Interrelationships among abnormal P-wave axis, metabolic syndrome and its components, and mortality in US adults.

BACKGROUND: Metabolic syndrome (MetS) is associated with increased rates of cardiovascular disease and mortality and is linked to abnormal electrocardiogram (ECG) parameters. We aimed to explore the relationships and interactions among MetS and its components, abnormal P-wave axis (aPWA), and mortality rates. METHODS: We analyzed data from 7526 adult participants with sinus rhythm recruited from the National Health and Nutrition Examination Survey III. MetS was classified based on the NCEP ATP III-2005 definition. aPWA included all P-wave axis outside 0-75°. The National Death Index was utilized to identify survival status. Hazard ratios (HRs) and 95% confidence intervals (CIs) categorized by aPWA, MetS, and their components were analyzed using Cox proportional hazards models to investigate all-cause and cardiovascular mortalities. RESULTS: Within a median follow-up period of 20.76 years, 4686 deaths were recorded, of which 1414 were attributable to cardiovascular disease. Participants with both MetS and aPWA had higher all-cause (HR: 1.45, 95% CI: 1.29-1.64, interaction P = 0.043) and cardiovascular (HR: 1.36, 95% CI: 1.02-1.79, interaction P-value = 0.058) mortality rates than participants without MetS and with a normal P-wave axis. Participants with the greatest number of MetS components and aPWA had a higher risk of all-cause mortality (HR: 1.70, 95% CI: 1.13-2.55, P = 0.011). CONCLUSIONS: Individuals with both aPWA and MetS have a higher risk of mortality, and those with a greater number of MetS components and aPWA have a higher risk of all-cause mortality. These findings highlight the significance of integrating ECG characteristics with metabolic health status in clinical assessment.

Cu-Tremella fuciformis polysaccharide-based tumor microenvironment-responsive injectable gels for cuproptosis-based synergistic osteosarcoma therapy.

Cuproptosis affects osteosarcoma locally, and the exploitation of cuproptosis-related biomaterials for osteosarcoma treatment is still in its infancy. We designed and synthesized a novel injectable gel of Cu ion-coordinated Tremella fuciformis polysaccharide (TFP-Cu) for antiosteosarcoma therapy. This material has antitumor effects, the ability to stimulate immunity and promote bone formation, and a controlled Cu2+ release profile in smart response to tumor microenvironment stimulation. TFP-Cu can selectively inhibit the proliferation of K7M2 tumor cells by arresting the cell cycle and promoting cell apoptosis and cuproptosis. TFP-Cu also promoted the M1 polarization of RAW264.7 cells and regulated the immune microenvironment. These effects increased osteogenic gene and protein expression in MC3T3-E1 cells. TFP-Cu could significantly limit tumor growth in tumor-bearing mice by inducing tumor cell apoptosis and improving the activation of anti-CD8 T cell-mediated immune responses. Therefore, TFP-Cu could be a potential candidate for treating osteosarcoma and bioactive drug carrier for further cancer-related applications.

Noncoding RNAs in skeletal development and disorders.

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.

Community integration and its predictors in people with stroke: a multicenter longitudinal study.

OBJECTIVE: To investigate the community integration of patients following stroke and determine the predictors of their level of community integration at 1-year follow-up. DESIGN: A multicenter, longitudinal, and observational study. SUBJECTS: Sixty-five inpatients (41 men) with a mean age of 56.9 (standard deviation = 17.0) years, who had their first stroke at least 1 month prior to this study were recruited from 4 rehabilitation inpatient wards in China. METHODS: In the initial assessment, the participants were evaluated using the Community Integration Questionnaire, the Fugl-Meyer Assessment, the Berg Balance Scale, the Modified Barthel Index, the Mini Mental State Examination, and the Modified Ashworth Scale. In the follow-up assessments, which were conducted via telephone no less than 1 year after discharge, the participants were evaluated using the Community Integration Questionnaire and also assessed for other disease-related conditions. RESULTS: The participants' scores on the Community Integration Questionnaire in the follow-up assessment were significantly greater than those at the initial assessment (p < 0.05). In addition, the participants' Community Integration Questionnaire scores in the follow-up assessment were significantly correlated with their ages, numbers of years of education, and Modified Barthel Index, Berg Balance Scale, Mini Mental State Examination scores in the initial assessment (p < 0.05), and marginally significantly correlated with their scores on Fugl-Meyer Assessment in the initial assessment (p = 0.058). The participants' ages, numbers of years of education, and Modified Barthel Index, Berg Balance Scale, Mini Mental State Examination, Fugl-Meyer Assessment of the lower extremity, and Fugl-Meyer Assessment scores in the initial assessment were predictive of their Community Integration Questionnaire scores at follow-up, with coefficients of determination ranging from 0.254 to 0.056 (p < 0.05). CONCLUSIONS: The level of community integration of the participants was generally low, but it was greater at 1-year follow-up than it was initially. Balance function and daily living ability may be key predictors of community integration of patients following stroke.

Clinical utility of office hysteroscopy following failed in vitro fertilization-embryo transfer: A retrospective cohort study.

OBJECTIVE: Despite its widespread use, in vitro fertilization (IVF) outcomes are challenged by implantation failure, largely due to factors such as embryo quality and endometrial receptivity. In this study, we investigated the clinical effect of office hysteroscopy (OH) on the subsequent frozen-thawed embryo transfer (FET) in infertile women who experienced a failed IVF-embryo transfer (IVF-ET) cycle. METHODS: We included 577 infertile women who underwent OH because of a history of failed ET between October 2019 and September 2021. During OH, visible endometrial polyps (EPs) were diagnosed and removed by curette or biopsy forceps; chronic endometritis (CE) was diagnosed by histopathology and immunohistochemistry and treated with oral doxycycline (0.2 g/d) for 14 days. According to the hysteroscopic findings and endometrial pathology with immunohistochemistry, patients were divided into three groups: group A (n = 161) had CE with or without EPs, group B (n = 156) had EPs only, and group C (n = 260) had no CE or EPs. RESULTS: In the following FET cycle, the implantation rates were 47%, 51%, and 45% (P = 0.411); the clinical pregnancy rates were 56%, 62%, and 55% (P = 0.436); the live birth rates were 45%, 51%, and 42% (P = 0.205); and the miscarriage rates were 18%, 16%, and 22% (P = 0.497) in groups A, B, and C, respectively. There were no significant differences among groups (P > 0.05). CONCLUSION: OH is helpful for diagnosis and treatment of abnormal intrauterine environment in women with a failed IVF cycle and further improves their pregnancy outcome in the following FET.

Effectiveness, safety and indications of acute normovolemic haemodilution in total knee arthroplasty.

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.

Prognostic value of RRM1 and its effect on chemoresistance in pancreatic cancer.

PURPOSE: Pancreatic cancer (PC) remains a lethal disease, and gemcitabine resistance is prevalent. However, the biomarkers suggestive of gemcitabine resistance remain unclear. METHODS: Bioinformatic tools identified ribonucleotide reductase catalytic subunit M1 (RRM1) in gemcitabine-related datasets. A cox regression model revealed the predictive value of RRM1 with clinical features. An external clinical cohort confirmed the prognostic value of RRM1. RRM1 expression was validated in gemcitabine-resistant cells in vitro and in orthotopic PC model. CCK8, flow cytometry, transwell migration, and invasion assays were used to explore the effect of RRM1 on gemcitabine-resistant cells. The CIBERSORT algorithm investigated the impact of RRM1 on immune infiltration. RESULTS: The constructed nomogram based on RRM1 effectively predicted prognosis and was further validated. Moreover, patients with higher RRM1 had shorter overall survival. RRM1 expression was significantly higher in PC tissue and gemcitabine-resistant cells in vitro and in vivo. RRM1 knockdown reversed gemcitabine resistance, inhibited migration and invasion. The infiltration levels of CD4 + T cells, CD8 + T cells, neutrophils, and plasma cells correlated markedly with RRM1 expression, and communication between tumor and immune cells probably depends on NF-κB/mTOR signaling. CONCLUSION: RRM1 may be a potential marker for prognosis and a target marker for gemcitabine resistance in PC.

Cirsiliol induces autophagy and mitochondrial apoptosis through the AKT/FOXO1 axis and influences methotrexate resistance in osteosarcoma.

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.

Heteroplasmy and Individual Mitogene Pools: Characteristics and Potential Roles in Ecological Studies.

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.

Characterization of two novel Fe(III)-reducing and electrogenic bacteria, Shewanella ferrihydritica sp. nov. and Shewanella electrica sp. nov., isolated from mangrove sediment.

Three novel strains in the genus Shewanella, designated A3AT, C31T and C32, were isolated from mangrove sediment samples. They were facultative anaerobic, Gram-stain-negative, rod-shaped, flagellum-harbouring, oxidase- and catalase-positive, electrogenic and capable of using Fe(III) as an electron acceptor during anaerobic growth. Results of phylogenetic analysis based on 16S rRNA gene and genomic sequences revealed that the strains should be assigned to the genus Shewanella. The 16S rRNA gene similarity, average nucleotide identity (ANI) and digital DNA-DNA hybridization (dDDH) values between the isolates and their closely related species were below the respective cut-off values for species differentiation. The 16S rRNA gene similarity, ANI and dDDH values between strains C31T and C32 were 99.7, 99.9 and 99.9 %, respectively, indicating that they should belong to the same genospecies. Based on polyphasic taxonomic approach, two novel species are proposed, Shewanella ferrihydritica sp. nov. with type strain A3AT (GDMCC 1.2732T=JCM 34899T) and Shewanella electrica sp. nov. with type strain C31T (GDMCC 1.2736T=JCM 34902T).

Relation between iodine nutrition and thyroid diseases in Qinghai, China.

Objective: To 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. Methods: Using 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. Results: 1. 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%) (P<0.05). 5. There was no statistical significance in the detection rates of clinical hyperthyroidism, subclinical hypothyroidism, subclinical hypothyroidism, goiter, thyroid nodules, TPO Ab and TG Ab positive rates in different iodine nutritional status (P>0.05). The positive rate of hypothyroidism in the iodine deficiency group is higher than in other iodine nutrition groups. Conclusion: The 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).

Comprehensive analysis on subchondral bone marrow lesions of human osteoarthritis by integrating bulk and single-cell transcriptomes.

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.

Anatomic characteristics of shoulder based on MRI accurately predict incomplete rotator cuff injuries in patients: relevance for predictive, preventive, and personalized healthcare strategies.

Background and PPPM-related working hypothesis: In the diagnosis of incomplete rotator cuff injuries (IRCI), magnetic resonance imaging (MRI) and ultrasound examination often have false-positive and false-negative results, while arthroscopy is expensive, invasive, and complex. From the strategy of predictive, preventive, and personalized medicine (PPPM), shoulder anatomical characteristics based on MRI have been demonstrated to accurately predict IRCI and their clinical applicability for personalized prediction of IRCI. Aims: This study aimed to develop and validate a nomogram based on anatomical features of the shoulder on MRI to identify IRCI for PPPM healthcare strategies. Methods: The medical information of 257 patients undergoing preoperative MRI examination was retrospectively reviewed and served as the primary cohort. Partial-thickness rotator cuff tears (RCTs) and tendinopathy observed under arthroscopy were considered IRCI. Using logistic regression analyses and least absolute shrinkage and selection operator (LASSO), IRCI was identified among various preoperative factors containing shoulder MRI and clinical features. A nomogram was constructed and subjected to internal and external validations (80 patients). Results: The following eight independent risk factors for IRCI were identified:AgeThe left injured sidesThe Goutallier classification of supraspinatus in oblique coronal positionThe Goutallier classification of supraspinatus in the axial positionAcromial thicknessAcromiohumeral distanceCoracohumeral distanceAbnormal acromioclavicular joint signalsThe nomogram accurately predicted IRCI in the development (C-index, 0.932 (95% CI, 0.891, 0.973)) and validation (C-index, 0.955 (95% CI, 0.918, 0.992)) cohorts. The calibration curve was consistent between the predicted IRCI probability and the actual IRCI ratio of the nomogram. The decision curve analysis and clinical impact curves demonstrated that the model had high clinical applicability. Conclusions: Eight independent factors that accurately predicted IRCI were determined using MRI anatomical findings. These personalized factors can prevent unnecessary diagnostic interventions (e.g., arthroscopy) and can assist surgeons in implementing individualized clinical decisions in medical practice, thus addressing the goals of PPPM. Supplementary Information: The online version contains supplementary material available at 10.1007/s13167-023-00333-5.

Ribosomal DNA copy number alteration in blood sample from gastric cancer patients.

BACKGROUND: Ribosomal DNA (rDNA) is the most abundant and important housekeeping gene in the cell. It usually acted as DNA damage sensor in DNA damage reaction. Gastric cancer (GC) as a tumor with high morbidity and mortality, it is hard to diagnosis in an early stage. METHODS: In this study, we collected and test the copy number of rDNA in blood sample of 42 GC patients and 56 healthy controls (HC) to explore the relationship between rDNA and GC. Besides, we make a correlation between the copy number of rDNA and ten biomarkers (CYFR21-1, CA15-3, CA72-4, NSE, CEA, CA125, ProGRP, AFP, SCC, CA19-9). RESULTS: The copy number of 18 S, 5.8 S, 28 S rDNA in GC is less than HC and 5 S is more than HC in their blood sample. And the expression of H-cox-1 and ND1 in GC is higher than HC in blood sample. it shows the expression of CA15-3 is related to ND1 and H-cox-1. CONCLUSION: We found for the first time the changes of rDNA and mtDNA expression in the blood of patients with gastric cancer. All these finding suggests rDNA may have potential in diagnosing GC.

Cancer-specific survival in patients with cholangiocarcinoma after radical surgery: a Novel, dynamic nomogram based on clinicopathological features and serum markers.

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 < 0.001) lower than the nomogram's C-indices (0.84, 0.77, and 0.74 in the training, internal and external validation cohorts respectively). CONCLUSIONS: A realistic and useful model for clinical decision-making and the optimization of therapy is presented as a nomogram that includes serum markers and clinicopathologic features for predicting postoperative survival in cholangiocarcinoma.

Risk factors for surgical site infection in patients with gastric cancer: A meta-analysis.

Surgical Site Infection (SSI) is one of the common postoperative complications after gastric cancer surgery. Previous studies have explored the risk factors (such as age, diabetes, anaemia and ASA score) for SSI in patients with gastric cancer. However, there are large differences in the research results, and the correlation coefficients of different research results are quite different. We aim to investigate the risk factors of surgical site infection in patients with gastric cancer. We queried four English databases (PubMed, Embase, Web of Science and the Cochrane Library) and four Chinese databases (China National Knowledge Infrastructure, Chinese Biological Medicine Database, Wanfang Database and Chinese Scientific Journal Database (VIP Database)) to identify published literature related to risk factors for surgical site infection in patients with gastric cancer. Rev Man 5.4 and Stata 15.0 were used in this meta-analysis. A total of 15 articles (n = 6206) were included in this analysis. The following risk factors were found to be significantly associated with surgical site infection in gastric cancer: male (OR = 1.28, 95% CI [1.06, 1.55]), age >60 (OR = 2.75, 95% CI [1.65, 4.57]), smoking (OR = 1.99, 95% CI [1.46, 2.73]), diabetes (OR = 2.03, 95% CI [1.59, 2.61]), anaemia (OR = 4.72, 95% CI [1.66, 13.40]), preoperative obstruction (OR = 3.07, 95% CI [1.80, 5.23]), TNM ≥ III (OR = 2.05, 95% CI [1.56, 2.70]), hypoproteinemia (OR = 3.05, 95% CI [2.08, 4.49]), operation time ≥3 h (OR = 8.33, 95% CI [3.81, 18.20]), laparotomy (OR = 2.18, 95% CI [1.61, 2.94]) and blood transfusion (OR = 1.44, 95% CI [1.01, 2.06]). This meta-analysis showed that male, age >60, smoking, diabetes, anaemia, preoperative obstruction, TNM ≥ III, hypoproteinemia, operation time ≥3 h, open surgery and blood transfusion were the risk factors for SSI in patients with gastric cancer.

Calcitriol-Loaded Multifunctional Nanospheres with Superlubricity for Advanced Osteoarthritis Treatment.

Osteoarthritis (OA) is characterized by the lubrication dysfunction of a cartilage sliding interface caused by chronic joint inflammation, and effective nonsurgical therapy for advanced OA remains lacking. Addressing chronic joint inflammation, lubrication dysfunction, and cartilage-tissue degradation simultaneously may hopefully tackle this challenge. Herein, we developed superlubricative zein@alginate/strontium@calcitriol (ZASC) nanospheres to treat advanced OA. ZASC was confirmed to significantly improve joint lubrication through traditional tribological tests and our proposed tribological experiment to mimic the intra-articular condition based on the human medial tibiofemoral joint tissues. This finding was attributed to the hydration lubrication formed around the alginate-strontium spheres that enabled ball-bearing lubrication and the filling of cartilage defects. Moreover, ZASCs that released calcitriol in a sustained manner showed proliferative, anti-inflammatory, and anti-apoptosis effects in vitro. Further experiments demonstrated that ZASC exerted chondroprotective effects by inhibiting the breakdown of the extracellular matrix in patient-derived OA cartilage explants. In vivo results demonstrated that ZASC can effectively maintain a normal gait to improve joint function, inhibit abnormal bone remodeling and cartilage degradation in early OA and can effectively reverse the advanced OA progression. Therefore, ZASC is a potentially nonsurgical therapeutic strategy for advanced OA treatments.

A model-based quantitative analysis of efficacy and associated factors of platelet rich plasma treatment for osteoarthritis.

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 sugges t 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.

Brief research report: Effects of Pinch deficiency on cartilage homeostasis in adult mice.

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.

Diffuse pigmented villonodular synovitis treated with arthroscopic total synovial peel.

BACKGROUND: Diffuse pigmented villonodular synovitis (PVNS) is prone to recurrence after surgery, and it is difficult to achieve a long-term complete cure. OBJECTIVE: To reduce the recurrence rate of PVNS, the author pioneered the arthroscopic total synovial peel (ATSP). METHODS: From March 2014 to July 2020, a total of 19 patients (6 males and 13 females) with diffuse PVNS of the knee were treated in our department and underwent ATSP. It's 'peel' rather than simple excision. This method is similar to peeling bark. Relapse rates and functional scores were determined, with follow-ups ranging from 12 to 72 months, on average 36 months. RESULTS: Treatment efficacy was assessed by imaging and functional scores. Imaging results indicated a recurrence rate of 10.5%. In patients without recurrence, the visual analog score (VAS) decreased from 4.76 ± 2.02 preoperatively to 1.56 ± 1.15 postoperatively. The Tegner-Lysholm knee function score (TLS) score increased from 67.76 ± 15.64 preoperatively to 90.32 ± 8.32 postoperatively. Compared with the literature, ATSP significantly reduces the postoperative recurrence rate of diffuse PVNS. The preliminarily findings suggest that this approach could greatly reduce the recurrence rate of postoperative PVNS in follow-up studies. CONCLUSION: This approach may be a viable option for treating diffuse PVNS via arthroscopy and is worthy of clinical consideration.