-month-old) mice or aged (17-month-old) mice. In a destabilization of the medial meniscus (DMM)-induced OA model, the surgically-induced OA lesions were comparable between Pinch-deficient mice and control mice. Given the fact that Pinch proteins are essential for chondrogenesis and cartilage formation during skeletal development, these findings suggest that Pinch expression is seemingly not indispensable for adult cartilage homeostasis in mice.

Abstract Background Circular RNAs (circRNAs) are involved in diverse processes that drive cancer development. However, the expression landscape and mechanistic function of circRNAs in osteosarcoma (OS) remain to be studied. Methods Bioinformatic analysis and high-throughput RNA sequencing tools were employed to identify differentially expressed circRNAs between OS and adjacent noncancerous tissues. The expression level of circ_001422 in clinical specimens and cell lines was measured using qRT-PCR. The association of circ_001422 expression with the clinicopathologic features of 55 recruited patients with OS was analyzed. Loss- and gain-of-function experiments were conducted to explore the role of circ_001422 in OS cells. RNA immunoprecipitation, fluorescence in situ hybridization, bioinformatics database analysis, RNA pulldown assays, dual-luciferase reporter assays, mRNA sequencing, and rescue experiments were conducted to decipher the competitive endogenous RNA regulatory network controlled by circ_001422. Results We characterized a novel and abundant circRNA, circ_001422, that promoted OS progression. Circ_001422 expression was dramatically increased in OS cell lines and tissues compared with noncancerous samples. Higher circ_001422 expression correlated with more advanced clinical stage, larger tumor size, higher incidence of distant metastases and poorer overall survival in OS patients. Circ_001422 knockdown markedly repressed the proliferation and metastasis and promoted the apoptosis of OS cells in vivo and in vitro, whereas circ_001422 overexpression exerted the opposite effects. Mechanistically, competitive interactions between circ_001422 and miR-195-5p elevated FGF2 expression while also initiating PI3K/Akt signaling. These events enhanced the malignant characteristics of OS cells. Conclusions Circ_001422 accelerates OS tumorigenesis and metastasis by modulating the miR-195-5p/FGF2/PI3K/Akt axis, implying that circ_001422 can be therapeutically targeted to treat OS.

The osteosarcoma (OS) microenvironment is composed of tumor cells, immune cells, and stromal tissue and is emerging as a pivotal player in OS development and progression. Thus, microenvironment-targeted strategies are urgently needed to improve OS treatment outcomes. Using principal component analysis (PCA), we systematically examined the tumor microenvironment (TME) and immune cell infiltration of 88 OS cases and constructed a TME scoring system based on the TMEscore high and TMEscore low phenotypes. Our analysis revealed that TMEscore high correlates with longer survival in OS patients, elevated immune cell infiltration, increased immune checkpoints, and increased sensitivity to chemotherapy. TMEscore low strongly correlated with immune exclusion. These observations were externally validated using a GEO dataset (GSE21257) from 53 OS patients. Our laboratory data also proved our findings. This finding enhances our understanding of the immunological landscape in OS and may uncover novel targeted therapeutic strategies.

Background: To explore possible predictors of severe late ovarian hyperstimulation syndrome (SL-OHSS) in fresh embryo transfer cycles. Methods: We conducted a historical cohort study in a Chinese tertiary hospital from January 2017 to December 2019, with a total of 6931 women who had the first fresh embryo transfer included. SL-OHSS was defined as severe symptoms of OHSS occurring 12–17 days after ovulation triggering. Possible determinants of the occurrence of SL-OHSS were identified by a detection decision tree, effects of which were estimated by conditional logistic regression and restricted cubic spline. Results: Elevated estradiol (E2) on the day of ovulation triggering and elevated Anti-Mullerian hormone (AMH) were associated with an increased risk of SL-OHSS (p < 0.001). Women with an E2 on trigger day of ≥3320.2 pg/mL (odds ratio (OR): 2.20; 95% confidence interval (CI): 1.03–4.68), or with an E2 on trigger day of 3320.2 pg/mL and AMH of >4.62 ng/mL had the highest risk of SL-OHSS (OR: 13.20; 95% CI: 3.87–45.02) when compared with E2 on trigger day of ≤3320.2 pg/mL and AMH of ≤4.62 ng/mL. This association was not linear. Conclusions: Serum E2 concentration on trigger day and AMH levels at baseline may predict SL-OHSS occurrence in fresh embryo transfer cycles. These biomarkers may be valuable in determining the optimum transfer strategy to limit the occurrence of SL-OHSS.

Abstract Background The transoral atlantoaxial reduction plate (TARP) is an effective advance in the treatment of atlantoaxial dislocation (AAD) and can enable the performance of anterior atlantoaxial release, reduction, decompression, and internal fixation in a one-stage operation. However, accurate transoral C2 pedicle insertion (C2TOPI) remains a challenge. The aim of this study is to develop a grouped patient-specific drill template (PDT) specifically for AAD with complete reduction and, furthermore, to compare its efficacy and accuracy in facilitating C2TOPI. Methods After CT scanning, ten cadaveric C2 specimens were randomly assigned to two groups (the PDT and freehand group). A grouped PDT specifically for AAD with complete reduction was designed and manufactured. C2TOPI was performed using the PDT or the fluoroscopy-guided freehand technique. Postoperative CT scans were subsequently performed to analyze the deviations at the centroid of the cross section at the midpoint of the pedicle. Screw position grades were also assessed in both groups. Results Compared to the freehand group, the PDT group had a significantly shorter surgery time (p 0.05); however, two unacceptable breaches (20%) occurred in the freehand group. Conclusion A specifically designed PDT could provide an accurate and easy-to-apply method for C2TOPI in AAD with complete reduction.

The traditional dynamic characteristic analysis of the multi-stage centrifugal pump rotor system is developed assuming the bearing structural parameters with constant values. However, the manufacturing errors will cause the structural parameters to vary around their nominal values and then affect the dynamic characteristics of the bearing-rotor system. Thus, this paper proposes a method for analyzing the dynamic characteristics of the bearing-rotor system with uncertain bearing structural parameters. First, dynamic characteristic coefficients of the sliding bearing are identified to establish the dynamic model of the rotor system, and its dynamic characteristics are analyzed through finite element simulations. Next, the sliding bearing structural parameters are taken as the variables to establish an optimization model, which is solved by the improved particle swarming optimization algorithm to obtain the extreme critical speed of the rotor system. A case study was carried out on a multi-stage centrifugal pump. The obtained extreme values of the critical speeds were close to those calculated using the multiple samples generated by the Monte Carlo method, indicating that the proposed method can provide accurate variation ranges of critical speeds efficiently and lay a theoretical basis for selecting robust operational speeds and designing the rotor system of the multi-stage centrifugal pump.

Staged fracturing horizontal well technology is an important means of improving tight reservoir development efficiency. Taking a typical tight oil block in the Oilfield A as the studied area, the vertical well–horizontal well joint arrangement pattern is adopted in this study. The energy supplementary development effects of multiple permeability scales, different arrangement spacing, and different media (H 2 O, CO 2 ) are discussed through the numerical simulation method. Combined with the principles of petroleum technology economics, the economic evaluation model for staged fracturing horizontal wells in tight oil reservoir development is proposed, thereby determining the technical boundary and economic boundary of supplementary energy development with different media. Studies indicate that the technical boundary and economic boundary of water-flooding development in the Oilfield A are 0.4 and 0.8 mD, respectively, and the technical boundary and economic boundary of CO 2 -flooding development are 0.1 and 0.4 mD, respectively. This study provides theoretical support for field operation of Oilfield A and guidance for selection of development mode for tight oil reservoirs.

Background: Wound closure is highly associated with wound complications and the best wound closure method was controversial in total hip arthroplasty. Methods: We performed a retrospective study of primary hip arthroplasty and compared three types of closure method. Results: 155 cases were closed using continuous subcuticular sutures then with staples, 111 using staples, 141 using interrupted sutures. 28 cases of wound complications occurred. Wound complication rates in subcuticular suture group, staple group and interrupted suture group were 1.9%, 11.7% and 8.5%, respectively (p

Stability is the prerequisite of a milling operation, and it seriously depends on machining parameters and machine tool dynamics. Considering that the tool information, including the tool clamping length, feeding direction, and spatial position, has significant effects on machine tool dynamics, this paper presents an efficient method to predict the tool information dependent-milling stability. A generalized regression neural network (GRNN) is established to predict the limiting axial cutting depth, where the machining parameters and tool information are taken as input variables. Moreover, an optimization model is proposed based on the machining parameters and tool information to maximize the material removal rate (MRR), where the GRNN model is taken as the stability constraint. A particle swarm optimization (PSO) algorithm is introduced to solve the optimization model and provide an optimal configuration of the machining parameters and tool information. A case study has been developed to train a GRNN model and establish an optimization model of a real machine tool. Then, effects of the tool information on milling stability were discussed, and an origin-symmetric phenomenon was observed as the feeding direction varied. The accuracy of the solved optimal process parameters corresponding to the maximum MRR was validated through a milling test.

To investigate the association of combined microRNA-340 (miR-340) and ROCK1 mRNA profiling with clinicopathologic features and prognosis in pediatric patients with osteosarcoma. Quantitative real-time reverse transcriptase-polymerase chain reaction analysis was performed to detect expression levels of miR-340 and ROCK1 mRNA in cancerous and noncancerous bone tissues from 92 children treated for primary osteosarcomas. Compared with noncancerous bone tissues, the expression levels of miR-340 and ROCK1 mRNA were, respectively, downregulated and upregulated in osteosarcoma tissues (both p < 0.001), which was consistent with the results of in situ hybridization and immunohistochemistry analysis. The downregulation of miR-340 was negatively correlated with the upregulation of ROCK1 mRNA in osteosarcoma tissues (r = −0.78, p = 0.001). In addition, the combined miR-340 downregulation and ROCK1 upregulation (miR-340-low/ROCK1-high) occurred more frequently in osteosarcoma tissues with positive metastasis (p < 0.001) and poor response to pre-operative chemotherapy (p = 0.002). Moreover, miR-340-low/ROCK1-high expression was significantly associated with both shortest overall survival (p < 0.001) and progression-free survival (p < 0.001). Multivariate analysis further confirmed that miR-340-low/ROCK1-high expression was an independent prognostic factor of unfavorable survival in pediatric osteosarcoma (for overall survival: p = 0.006, for progression-free survival: p = 0.008). Our data offer convincing evidence, for the first time, that the combined miR-340 downregulation and ROCK1 upregulation may be linked to tumor progression and adverse prognosis in pediatric osteosarcoma.

BACKGROUND: With the properties of three-column fixation and anterior-approach-only procedure, anterior transpedicular screw (ATPS) is ideal for severe multilevel traumatic cervical instabilities. However, the accurate insertion of ATPS remains challenging. Here we constructed a patient-specific biocompatible drill template and evaluated its accuracy in assisting ATPS insertion. METHODS: After ethical approval, 24 formalin-preserved cervical vertebrae (C2-C7) were CT scanned. 3D reconstruction models of cervical vertebra were obtained with 2-mm-diameter virtual pin tracts at the central pedicles. The 3D models were used for rapid prototyping (RP) printing. A 2-mm-diameter Kirschner wire was then inserted into the pin tract of the RP model before polymethylmethacrylate was used to construct the patient-specific biocompatible drill template. After removal of the anterior soft tissue, a 2-mm-diameter Kirschner wire was inserted into the cervical pedicle with the assistance of drill template. Cadaveric cervical spines with pin tracts were subsequently scanned using the same CT scanner. A 3D reconstruction was performed of the scanned spines to get 3D models of the vertebrae containing the actual pin tracts. The deviations were calculated between 3D models with virtual and actual pin tracts at the middle point of the cervical pedicle. 3D models of 3.5 mm-diameter screws were used in simulated insertion to grade the screw positions. FINDINGS: The patient-specific biocompatible drill template was constructed to assist ATPS insertion successfully. There were no significant differences between medial/lateral deviations (P = 0.797) or between superior/inferior deviations (P = 0.741). The absolute deviation values were 0.82±0.75 mm and 1.10±0.96 mm in axial and sagittal planes, respectively. In the simulated insertion, the screws in non-critical position were 44/48 (91.7%). CONCLUSIONS: The patient-specific drill template is biocompatible, easy-to-apply and accurate in assisting ATPS insertion. Its clinical applications should be further researched.

The potential of grazing lands to sequester carbon must be understood to develop effective soil conservation measures and sustain livestock production. Our objective was to evaluate the effects of grazing on soil organic carbon (SOC), total nitrogen (TN), microbial biomass carbon (MBC) in Typical steppe and Desert steppe ecosystems, which are both important grassland resources for animal grazing and ecological conservation in China, and to derive region-specific soil C changes associated with different stocking rates (ungrazed, UG; lightly grazed, LG; moderately grazed, MG; heavily grazed, HG). This study substantiated that significant higher SOC, TN and MBC appeared with the treatment of LG in typical steppe. From 2004 to 2010, grazing treatments increased soil carbon storage in desert steppe, which was partly due to the grazing history. The higher MBC concentration and MBC/SOC suggest a great potential for carbon sequestration in the desert steppe ecosystem. The greater MBC in desert steppe than typical steppe was mainly the result of higher precipitation and temperature, instead of soil substrate. The change of MBC and the strong positive relationships between MBC and SOC indicated that MBC in the soil was a sensitive index to indicate the dynamics of soil organic carbon in both steppes in Inner Mongolia of China.

Objective: While platelet rich plasma (PRP) has been extensively studied in treating osteoarthritis (OA), there has been an ongoing debate regarding the efficacy of PRP and the optimal subpopulation for PRP treatment remains unknown. The authors hereby aim to establish a pharmacodynamic model-based meta-analysis to quantitatively evaluate PRP efficacy, comparing with hyaluronic acid (HA) and identify relevant factors that significantly affect the efficacy of PRP treatment for OA. Methods: The authors searched for PubMed and the Cochrane Library Central Register of Controlled Trials of PRP randomized controlled trials (RCTs) for the treatment of symptomatic or radiographic OA from the inception dates to 15 July 2022. Participants' clinical and demographic characteristics and efficacy data, defined as Western Ontario and McMaster Universities Osteoarthritis Index and visual analog scale pain scores at each time point were extracted. Results: A total of 45 RCTs (3829 participants) involving 1805 participants injected with PRP were included in the analysis. PRP reached a peak efficacy at ~ 2-3 months after injection in patients with OA. Both conventional meta-analysis and pharmacodynamic maximal effect models showed that PRP was significantly more effective than HA for joint pain and function impairment (additional decrease of 1.1, 0.5, 4.3, and 1.1 scores compared to HA treatment at 12 months for Western Ontario and McMaster Universities Osteoarthritis Index pain, stiffness, function, and visual analog scale pain scores, respectively). Higher baseline symptom scores, older age (=60 years), higher BMI (=30), lower Kellgren-Lawrence grade (=2) and shorter OA duration (< 6 months) were significantly associated with greater efficacy of PRP treatment. Conclusion: These findings suggest that PRP is a more effective treatment for OA than the more well-known HA treatment. The authors also determined the time when the PRP injection reaches peak efficacy and optimized the targeting subpopulation of OA. Further high-quality RCTs are required to confirm the optimal population of PRP in the treatment of OA. [ABSTRACT FROM AUTHOR]

Abstract Background Preeclampsia, especially early-onset preeclampsia (EO-PE), is a pregnancy complication that has serious consequences for the health of both the mother and the fetus. Although abnormal placentation due to mitochondrial dysfunction is speculated to contribute to the development of EO-PE, the underlying mechanisms have yet to be fully elucidated. Methods The expression and localization of Siglec-6 in the placenta from normal pregnancies, preterm birth and EO-PE patients were examined by RT-qPCR, Western blot and IHC. Transwell assays were performed to evaluate the effect of Siglec-6 on trophoblast cell migration and invasion. Seahorse experiments were conducted to assess the impact of disrupting Siglec-6 expression on mitochondrial function. Co-IP assay was used to examine the interaction of Siglec-6 with SHP1/SHP2. RNA-seq was employed to investigate the mechanism by which Siglec-6 inhibits mitochondrial function in trophoblast cells. Results The expression of Siglec-6 in extravillous trophoblasts is increased in placental tissues from EO-PE patients. Siglec-6 inhibits trophoblast cell migration and invasion and impairs mitochondrial function. Mechanismly, Siglec-6 inhibits the activation of NF-κB by recruiting SHP1/SHP2, leading to increased expression of GPR20. Notably, the importance of GPR20 function downstream of Siglec-6 in trophoblasts is supported by the observation that GPR20 downregulation rescues defects caused by Siglec-6 overexpression. Finally, overexpression of Siglec-6 in the placenta induces a preeclampsia-like phenotype in a pregnant mouse model. Conclusions This study indicates that the regulatory pathway Siglec-6/GPR20 has a crucial role in regulating trophoblast mitochondrial function, and we suggest that Siglec-6 and GPR20 could serve as potential markers and targets for the clinical diagnosis and therapy of EO-PE.

Abstract Selective inhibition of the transcription elongation factor (P‐TEFb) complex represents a promising approach in cancer therapy, yet CDK9 inhibitors (CDK9i) are currently limited primarily to certain hematological malignancies. Herein, while initial responses to CDK9‐targeted therapies are observed in vitro across various KRAS‐mutant cancer types, their efficacy is far from satisfactory in nude mouse xenograft models. Mechanistically, CDK9 inhibition leads to compensatory activation of ERK‐MYC signaling, accompanied by the recovery of proto‐oncogenes, upregulation of immediate early genes (IEGs), stimulation of the complement C1r‐C3‐C3a cascade, and induction of tumor immunosuppression. The “paradoxical” regulation of PP2Ac activity involving the CDK9/Src interplay contributes to ERK phosphorylation and pause‐release of RNA polymerase II (Pol II). Co‐targeting of CDK9 and KRAS/MAPK signaling pathways eliminates ERK‐MYC activation and prevents feedback activation mediated by receptor tyrosine kinases, leading to more effective control of KRAS‐mutant cancers and overcoming KRASi resistance. Moreover, modulating the tumor microenvironment (TME) by complement system intervention enhances the response to CDK9i and potently suppresses tumor growth. Overall, the preclinical investigations establish a robust framework for conducting clinical trials employing KRASi/SOS1i/MEKi or immunomodifiers in combination with CDK9i to simultaneously target cancer cells and their crosstalk with the TME, thereby yielding improved responses in KRAS‐mutant patients.

ABSTRACT The HIV reservoir is more dynamic than previously thought with around 70% of the latent reservoir originating from viruses circulating within 1 year of the initiation of antiretroviral therapy (ART). In an ex vivo model system of HIV latency, it was reported that early exposure to class I histone deacetylase (HDAC) inhibitors might prevent these more recently infected cells from entering a state of stable viral latency. This finding raises the possibility that co-administration of HDAC inhibitors at the time of ART initiation may prevent the establishment of much of the HIV reservoir. Here, we tested the effects of the HDAC inhibitors suberoylanilide hydroxamic acid (SAHA) and panobinostat co-administered at the time of ART initiation on the formation of the viral reservoir in HIV-infected humanized mice. As previously shown, SAHA and panobinostat were well tolerated in humanized mice. Unexpectedly, co-administration of SAHA resulted in an increase in the frequency of CD4+ cells carrying HIV DNA but did not alter the frequency of cell-associated HIV RNA in HIV-infected, ART-treated humanized mice. Co-administration of panobinostat did not alter levels of cell-associated HIV DNA or RNA. Our in vivo findings indicate that co-administration of HDAC inhibitors initiated at the same time of ART treatment does not prevent recently infected cells from entering latency.IMPORTANCECurrent antiretroviral therapy (ART) does not eradicate cells harboring replication-competent HIV reservoir. Withdrawal of ART inevitably results in a rapid viremia rebound. The HIV reservoir is more dynamic than previously thought. Early exposure to class I histone deacetylase (HDAC) inhibitors inhibit these more recently infected cells from entering a state of stable viral latency in an ex vivo model of latency, raising the possibility that co-administration of HDAC inhibitors at the time of ART initiation may reduce much of the HIV reservoir. Here, we tested the effects of the HDAC inhibitors suberoylanilide hydroxamic acid or panobinostat during ART initiation on the formation of the viral reservoir in HIV-infected humanized mice. Our in vivo study indicates that in contrast to in vitro observations, the co-administration of HDAC inhibitors at the same time of ART initiation does not prevent recently infected cells from entering latency.