A Multimode Optical Sensor for Selective and Sensitive Detection of Harmful Heavy Metal Cr(VI) in Fresh Water and Sea Water.

Water pollution originating from heavy metals has shown great impacts on the ecological environment and human health due to their extremely low biodegradability. Hexavalent chromium Cr(VI), as one harmful heavy metal with strong oxidation, high biological permeability, and high carcinogenicity, is becoming an increasingly serious threat to human health. Therefore, conveniently but accurately, monitoring the Cr(VI) level in water to maintain its normal level and ensuring the stability of the ecosystem and human health become very valuable. However, most of these heavy metal sensors reported are turn-off type single-emission sensors. In this work, a ratiometric fluorescence/colorimetry/smartphone triple-mode turn-on optical sensor for Cr(VI) was developed based on a multifunctional metal-organic framework platform. The detection limits for these three mutual verification modes were only 1.28, 4.89, and 68.4 nM, respectively. Additionally, the color changes of the detection system under sunlight can also be observed directly by the naked eye. The accuracy and practicability of this multimode sensor were further proved by the detection of Cr(VI) in actual water and seawater samples, and the recovery rate ranged from 97.308 to 104.041%.

AKR1C3 in carcinomas: from multifaceted roles to therapeutic strategies.

Aldo-Keto Reductase Family 1 Member C3 (AKR1C3), also known as type 5 17ß-hydroxysteroid dehydrogenase (17ß-HSD5) or prostaglandin F (PGF) synthase, functions as a pivotal enzyme in androgen biosynthesis. It catalyzes the conversion of weak androgens, estrone (a weak estrogen), and PGD2 into potent androgens (testosterone and 5α-dihydrotestosterone), 17ß-estradiol (a potent estrogen), and 11ß-PGF2α, respectively. Elevated levels of AKR1C3 activate androgen receptor (AR) signaling pathway, contributing to tumor recurrence and imparting resistance to cancer therapies. The overexpression of AKR1C3 serves as an oncogenic factor, promoting carcinoma cell proliferation, invasion, and metastasis, and is correlated with unfavorable prognosis and overall survival in carcinoma patients. Inhibiting AKR1C3 has demonstrated potent efficacy in suppressing tumor progression and overcoming treatment resistance. As a result, the development and design of AKR1C3 inhibitors have garnered increasing interest among researchers, with significant progress witnessed in recent years. Novel AKR1C3 inhibitors, including natural products and analogues of existing drugs designed based on their structures and frameworks, continue to be discovered and developed in laboratories worldwide. The AKR1C3 enzyme has emerged as a key player in carcinoma progression and therapeutic resistance, posing challenges in cancer treatment. This review aims to provide a comprehensive analysis of AKR1C3's role in carcinoma development, its implications in therapeutic resistance, and recent advancements in the development of AKR1C3 inhibitors for tumor therapies.

Terpenoids derived from Semen Ziziphi Spinosae oil enhance sleep by modulating neurotransmitter signaling in mice.

Semen Ziziphi Spinosae oil (SZSO) is a natural vegetable oil extracted from Semen Ziziphi Spinosae, a traditional Chinese medicine renowned for its sleep-promoting properties, while the mechanisms are still unclear. Our findings revealed that the terpenoids present in SZSO (T-SZSO) were identified as the active components responsible for promoting sleep. Network pharmacological analysis suggested that T-SZSO targeted different sleep-aid pathways to varying degrees and exhibited potential for preventing central nervous system diseases. Notably, lupeol and betulinicaldehyde exhibited more pronounced effects. Additionally, T-SZSO significantly elevated serotonin levels, enhanced gamma-aminobutyric acid (GABA) synthesis, promoted GABA A receptor expression, and decreased glutamate and norepinephrine expression levels. Moreover, T-SZSO was found to downregulate IL-1ß expression while upregulating superoxide dismutase and inducible nitric oxide synthase levels. In conclusion, this study presents the first investigation into the pharmacological basis of SZSO in promoting sleep and highlights the potential of nature food in improving suboptimal health conditions.

TRPA1-PI3K/Akt-OPA1-ferroptosis axis in ozone-induced bronchial epithelial cell and lung injury.

BACKGROUND: Transient receptor potential (TRP) ankyrin 1 (TRPA1) could mediate ozone-induced lung injury. Optic Atrophy 1 (OPA1) is one of the significant mitochondrial fusion proteins. Impaired mitochondrial fusion, resulting in mitochondrial dysfunction and ferroptosis, may drive the onset and progression of lung injury. In this study, we examined whether TRPA1 mediated ozone-induced bronchial epithelial cell and lung injury by activating PI3K/Akt with the involvement of OPA1, leading to ferroptosis. METHODS: Wild-type, TRPA1-knockout (KO) mice (C57BL/6 J background) and ferrostatin-1 (Fer-1)-pretreated mice were exposed to 2.5 ppm ozone for 3 h. Human bronchial epithelial (BEAS-2B) cells were treated with 1 ppm ozone for 3 h in the presence of TRPA1 inhibitor A967079 or TRPA1-knockdown (KD) as well as pharmacological modulators of PI3K/Akt-OPA1-ferroptosis. Transcriptome was used to screen and decipher the differential gene expressions and pathways. Oxidative stress, inflammation and ferroptosis were measured together with mitochondrial morphology, function and dynamics. RESULTS: Acute ozone exposure induced airway inflammation and airway hyperresponsiveness (AHR), reduced mitochondrial fusion, and enhanced ferroptosis in mice. Similarly, acute ozone exposure induced inflammatory responses, altered redox responses, abnormal mitochondrial structure and function, reduced mitochondrial fusion and enhanced ferroptosis in BEAS-2B cells. There were increased mitochondrial fusion, reduced inflammatory responses, decreased redox responses and ferroptosis in ozone-exposed TRPA1-KO mice and Fer-1-pretreated ozone-exposed mice. A967079 and TRPA1-KD enhanced OPA1 and prevented ferroptosis through the PI3K/Akt pathway in BEAS-2B cells. These in vitro results were further confirmed in pharmacological modulator experiments. CONCLUSION: Exposure to ozone induces mitochondrial dysfunction in human bronchial epithelial cells and mouse lungs by activating TRPA1, which results in ferroptosis mediated via a PI3K/Akt/OPA1 axis. This supports a potential role of TRPA1 blockade in preventing the deleterious effects of ozone.

Existing hip joint disease is associated with an increased incidence of hip fracture in adults: A retrospective survey of 9710 individuals from a single center.

Objective: In hip disease patients, pain and movement restrictions might cause changes in bone strength and increase the likelihood of falls, finally leading to hip fracture. The aim of this study was to identify the incidence of, characteristics of and risk factors for hip fracture in patients with existing hip disease. Methods: This was a retrospective cohort study. Patients with existing hip disease treated at both outpatient and inpatient departments of our institute were identified by searching the electronic medical record system and followed retrospectively for the occurrence of hip fracture. Demographic and clinical characteristics, such as age, sex and kind of primary hip disease, were collected from the electronic medical record system. The incidence and timing of hip fracture were estimated, and a Cox regression model was built to identify the independent risk factors for hip fracture in these patients. Results: A total of 9710 eligible patients were included. After a mean follow-up of 3.97 years, hip fractures were identified in 95 patients, for an estimated incidence of hip fracture of 978.37 per 100,000 patients. The femoral neck was involved in 49 fractures (51.58 %), and the femoral trochanter was involved in 45 fractures (47.37 %). Four independent risk factors and one protective factor for hip fracture in patients with hip diseases were identified: age (HR = 1.116, 95 % CI = 1.094-1.138), the presence of osteonecrosis of the femoral head (HR = 2.201, 95 % CI = 1.217-3.980), a lower Harris hip score (HR = 0.966, 95 % CI = 0.949-0.982), a history of previous hip surgery (HR = 2.126, 95 % CI = 1.304-3.466) and the use of walking aids (HR = 0.588, 95 % CI = 0.354-0.975). A scoring system with a total score of 20 points was built, which included all of the above risk factors. The predictive scores for a low risk (estimated incidence of hip fracture ≤30 %), a moderate risk (estimated incidence of hip fracture 31 %-69 %), and a high risk (estimated incidence of hip fracture ≥70 %) of hip fracture were ≤8.5 points, 9.0-13.0 points and ≥13.5 points, respectively. Conclusion: The incidence of hip fracture in the special population of patients with existing hip disease was determined. Elderly patients, patients with a history of hip surgery, patients with osteonecrosis and patients with poor Harris hip scores were at increased risk of hip fracture. In patients with a predictive score greater than 9 points, indicating a moderate to high risk of hip fracture, the use of a walking aid might reduce the risk of hip fracture.

Role of mitochondrial fusion proteins MFN2 and OPA1 on lung cellular senescence in chronic obstructive pulmonary disease.

BACKGROUND: Mitochondrial dysfunction and lung cellular senescence are significant features involved in the pathogenesis of chronic obstructive pulmonary disease (COPD). Cigarette smoke (CS) stands as the primary contributing factor to COPD. This study examined mitochondrial dynamics, mitophagy and lung cellular senescence in COPD patients and investigated the effects of modulation of mitochondrial fusion [mitofusin2 (MFN2) and Optic atrophy 1 (OPA1)] on CS extract (CSE)-induced lung cellular senescence. METHODS: Senescence-associated secretory phenotype (SASP) component mRNAs (IL-1ß, IL-6, CXCL1 and CXCL8), mitochondrial morphology, mitophagy and mitochondria-related proteins (including phosphorylated-DRP1(p-DRP1), DRP1, MFF, MNF2, OPA1, PINK1, PARK2, SQSTM1/p62 and LC3b) and senescence-related proteins (including P16, H2A.X and Klotho) were measured in lung tissues or primary alveolar type II (ATII) cells of non-smokers, smokers and COPD patients. Alveolar epithelial (A549) cells were exposed to CSE with either pharmacologic inducer (leflunomide and BGP15) or genetic induction of MFN2 and OPA1 respectively. RESULTS: There were increases in mitochondrial number, and decreases in mitochondrial size and activity in lung tissues from COPD patients. SASP-related mRNAs, DRP1 phosphorylation, DRP1, MFF, PARK2, SQSTM1/p62, LC3B II/LC3B I, P16 and H2A.X protein levels were increased, while MFN2, OPA1, PINK1 and Klotho protein levels were decreased in lung tissues from COPD patients. Some similar results were identified in primary ATII cells of COPD patients. CSE induced increases in oxidative stress, SASP-related mRNAs, mitochondrial damage and dysfunction, mitophagy and cellular senescence in A549 cells, which were ameliorated by both pharmacological inducers and genetic overexpression of MFN2 and OPA1. CONCLUSIONS: Impaired mitochondrial fusion, enhanced mitophagy and lung cellular senescence are observed in the lung of COPD patients. Up-regulation of MFN2 and OPA1 attenuates oxidative stress, mitophagy and lung cellular senescence, offering potential innovative therapeutic targets for COPD therapy.

Femoral neck fracture patients with ischaemic stroke choose hemiarthroplasty or constrained liner total hip arthroplasty? A retrospective comparative study of 199 cases.

Background: The objective of this study was to assess the long-term survival rate, complications, as well as the clinical and radiological outcomes of hemiarthroplasty and total hip arthroplasty using constrained polyethylene liners in patients with ischemic stroke. Methods: This study was a retrospective cohort study that included patients with ischemic stroke who underwent hip arthroplasty from March 2010 to September 2017. In the Constrained Acetabular Liners (CAL) group, patients received an uncemented acetabular shell with a constrained polyethylene liner. The Dual Mobility (DM) group underwent hemiarthroplasty (HA). Additionally, hip function, range of motion, quality of life, the incidence of clinical complications, and prosthesis stability were investigated. Results: 96 patients with unilateral femoral neck fractures who underwent hip replacement with CAL were included in the CAL group, while 103 patients who underwent hip replacement with a dual mobility head were included in the DM group. VAS, and SF-36 data were available for both CAL and DM groups. At the 1-year postoperative follow-up, the HHS in the CAL group was significantly lower than that in the DM group (80.83 ± 3.91 vs. 83.17 ± 4.15, P < 0.05). The VAS score in the CAL group peaked at the 1-year follow-up (2.07 ± 0.91 vs. 1.49 ± 0.85, P < 0.05). However, there were no significant differences between the two groups in terms of HSS, VAS, and SF-36 at the last follow-up after surgery. Operative time and the amount of bleeding in the DM group were significantly lower than those in the CAL group (105.30 ± 29.68 vs. 94.85 ± 31.07; 355.11 ± 123.95 vs. 302.22 ± 107.68, P < 0.05). Additionally, there was no significant difference in the mean leg length discrepancy between the two groups. Conclusion: The clinical, imaging, and postoperative complications of the CAL and DM groups were analyzed. The prognosis for DM appears to be more beneficial for early patient recovery, but a higher likelihood of recurrent dislocation is observed. CAL offers excellent stability for primary THA in high-risk patients; however, attention should be given to preventing aseptic loosening.

Unleashing the efficacy of immune checkpoint inhibitors for advanced hepatocellular carcinoma: factors, strategies, and ongoing trials.

Hepatocellular carcinoma (HCC) is a prevalent primary liver cancer, representing approximately 85% of cases. The diagnosis is often made in the middle and late stages, necessitating systemic treatment as the primary therapeutic option. Despite sorafenib being the established standard of care for advanced HCC in the past decade, the efficacy of systemic therapy remains unsatisfactory, highlighting the need for novel treatment modalities. Recent breakthroughs in immunotherapy have shown promise in HCC treatment, particularly with immune checkpoint inhibitors (ICIs). However, the response rate to ICIs is currently limited to approximately 15%-20% of HCC patients. Recently, ICIs demonstrated greater efficacy in "hot" tumors, highlighting the urgency to devise more effective approaches to transform "cold" tumors into "hot" tumors, thereby enhancing the therapeutic potential of ICIs. This review presented an updated summary of the factors influencing the effectiveness of immunotherapy in HCC treatment, identified potential combination therapies that may improve patient response rates to ICIs, and offered an overview of ongoing clinical trials focusing on ICI-based combination therapy.

A new joint reconstruction technique in the treatment of giant cell tumors around the knee: Structural allograft and unicompartmental arthroplasty.

OBJECTIVE: The long-term prognosis of patients who underwent unicompartmental knee arthroplasty (UKA) with a structural allograft or hemiarticular allograft transplantation to treat giant cell tumors (GCTs) around the knee and the prosthesis survival rate were analyzed. METHODS: We retrospectively reviewed 73 patients who were diagnosed with GCTs around the knee and underwent surgery to restore joint function from 2000 to 2015. Patients were divided into two groups according to the surgical procedure used for functional knee reconstruction: hemiarticular allograft transplantation or structural allograft and UKA. The Knee Society Score (KSS) and Western Ontario and McMaster Universities Arthritis Index (WOMAC) were used to analyze postoperative knee function between the two groups. The Kellgren-Lawrence (K-L) classification system was used to evaluate the progression of osteoarthritis. The incidence of complications and the prosthesis survival rate were also investigated. RESULTS: Patients who underwent UKA to treat GCT demonstrated significantly improved knee function. The rate of an excellent or good KSS was significantly different between the two groups (p = 0.041 at the 1-year follow-up, p = 0.033 at the last follow-up). The proportion of severe cases according to WOMAC in the two groups was also different (p = 0.030 at the 1-year follow-up, p = 0.021 at the last follow-up). According to the K-L grade of unaffected compartments, UKA better prevented the progression of osteoarthritis (p = 0.034). CONCLUSIONS: Patients with GCTs around the knee could benefit from UKA. In addition to providing better knee function and range of motion, UKA could also slow the progression of osteoarthritis in the knee joint. This new surgical method could meet the needs of patients wishing to preserve joint integrity and favorable joint function.

Attenuation of PM2.5-induced alveolar epithelial cells and lung injury through regulation of mitochondrial fission and fusion.

BACKGROUND: Exposure to particulate matter (PM) with an aerodynamic diameter less than 2.5 µm (PM2.5) is a risk factor for developing pulmonary diseases and the worsening of ongoing disease. Mitochondrial fission and fusion are essential processes underlying mitochondrial homeostasis in health and disease. We examined the role of mitochondrial fission and fusion in PM2.5-induced alveolar epithelial cell damage and lung injury. Key genes in these processes include dystrophin-related protein 1 (DRP1) and optic atrophy 1 (OPA1) respectively. METHODS: Alveolar epithelial (A549) cells were treated with PM2.5 (32 µg/ml) in the presence and absence of Mdivi-1 (10µM, a DRP1 inhibitor) or BGP-15 (10µM, an OPA1 activator). Results were validated using DRP1-knockdown (KD) and OPA1-overexpression (OE). Mice were injected intraperitoneally with Mdivi-1 (20 mg/kg), BGP-15 (20 mg/kg) or distilled water (control) one hour before intranasal instillation of PM2.5 (7.8 mg/kg) or distilled water for two consecutive days. RESULTS: PM2.5 exposure of A549 cells caused oxidative stress, enhanced inflammation, necroptosis, mitophagy and mitochondrial dysfunction indicated by abnormal mitochondrial morphology, decreased mitochondrial membrane potential (ΔΨm), reduced mitochondrial respiration and disrupted mitochondrial fission and fusion. Regulating mitochondrial fission and fusion pharmacologically using Mdivi-1 and BGP-15 and genetically using DRP1-KD and OPA1-OE prevented PM2.5-induced celluar damage in A549 cells. Mdivi-1 and BGP-15 attenuated PM2.5-induced acute lung injury in mice. CONCLUSION: Increased mitochondrial fission and decreased mitochondrial fusion may underlie PM2.5-induced alveolar epithelial cell damage in vitro and lung injury in vivo.

Changes in targeted metabolomics in lung tissue of chronic obstructive pulmonary disease.

Background: Chronic obstructive pulmonary disease (COPD) is a common chronic lung disease and its incidence is steadily increasing. COPD patients and mouse models of COPD share some similarities in lung pathology and physiology. We performed this study to explore the potential metabolic pathways involved in the pathogenesis of COPD and to discover the COPD-associated biomarkers. Furthermore, we aimed to examine how much the mouse model of COPD was similar and different to human COPD in terms of the altered metabolites and pathways. Methods: Twenty human lung tissue samples (ten COPD and ten controls) and twelve mice lung tissue samples (six COPD and six controls) were analyzed by targeted HM350 metabolomics, and multivariate and pathway analysis were performed by Kyoto Encyclopedia of Genes and Genomes (KEGG) database. Results: The counts of many metabolites such as amino acids, carbohydrates and carnitines were changed in both COPD patients and mice compared to controls, respectively. While lipid metabolism was changed only in COPD mice. After KEGG analysis, we found these altered metabolites involved in COPD through aging, apoptosis, oxidative stress and inflammation pathways. Conclusions: The expressions of metabolites changed in both COPD patients and cigarette smoke exposed (CS-exposed) mice. And there were also some differences between COPD patients and mouse models due to the differences between species. Our study suggested the dysregulation in amino acid metabolism, energy production pathway and perhaps lipid metabolism may be significantly related to the pathogenesis of COPD.

The role of 3-dimensional preoperative planning for primary total hip arthroplasty based on artificial intelligence technology to different surgeons: A retrospective cohort study.

Preoperative planning with computed tomography (CT)-based 3-dimensiona (3D) templating has been achieved precise placement of hip components. This study investigated the role of the software (3-dimensional preoperative planning for primary total hip arthroplasty [THA] based on artificial intelligence technology, artificial intelligence hip [AIHIP]) for surgeons with different experience levels in primary THA. In this retrospective cohort study, we included patients, who had undergone THA with the help of the AIHIP, and matched to patients, who had undergone THA without the help of the AIHIP, by age and the doctor who operated on them. The subjects were divided into 4 groups, senior surgeon (Chief of Surgery) with AIHIP group, senior surgeon without AIHIP group, junior surgeon (Associate Chief of Surgery) with AIHIP group and junior surgeon without AIHIP group. The general data, imaging index, clinical outcomes and accuracy of stem size prediction and cup size prediction were retrospectively documented for all patients. There was a significant difference in discrepancy in leg length (P = .010), neck-shaft angle (P = .025) and femoral offset (P = .031) between the healthy side and the affected side, operation duration (P < .001), decrease in hemoglobin (Hb) per 24 hours (P = .046), intraoperative radiation exposure frequency (P < .050) and postoperative complications (overall P = .035) among the patients in junior surgeon group. No significant differences were found between senior surgeon groups with respect to discrepancy in leg length (P = .793), neck-shaft angle (P = .088)and femoral offset (P = .946) between the healthy side and the affected side, operation duration (P = .085), decrease in Hb per 24 hours (P = .952), intraoperative radiation exposure frequency (P = .094) and postoperative complications (overall P = .378). The stem sizes of 95% were accurately estimated to be within 1 stem size, and 97% of the cup size estimates were accurate to within 1 cup size in senior surgeon group with AIHIP. A total of 87% stem sizes were accurately estimated to be within 1 stem size, and 85% cup sizes were accurate to within 1 cup size in junior surgeon group with AIHIP. In conclusion, our study suggests that an AI-based preoperative 3D planning system for THA is a valuable adjunctive tool for junior doctor and should routinely be performed preoperatively.

Risk factors affecting the incidence of postoperative periprosthetic femoral fracture in primary hip arthroplasty patients: a retrospective study.

The purpose of this study was to identify the characteristics and risk factors for postoperative periprosthetic femoral fracture (PFF). This was a retrospective cohort study of 108 patients with and 432 control patients without postoperative PFF. Demographic characteristics, surgery-related information (primary hip disease diagnosed, fixation, femoral stem, method of operation, and bone resorption of the proximal femur), and postoperative patient outcomes (hip function, treatment history, and patients' lifestyle behaviors) were recorded and compared between the groups. PFF characteristics, such as the classification, time, and cause, were also documented, and a Cox regression model was built to identify the independent risk factors for postoperative PFF in these patients. Six independent risk factors for postoperative PFF were identified, namely, advanced age (hazard ratio (HR) = 1.026, 95% confidence interval (CI) = 1.007-1.045), femoral neck fracture as the primary disease (HR = 4.536, 95% CI = 2.955-6.961), osteoporosis (HR = 2.043, 95% CI = 1.234-3.383), hemiarthroplasty (or HA, HR = 2.173, 95% CI = 1.327-3.558), bone resorption of the proximal femur (HR = 1.627, 95% CI = 1.090-2.430), and a standard- or long-stem femoral prosthesis (HR = 2.996, 95% CI = 1.480-6.067). The predictive values for a low risk (estimated incidence ≤ 50%), moderate risk (estimated incidence 51%-89%), and high risk (estimated incidence ≥ 90%) of PFF were ≤ 3.0 points, 3.0-10.0 points, and ≥ 10.0 points, respectively. Most patients with postoperative PFF had Vancouver type B fractures. Six independent risk factors for postoperative PFF were identified: advanced age, hip fracture as the primary disease, osteoporosis, HA, bone resorption of the proximal femur, and a long femoral stem.

Effects of Anterior Pituitary Adenomas' Hormones on Glucose Metabolism and Its Clinical Implications.

Pituitary adenomas have recently become more common and their incidence is increasing yearly. Functional pituitary tumors commonly secrete prolactin, growth hormones, and adrenocorticotropic hormones, which cause diseases such as prolactinoma, acromegaly, and Cushing's disease, but rarely secrete luteinizing, follicle-stimulating, thyroid-stimulating, and melanocyte-stimulating hormones. In addition to the typical clinical manifestations of functional pituitary tumors caused by excessive hormone levels, some pituitary tumors are also accompanied by abnormal glucose metabolism. The effects of these seven hormones on glucose metabolism are important for the treatment of diabetes secondary to pituitary tumors. This review focuses on the effects of hormones on glucose metabolism, providing important clues for the diagnosis and treatment of related diseases.

Bone Remodelling of the Proximal Femur After Hip Revision with a Metaphyseal-Fixation Femoral Stem Component.

Background: Whether hip revision with a metaphyseal-fixation femoral stem component can restore the bone mass of the proximal femur remains unclear. The aims of this study were to identify whether the bone mineral density (BMD) of the proximal femur increases following hip revision with a metaphyseal-fixation femoral stem and to identify the factors associated with BMD recovery. Methods: This was a retrospective study involving 36 patients who underwent hip arthroplasty with a metaphyseal-diaphyseal fixation stem (standard length stem) and had indications for hip revision, which was performed with a proximal press-fit short-stem prosthesis for each patient. Dual-energy X-ray absorptiometry (DEXA) was used to obtain, evaluate, and compare the BMD at baseline and one year and two years postoperatively. The proximal femur was divided into several independent areas according to the Gruen zone (Gruen 1 to Gruen 7 from the greater trochanter counterclockwise to the lesser trochanter). Logistic regression analyses were used to assess potential factors significantly associated with an increase in BMD. Results: An increased BMD was obviously identified in the proximal femur. Two years after the surgery, the BMD of the Gruen 1, Gruen 2, Gruen 6, and Gruen 7 areas had increased by 22.6%, 12.6%, 16.2% and 24.2%, respectively, relative to baseline. Three independent risk factors associated with bone mineral density recovery were identified: age (OR=1.100, 95% CI=1.005-1.203, P=0.038), osteoporosis (OR=14.921, 95% CI=1.223-182.101, P=0.034) and fair to poor hip function (OR=13.142, 95% CI=1.024-168.582, P=0.048). Conclusion: This study confirms that metaphyseal-fixation stem hip revision can indeed help restore bone mass in the proximal femur, especially in the Gruen 1, Gruen 2, Gruen 6 and Gruen 7 zones. It was also found that advanced age, osteoporosis, and fair to poor hip joint function were three important risk factors affecting the recovery of proximal femur bone mass after surgery. Trial Registration: Retrospectively registered.

Comparison of minimally-invasive fibular supporting of T-type with traditional bloody iliac flap metastasis for osteonecrosis of the femoral head at ARCO stage II.

Purpose: Our research mainly evaluates the clinical efficacy of two surgical methods in the treatment of osteonecrosis of the femoral head (ONFH) at ARCO stage II, aiming to provide optimal hip-preserving treatment of ONFH. Method: From October 2018 to September 2020, 48 patients (59 hips) met the inclusion criteria and randomized. 24 cases (29 hips) in experimental group were treated with minimally-invasive fibular supporting of T-type; 24 cases (30 hips) in control group were treated with traditional bloody iliac flap metastasis. We will compare some intraoperative and postoperative conditions. Result: The operation time in experimental group was 37 (6) minutes, in control group was 130 (21.75) minutes; the length of surgical incision in two groups was 3.7 (0.7) cm and 12.85 (2.68) cm. The intraoperative blood loss in two groups was 69 (21) ml and 363 (87) ml; the postoperative VAS score of the experimental group on day 1, day 3, day 7 after surgery was 5.5 (2), 3.5 (1), 0 (1); the control group was 6 (1.75), 4 (1), 3 (1). The data differences between above groups have statistically significant. The follow-up time of two groups was (33.86 ± 5.66) months and (35.67 ± 4.69) months. The bone graft healing time in two groups was (14.21 ± 1.93) months and (13.83 ± 2.34) months. The Harris hip scores of two groups at the last follow-up were 90 (7.5) and 86.5 (8.5). The survival rates of two groups were 79.31% (23/29) and 76.67% (23/30). The difference was no statistically significant in above groups (P > 0.05). Conclusion: The two different bone graft implantation showed satisfactory early outcomes. Compared to the control group, the experimental group has the advantages of lesser pain, lesser blood loss, lesser trauma and shorter operation time. It may be a choice as bone graft for the treatment of ONFH at early stage.

Therapeutic potential of vasoactive intestinal peptide and its receptor VPAC2 in type 2 diabetes.

Owing to the increasing prevalence of type 2 diabetes, the development of novel hypoglycemic drugs has become a research hotspot, with the ultimate goal of developing therapeutic drugs that stimulate glucose-induced insulin secretion without inducing hypoglycemia. Vasoactive intestinal peptide (VIP), a 28-amino-acid peptide, can stimulate glucose-dependent insulin secretion, particularly by binding to VPAC2 receptors. VIP also promotes islet ß-cell proliferation through the forkhead box M1 pathway, but the specific molecular mechanism remains to be studied. The clinical application of VIP is limited because of its short half-life and wide distribution in the human body. Based on the binding properties of VIP and VPAC2 receptors, VPAC2-selective agonists have been developed to serve as novel hypoglycemic drugs. This review summarizes the physiological significance of VIP in glucose homeostasis and the potential therapeutic value of VPAC2-selective agonists in type 2 diabetes.

Bazi Bushen capsule attenuates cognitive deficits by inhibiting microglia activation and cellular senescence.

CONTEXT: Bazi Bushen capsule (BZBS) has anti-ageing properties and is effective in enhancing memory. OBJECTIVE: To find evidence supporting the mechanisms and biomarkers by which BZBS functions. MATERIALS AND METHODS: Male C57BL/6J mice were randomly divided into five groups: normal, ageing, ß-nicotinamide mononucleotide capsule (NMN), BZBS low-dose (LD-BZ) and BZBS high-dose (HD-BZ). The last four groups were subcutaneously injected with d-galactose (d-gal, 100 mg/kg/d) to induce the ageing process. At the same time, the LD-BZ, HD-BZ and NMN groups were intragastrically injected with BZBS (1 and 2 g/kg/d) and NMN (100 mg/kg/d) for treatment, respectively. After 60 days, the changes in overall ageing status, brain neuron morphology, expression of p16INK4a, proliferating cell nuclear antigen (PCNA), ionized calcium-binding adapter molecule 1 (Iba1), postsynaptic density protein 95 (PSD95), CD11b, Arg1, CD206, Trem2, Ym1 and Fizz1, and the senescence-associated secretory phenotype (SASP) factors were observed. RESULTS: Compared with the mice in the ageing group, the HD-BZ mice exhibited obvious improvements in strength, endurance, motor coordination, cognitive function and neuron injury. The results showed a decrease in p16INK4a, Iba1 and the upregulation of PCNA, PSD95 among brain proteins. The brain mRNA exhibited downregulation of Iba1 (p < 0.001), CD11b (p < 0.001), and upregulation of Arg1 (p < 0.01), CD206 (p < 0.05), Trem2 (p < 0.001), Ym1 (p < 0.01), Fizz1 (p < 0.05) and PSD95 (p < 0.01), as well as improvement of SASP factors. CONCLUSIONS: BZBS improves cognitive deficits via inhibition of cellular senescence and microglia activation. This study provides experimental evidence for the wide application of BZBS in clinical practice for cognitive deficits.

Direct separation and enumeration of CTCs in viscous blood based on co-flow microchannel with tunable shear rate: a proof-of-principle study.

Circulating tumor cells (CTCs), which have extremely low density in whole blood, are an important indicator of primary tumor metastasis. Isolation and enumeration of these cells are critical for clinical applications. Separation of CTCs from massive blood cells without labeling and addition of synthetic polymers is challenging. Herein, a novel well-defined co-flow microfluidic device is presented and used to separate CTCs in viscous blood by applying both inertial and viscoelastic forces. Diluted blood without any synthetic polymer and buffer solution were used as viscoelastic fluid and Newtonian fluid, respectively, and they were co-flowed in the designed chip to form a sheath flow. The co-flow system provides the function of particle pre-focusing and creates a tunable shear rate region at the interface to adjust the migration of particles or cells from the sample solution to the buffer solution. Successful separation of CTCs from viscous blood was demonstrated and enumeration was also conducted by image recognition after separation. The statistical results indicated that a recovery rate of cancer cells greater than 87% was obtained using the developed method, which proved that the direct separation of CTCs from diluted blood can be achieved without the addition of any synthetic polymer to prepare viscoelastic fluid. This method holds great promise for the separation of cells in viscous biological fluid without either complicated channel structures or the addition of synthetic polymers.

Retrospective Study from a Single Center to Identify Risk Factors Associated with Reinfection in Patients Undergoing 2-Stage Revision Surgery for Periprosthetic Joint Infection.

BACKGROUND This study identified risk factors associated with reinfection and created a scoring system designed for patients with periprosthetic joint infection (PJI) who have undergone prosthetic resection and spacer implantation. MATERIAL AND METHODS Patients who underwent 2-stage revision for PJI from January 2010 to December 2017 were retrospectively analyzed in this study. Patients were divided into 2 groups: infection recurrence and infection cure. Demographic and clinical information, laboratory test results, and radiological images that were potentially associated with infection were obtained and analyzed. RESULTS Seven independent risk (protective) factors for infection recurrence in patients with PJI who underwent 2-stage hip revision surgery were identified: C-reactive protein level, type of bacterial infection, age, immunosuppression, albumin/globulin ratio, glucose level, and magnetic resonance imaging findings. Finally, a weighted scoring system of 100-mark system was established and the area under the curve was 0.965 (95% confidential interval=0.947-0.983). The predictive scores for low risk (≤30%), moderate risk (31-69%), and high risk (≥70%) of infection recurrence were ≤45, 46-77, and ≥78, respectively. CONCLUSIONS For patients with PJI who had already undergone joint resection and spacer implantation, this newly established scoring system might help determine the accurate risk of infection recurrence after a definitive new prosthesis implantation. Patients with scores greater than 78 points would be considered very likely to have an infection recurrence. Therefore, the second-stage revision surgery should be changed to an additional anti-infection treatment or a debridement surgery instead of a definitive prosthesis implantation surgery.