A new dressing system for accelerating wound recovery after primary total knee arthroplasty: a feasibility study.

PURPOSE: Currently, postoperative wound infection and poor healing of total knee arthroplasty have been perplexing both doctors and patients. We hereby innovatively invented a new dressing system to reduce the incidence of postoperative wound complications. METHODS: We enrolled 100 patients who received primary unilateral total knee arthroplasty and then applied the new dressing system. The data collected included the number of dressing changes, postoperative hospital stay, Visual Analogue Scale score (VAS), the Knee Society Score (KSS), the Knee Injury and Osteoarthritis Outcome Score (KOOS), ASEPSIS scores, The Stony Brook Scar Evaluation Scale (SBSES), wound complications, dressing cost, the frequency of shower and satisfaction. Subsequently, a statistical analysis of the data was performed. RESULTS: Our findings demonstrated the average number of postoperative dressing changes was 1.09 ± 0.38, and the average postoperative hospital stay was 3.72 ± 0.98 days. The average cost throughout a treatment cycle was 68.97 ± 12.54 US dollars. Collectively, the results of VAS, KSS, and KOOS revealed that the pain and function of patients were continuously improved. The results of the four indexes of the ASEPSIS score were 0, whereas the SBSES score was 3.58 ± 0.52 and 4.69 ± 0.46 at two weeks and one month after the operation, respectively. We observed no wound complications until one month after the operation. Remarkably, the satisfaction rate of the patients was 91.85 ± 4.99% one month after the operation. CONCLUSION: In this study, we invented a new dressing system for surgical wounds after total knee arthroplasty and further confirmed its clinical feasibility and safety. CHINESE CLINICAL TRIAL REGISTRY: ChiCTR2000033814, Registered 13/ June/2020.

EGCG suppresses PD-1 expression of T cells via inhibiting NF-κB phosphorylation and nuclear translocation.

Epigallocatechin-3-gallate (EGCG) is an important tea polyphenol with anti-tumor potential. Our previous studies revealed that EGCG was a promising immune checkpoint inhibitor (ICI) as it could downregulate expression of programmed cell death 1 ligand 1 (PD-L1) in tumor cells, thereby resulting tumor killing effect. In particular, EGCG can effectively avoid the inflammatory storm caused by anti-tumor therapy, which is a healthy green capacity absent from many ICIs. However, the relationship between EGCG and programmed cell death 1 (PD-1) of T cells remains unclear. In this work, we explored the effect of EGCG on T cells and found that EGCG suppressed PD-1 via inhibiting NF-κB phosphorylation and nuclear translocation. Furtherly, the capability of EGCG was confirmed in tumor-bearing mice to inhibit PD-1 expression in T cells and enhance apoptosis in tumor cells. These results implied that EGCG could inhibit the expression of PD-1 in T cells, thereby promoting anti-tumor effects of T cells. EGCG will be a promising candidate in anti-tumor therapy.

The value of audiovisual sexual stimulation with virtual reality in diagnosing erectile dysfunction.

Background: The traditional audiovisual sexual stimulation (AVSS) test may experience limitations including low erectile response rate and lack of unified diagnostic criteria. Aim: We aimed to explore the clinical value of AVSS with virtual reality (VR-AVSS) test in assessing erectile function and diagnosing erectile dysfunction (ED). Methods: Participants 18 to 60 years of age were screened for analysis in 3 clinical centers from June 2020 to March 2022. Demographic data, 5-item International Index of Erectile Function (IIEF-5), erectile hardness score (EHS), and self-reported symptom questions were collected. The ED patients and control patients were confirmed according to the IIEF-5 and EHS. All subjects watched a 60-minute erotic video by VR device during RigiScan recording. The parameters including tip average rigidity, tip effective erectile duration (duration of rigidity ≥60%, tip effective erectile duration), base average rigidity, and base effective erectile duration were evaluated. Outcomes: The main outcome of interest was the application of VR immersion technology to improve the traditional AVSS test. Results: A total of 301 ED cases and 100 eligible control patients were included for final analysis. Compared with control patients, ED cases had significantly lower IIEF-5 scores, EHS, positive response rate, and erectile rigidity and duration. The positive response rate of ED and control patients were 75.5% and 90.9%, respectively. The cutoff points of tip average rigidity, tip effective erectile duration, base average rigidity, and base effective erectile duration were 40.5% (sensitivity: 77.6%, specificity: 70.2%; P < .001), 4.75 minutes (sensitivity: 75.9%, specificity: 75.4%; P < .001), 48.5% (sensitivity: 77.6%, specificity: 75.1%; P < .001), and 7.75 minutes (sensitivity: 79.3%, specificity: 75.7%; P < .001). Clinical Implications: The technological superiority of VR will enable the VR-AVSS immersion test to be a more accurate detection than traditional AVSS modes. Strengths and Limitations: Our study applied VR immersion technology to establish the standard operation procedure for the AVSS test, which could effectively reduce the interference of adverse factors and minimize the detecting errors. However, the test data only included positive response subjects, so the true erectile status of men with a negative response to the AVSS test cannot be obtained. Conclusions: The VR-AVSS test can effectively improve the diagnostic accuracy of ED. The average rigidity and effective erectile duration were the optimal diagnostic parameters for excluding ED.

Impact of delayed diagnosis and treatment on tuberculosis infection within families: A case report.

BACKGROUND: A 32-year-old male patient was diagnosed with a 30% left pneumothorax on November 5, 2020, during which chest imaging indicated abnormalities. Despite this, pulmonary tuberculosis (TB) was not diagnosed or treated at that time due to a negative result in the MGIT960 culture. The patient experienced symptoms of cough and expectoration on April 24, 2022. Upon repeating the chest imaging, the condition had worsened, confirming the presence of pulmonary TB, leading to the patient's hospitalization. On September 1, 2022, the 11-year-old daughter of the patient was diagnosed with pulmonary tuberculosis accompanied by bronchial tuberculosis and tuberculous pleurisy. METHODS: The diagnosis of pulmonary tuberculosis was confirmed through sputum smears and Gene Xpert MTB/RIF testing, for the patient and his 11-year-old daughter in 2022. The patient underwent a 6-month combination therapy (2HRZE/4HR) comprising isoniazid, rifampicin, pyrazinamide, and ethambutol. His daughter with pulmonary tuberculosis accompanied by bronchial tuberculosis and tuberculous pleurisy underwent a 12-month combination therapy. RESULTS: Late diagnosis and treatment delays contribute to tuberculosis infections within families. Fortunately, after more than 3 months of antituberculosis treatment, the patient experienced relief from cough and sputum secretion, and there was improvement observed in the chest CT scan. Six months later, the patient was successfully cured of TB. 12 months later, his daughter also was successfully cured of TB. CONCLUSION SUBSECTIONS: Early diagnosis and treatment of tuberculosis (TB) is vital to reduce transmission, morbidity, and mortality.

Polarity-Mediated Antisolvent Control Enables Efficient Lanthanide-Based near-Infrared Perovskite LEDs.

Alloying lanthanide ions (Yb3+) into perovskite quantum dots (Yb3+:CsPb(Cl1-xBrx)3) is an effective method to achieve efficient near-infrared (NIR) luminescence (>950 nm). Increasing the Yb3+ alloying ratio in the perovskite matrix enhances the luminescence intensity of Yb3+ emission at 990 nm. However, high Yb3+ alloying (>15%) results in vacancy-induced inferior material stability. In this work, we developed a polarity-mediated antisolvent manipulation strategy to resolve the incompatibility between a high Yb3+ alloying ratio and inferior stability of Yb3+:CsPb(Cl1-xBrx)3. Precise control of solution polarity enables increased uniformity of the perovskite matrix with fewer trap densities. Employing this strategy, we obtain Yb3+:CsPb(Cl1-xBrx)3 with the highest Yb3+ alloying ratio of 30.2% and a 2-fold higher electroluminescence intensity at 990 nm. We lever the engineered Yb3+:CsPb(Cl1-xBrx)3 to fabricate NIR-LEDs, achieving a peak external quantum efficiency (EQE) of 8.5% at 990 nm: this represents the highest among perovskite NIR-LEDs with an emission wavelength above 950 nm.

Voltage-Mode Ferroelectric Synapse for Neuromorphic Computing.

Ferroelectric materials with a modulable polarization extent hold promise for exploring voltage-driven neuromorphic hardware, in which direct current flow can be minimized. Utilizing a single active layer of an insulating ferroelectric polymer, we developed a voltage-mode ferroelectric synapse that can continuously and reversibly update its states. The device states are straightforwardly manifested in the form of variable output voltage, enabling large-scale direct cascading of multiple ferroelectric synapses to build a deep physical neural network. Such a neural network based on potential superposition rather than current flow is analogous to the biological counterpart driven by action potentials in the brain. A high accuracy of over 97% for the simulation of handwritten digit recognition is achieved using the voltage-mode neural network. The controlled ferroelectric polarization, revealed by piezoresponse force microscopy, turns out to be responsible for the synaptic weight updates in the ferroelectric synapses. The present work demonstrates an alternative strategy for the design and construction of emerging artificial neural networks.

Rapid authentication of variants of Gastrodia elata Blume using near-infrared spectroscopy combined with chemometric methods.

The variety is one of the most important factors to generate difference of chemical compositions, which unavoidably influences the quality of natural medicine. Thus, simple and rapid authentication of different variants has great academic and practical significance. In this study, the goal was achieved with the help of near infrared spectroscopy (NIR) and chemometrics by using Gastrodia elata Blume as an example. A total of 540 samples including two classes of variants and their forms were investigated as a whole. The mean spectra of samples of each class and their 2-D synchronous correlation spectra were simultaneously applied to discover the difference of chemical characteristics. After hybrid pre-processing of the first and second derivative combined with Savitzky-Golay and Norris filtering, partial least squares discrimination analysis (PLS-DA) on the basis of latent variable projection was used to assess the feasibility for classification. The results show higher prediction accuracy in both internal test set and external prediction set. In order to further improve the robustness for modeling, three methods for wavelength selection were comprehensively compared to optimize PLS-DA models, including variable importance in the projection (VIP), random frog (RF), and Monte Carlo uninformative variable elimination (MC-UVE). The prediction accuracy of combination of the 2nd derivative, Norris, MC-UVE and PLS-DA achieved to 99.11% and 98.89% corresponding to the internal test set and external prediction set, respectively. The strategies proposed in this work perform effectiveness for rapid and accurate authentication of variants of plants with high chemical complexity.

Analysis of factors influencing patient delay by patients with pulmonary tuberculosis in Lishui City, Zhejiang Province.

OBJECTIVE: The purpose of this study was to collect data on the current state of patient delay by patients with tuberculosis (TB) in Lishui City, Zhejiang Province who were under the care of a TB-designated hospital from 2011 to 2021 and to analyze the factors that contribute to this problem in order to provide a scientific basis for the prevention and control of TB. METHODS: In this observational study, we collected data on patients with pulmonary TB that were reported to the Chinese government's disease prevention and control information system by the Traditional Chinese Medicine Hospital in Lishui City between 2011 and 2021. The data included demographics like age, gender, occupation, household registration, current address, date of symptoms, date of first visit, and etiology results. Multivariate logistic regression analysis was used to analyze the factors influencing patient delay by patients with pulmonary TB. RESULTS: There were 3,190 cases of pulmonary TB treated in a TB-designated hospital in Lishui City, Zhejiang Province, between 2011 and 2021. Of these, 2,268 involved patient delay, with the delay rate of 71.10% and the median (Q25, Q75) days of patient delay being 36 (25, 72) days. Results of multivariate logistic regression analysis indicated the presence of risk factors-age > 60 years old (OR = 1.367, 95% CI: 1.144 ~ 1.632), pathogen positive (OR = 1.211, 95% CI: 1.033 ~ 1.419), and employed as peasants (OR = 1.353, 95% CI:1.144 ~ 1.601) for patient delay in patients with pulmonary TB. Patients with diabetes mellitus made up 64.94% of the pulmonary TB population, which was lower than the 71.58% of patients without diabetes mellitus (χ2 = 4.602, P = 0.032). Additionally, the presence of diabetes mellitus may be a protective factor in patient delay in patients with pulmonary TB (OR = 0.641, 95% CI: 0.481 ~ 0.856). CONCLUSION: High rates of patient delay, age > 60 years old, a positive etiology, and being employed as peasants are all possible risk factors for pulmonary TB in Lishui City, Zhejiang Province.

Assessment of Effective Anti-TB Regimens and Adverse Outcomes Related Risk Factors in the Elderly and Senile-Aged TB Patients.

Objective: Compared to younger patients with tuberculosis (TB), elderly and senile-aged patients with TB had a higher incidence of adverse outcomes particularly in terms of lost to follow-up and deaths. Our study aimed to gain insight into the effectiveness of anti-tuberculosis (anti-TB) treatment in the elderly or senile-aged patients and identify the risk factors for adverse outcomes. Methods: The case information was obtained from the "Tuberculosis Management Information System". From January 2011 to December 2021, this retrospective analysis was conducted in Lishui City, Zhejiang Province to observe and record the outcomes of elderly patients diagnosed with TB who agreed to receive anti-TB and(or) traditional Chinese medicine(TCM) treatment. We also employed a logistic regression model to analyze the risk factors for adverse outcomes. Results: Among the 1191 elderly or senile-aged patients with TB who received the treatment, the success rate was 84.80% (1010/1191). Using logistic regression analysis, several risk factors for adverse outcomes (failure, death, loss to follow-up) were identified, including age ≥ 80 years (OR 2.186, 95% CI 1.517~3.152, P<0.001), lesion area ≥ 3 lung fields (OR 0.410, 95% CI 0.260~0.648, P<0.001), radiographic lesions failing to improve after 2 months of treatment (OR 2.048, 95% CI 1.302~3.223, P=0.002), sputum bacteriology failing to turn negative after 2 months of treatment (OR 2.213, 95% CI 1.227~3.990, P=0.008), lack of a standardized treatment plan (OR 2.095, 95% CI 1.398~3.139, P<0.001), and non-involvement of traditional Chinese medicine (OR 2.589, 95% CI 1.589~4.216, P<0.001). Conclusion: The anti-TB treatment success rate in the elderly and senile-aged patients is suboptimal. Contributing factors include advanced age, extensive lesions, and low sputum negative conversion rate during the intensive treatment phase. The results will informative and could be useful for policy maker for to control of reemergence of TB in big cities.

Reducing Contact Resistance in Organic Field-Effect Transistors: A Comprehensive Comparison between 2D and Microrod Single Crystals.

A comprehensive comparison of organic single crystals based on a single material but with different dimensions provides a unique approach to probe their carrier injection mechanism. In this report, both two-dimensional (2D) and microrod single crystals with the same crystalline structure of an identical thiopyran derivative, 7,14-dioctylnaphtho[2,1-f:6,5-f']bis(cyclopentane[b]thiopyran) (C8-SS), are grown on a glycerol surface with the space-confined method. Organic field-effect transistors (OFETs) based on the 2D C8-SS single crystal exhibit superior performance compared with those based on the microrod single crystal, particularly in their contact resistance (RC). It is demonstrated that the resistance of the crystal bulk in the contact region plays a key role in RC of the OFETs. Thus, among the 30 devices tested, the microrod OFETs typically appear contact-limited, whereas the 2D OFETs possess significantly reduced RC arising from the tiny thickness of the 2D single crystal. The 2D OFETs show high operational stability and high channel mobility up to 5.7 cm2/V·s. The elucidation of the contact behavior highlights the merits and great potential of 2D molecular single crystals in organic electronics.

Allopolyploid origin and niche expansion of Rhodiola integrifolia (Crassulaceae).

Polyploidy after hybridization between species can lead to immediate post-zygotic isolation, causing saltatory origin of new species. Although the incidence of polyploidization in plants is high, it is thought that a new polyploid lineage can succeed only if it establishes a new ecological niche divergent from its progenitor lineages. We tested the hypothesis that Rhodiola integrifolia from North America is an allopolyploid produced by R. rhodantha and R. rosea and determined whether its survival can be explained by the niche divergence hypothesis. To this end, we sequenced two low-copy nuclear genes (ncpGS and rpb2) in a phylogenetic analysis of 42 Rhodiola species and tested for niche equivalency and similarity using Schoener's D as the index of niche overlap. Our phylogeny-based approach showed that R. integrifolia possesses alleles from both R. rhodantha and R. rosea. Dating analysis showed that the hybridization event that led to R. integrifolia occurred ca. 1.67 Mya and niche modeling analysis showed that at this time, both R. rosea and R. rhodantha may have been present in Beringia, providing the opportunity for the hybridization event. We also found that the niche of R. integrifolia differs from that of its progenitors in both niche breadth and optimum. Taken together, these results confirm the hybrid origin of R. integrifolia and support the niche divergence hypothesis for this tetraploid species. Our results underscore the fact that lineages with no current overlapping distribution could produce hybrid descendants in the past, when climate oscillations made their distributions overlap.

A New Dressing System for Wound in Enhanced-Recovery Total Hip Arthroplasty: A Randomized and Controlled Trial.

BACKGROUND: Currently, there is a paucity of recommendations in regards to dressing selection within the enhanced recovery after surgery protocol. We devised a new dressing system to accelerate the recovery after total hip arthroplasty (THA). We aimed to present our experience with this new dressing system as an adjunct to wound management in THA and to evaluate its performance. METHODS: From September 2020 to August 2021, we prospectively enrolled 124 patients who underwent a primary THA. The patients were randomly assigned to the intervention (the new dressing system group) or the control (the traditional gauze dressing) group. The primary outcome measures of this study were numbers of dressing changes, postoperative lengths of stay, wound scores including the Stony Brook Scar Evaluation Scale and ASEPSIS scores and wound-related complications. The secondary outcomes include satisfaction scores, dressing-related costs, and pain and functional recovery scores. RESULTS: The intervention group numbers of dressing changes and postoperative lengths of stay were significantly less than the control group (P < .001, P < .001). During the one-month follow-up, the Stony Brook Scar Evaluation Scale in the intervention group was significantly better than that in the control group (P < .001). The intervention group satisfaction was significantly higher than that in the control group (P < .001). There were no statistically significant differences between the two groups in terms of dressing-related costs and pain and function scores. CONCLUSION: The new dressing system could significantly reduce the number of dressing changes and postoperative lengths of stay and increase patient satisfaction scores, which can be an ideal adjunct to wound management in enhanced-recovery THA.

Clinicopathological and predictive value of MAIT cells in non-small cell lung cancer for immunotherapy.

BACKGROUND: Immune-checkpoint inhibitors (ICIs) remain ineffective in a large group of non-small cell lung cancer (NSCLC) patients. Mucosal-associated invariant T (MAIT) cells, a population of unconventional innate-like T lymphocytes abundant in the human body, play important roles in human malignancies. Little is known about the immune characteristics of MAIT cells in NSCLC and correlation with prognosis and response rate of ICIs treatment. METHODS: To investigate the distribution, activation status, and function of MAIT cells in NSCLC patients and their correlations with anti-PD-1 immunotherapy, MAIT cells in peripheral blood, tumor and paratumor samples from NSCLC patients with or without anti-PD-1 immunotherapy were analyzed using flow cytometry and single-cell RNA-sequencing. RESULTS: MAIT cells were enriched in the tumor lesions of NSCLC patients migrating from peripheral blood via the CCR6-CCL20 axis. Both peripheral and tumor-infiltrating MAIT cells displayed an exhausted phenotype with upregulated PD-1, TIM-3, and IL-17A while less IFN-γ. Anti-PD-1 therapy reversed the function of circulating MAIT cells with higher expression of IFN-γ and granzyme B. Subcluster MAIT-17s (defined as cells highly expressing exhausted and Th17-related genes) mainly infiltrated in the non-responsive tissues, while the subcluster MAIT-IFNGRs (cells expressing genes related to cytotoxic function) were mainly enriched in responsive tissues. Moreover, we found predictive value of circulating MAIT cells for anti-PD-1 immunotherapy in NSCLC patients. CONCLUSIONS: MAIT cells shifted to an exhausted tumor-promoting phenotype in NSCLC patients and the circulating MAIT subset could be a predictor for patients who respond to anti-PD-1 immunotherapy.

Bone marrow stromal cell-derived exosomal circular RNA improves diabetic foot ulcer wound healing by activating the nuclear factor erythroid 2-related factor 2 pathway and inhibiting ferroptosis.

BACKGROUND: Diabetic foot ulcer (DFU) remains a serious chronic diabetic complication that can lead to disability. CircRNA-itchy E3 ubiquitin protein ligase (circ-ITCH) was observed to be down-regulated in diabetic retinopathy and diabetic nephropathy, and overexpression of circ-ITCH could inhibit the processes of these diseases. However, the detailed physiological and pathological functions of circ-ITCH in wound healing of DFU remain undetermined. METHODS: Exosomes derived from bone marrow stromal cells (BMSCs) were isolated and identified. Cell viability and angiogenesis of human umbilical vein endothelial cells (HUVECs) were evaluated by cell counting kit-8 (CCK-8) and tube formation assays, respectively. The interplays of circ-ITCH, TATA-Box-binding protein associated factor 15 (TAF15) and nuclear factor erythroid 2-related factor 2 (Nrf2) mRNA were analysed by RNA immunoprecipitation (RIP), fluorescence in situ hybridization (FISH) combined immunofluorescent staining and RNA pull-down assays. qRT-PCR, western blot or immunohistochemistry (IHC) were used to measure the expression of circ-ITCH, TAF15, Nrf2, vascular endothelial growth factor (VEGFR) and ferroptosis-related makers. The mice DFU model was established to verify the in vitro results. RESULTS: Circ-ITCH was down-regulated in in vitro and in vivo models of DFU. Deferoxamine (DFO), an iron chelating agent, improved the viability and angiogenic ability of high glucose (HG)-treated HUVECs. Overexpression of circ-ITCH or co-cultured with exosomal circ-ITCH from BMSCs could alleviate HG-induced ferroptosis and improve the angiogenesis ability of HUVECs. Circ-ITCH in HUVECs recruited TAF15 protein to stabilize Nrf2 mRNA, thus activating the Nrf2 signalling pathway and suppressing ferroptosis. Exosomal circ-ITCH from BMSCs also accelerated the wound healing process by inhibiting ferroptosis in the DFU mice in a time-dependent manner. CONCLUSION: Exosomal circ-ITCH from BMSCs inhibited ferroptosis and improved the angiogenesis of HUVECs through activation of the Nrf2 signalling pathway by recruiting TAF15 protein, ultimately accelerating the wound healing process in DFU.

A modified biodegradable mesh ureteral stent for treating ureteral stricture disease.

Ureteral stricture disease (USD) is a common urologic condition. Patients with ureteral stricture disease may suffer from ipsilateral flank pain, nausea, urinary calculi, infection, and impaired renal function. The treatments of USD include surgery, followed by implantation of the ureteral stent to aid the drainage of the urine. The traditional ureteral stent may sometimes cause urological infection, encrustation, and discomfort. To decrease the complication of the ureteral stent, we modified the structure and material based on the traditional ureteral stent. The traditional nondegradable Double-J shape tubular ureteral stent was turned into the biodegradable mesh ureteral stent. The modified mesh ureteral stent and Double-J ureteral stent were inserted into the ureters of the USD animals, respectively. The results of the gross morphology, serology, urinalysis, histology, microstructure, et al. demonstrated that modified mesh ureteral stent has a favorable ability in supporting the ureter and has no effect on cell proliferation, migration, apoptosis, and cell cycle of the human uroepithelial cells. The mesh ureteral stent could relieve ureter obstruction and can be slowly biodegraded after 3-5 months of implantation without the need for a second surgery to remove the stent. Compared to the Double-J ureteral stent, the modified mesh ureteral stent has a lower rate of urinary tract infection and less encrustation. It is expected to be an alternative treatment approach for USD. However, due to the limited number of animals and clinical data, further study focused on the application value in clinical practice are essential. STATEMENT OF SIGNIFICANCE: This study demonstrates: 1. A modified biodegradable mesh ureteral stent; 2. Without the need for a second surgery to remove the stent; 3. A lower rate of urinary tract infection and less encrustation than a double-J ureteral stent; 4. An alternative treatment approach for USD.

The Controversy of Pepsinogen A/Pepsin A in Detecting Extra-Gastroesophageal Reflux.

BACKGROUND: Pepsinogen A (PGA)/pepsin A is often used as a diagnostic marker of extra-gastroesophageal reflux. We aimed to explore whether its positivity in upper aerodigestive tract (UADT) was specific enough to diagnose reflux. METHODS: PGA/pepsin A protein levels were examined in 10 types of tissues and 10 types of body fluid by immunological staining, western blot or Elisa, using three different commercially available brands simultaneously. Liquid chromatography-tandem mass spectrometry parallel reaction monitoring (LC-MS/MS PRM) served as a gold reference for the detection of PGA/pepsin A proteins. PGA gene expression was analyzed by reverse transcriptase sequencing methods for tissue samples. Specifically, 24 hour pH monitoring technique was conducted for patients who donated saliva samples. RESULTS: Eight out of ten types of human tissue samples (stomach, esophagus, lung, kidney, colon, parotid gland, nasal turbinate and nasal polyps) were confirmed positive for PGA/pepsin A gene and protein by genetic and PRM technique, respectively. Two out of ten types of body fluid samples (gastric fluid, urine) were confirmed positive for PGA/pepsin A protein by PRM technique. The consistence rates of PGA/pepsin A positivity among three commercial antibody brands and Elisa kit were poor, and Elisa results of salivary did not match with 24-hour pH monitoring. CONCLUSIONS: Multiple tissues and body fluid could be detected baseline expression levels of PGA/pepsin A gene and protein. However, those commercially available PGA/pepsin A antibodies achieved poor sensitivity and specificity, therefore, relying on the detection of PGA/pepsin A in UADT by single antibodies to diagnose extra-gastroesophageal reflux without a specific positive cut-off value is unreliable.

Comparison of Clinical and Radiological Outcomes between Calibratable Patient-Specific Instrumentation and Conventional Operation for Medial Open-Wedge High Tibial Osteotomy: A Randomized Controlled Trial.

Background: High tibial osteotomy (HTO) is an effective surgery in treating medial compartment knee osteoarthritis (KOA) combined with varus deformity. An accurate orthopaedy is the key and challenge to the success of HTO. Therefore, we designed a calibratable patient-specific instrumentation (PSI) to assist surgery and evaluated its accuracy and clinical outcomes by comparing with conventional operation (CO). Materials and Methods: 37 patients (39 knees) with medial compartment KOA were randomly divided into the PSI and CO groups and underwent medial open-wedge high tibial osteotomy (MOWHTO) from September 2020 to May 2021. The postoperative radiological outcomes were compared with the preoperative measurements or target values to evaluate the accuracy of correction in the two groups. The American Knee Society Score (AKSS), complication rate, number of intraoperative radiation exposures, blood loss volume, and operative duration were analysed to evaluate the clinical outcomes in the two groups. Results: The designed target values were better achieved in the PSI group than in the CO group. The mean absolute difference between the postoperative measurements and preoperative targets was significantly lower in the PSI group than in the CO group (weight-bearing line (WBL) ratio, 1.97 ± 1.83% vs.5.42 ± 4.41%, P = 0.002; hip-knee-ankle (HKA) angle, 1.12 ± 0.86° vs. 2.27 ± 1.97°, P = 0.018). The operative duration was significantly shorter (P = 0.014), and the number of radiation exposures (P < 0.001) and volume of intraoperative blood loss (P = 0.003) were significantly lower in the PSI group than in the CO group. The clinical AKSS score at 3 and 6 months postoperatively and the functional AKSS score at 3 months postoperatively were significantly higher in the PSI group than in the CO group (P = 0.042, 0.040, and 0.034, respectively). Conclusion: For patients with medial compartment KOA, calibratable PSI can assist the surgeon in MOWHTO with superior accuracy and clinical efficacy. This study was conducted under Randomized Controlled Trial Details (RCT) with Registry Number ChiCTR2000038619.

Cold Nanozyme for Precise Enzymatic Antitumor Immunity.

Precise catalysis is pursued for the biomedical applications of artificial enzymes. It is feasible to precisely control the catalysis of artificial enzymes via tunning the temperature-dependent enzymatic kinetics. The safety window of cold temperatures (4-37 °C) for the human body is much wider than that of thermal temperatures (37-42 °C). Although the development of cold-activated artificial enzymes is promising, there is currently a lack of suitable candidates. Herein, a cold-activated artificial enzyme is presented with Bi2Fe4O9 nanosheets (NSs) as a paradigm. The as-obtained Bi2Fe4O9 NSs possess glutathione oxidase (GSHOx)-like activity under cold temperature due to their pyroelectricity. Bi2Fe4O9 NSs trigger the cold-enzymatic death of tumor cells via apoptosis and ferroptosis, and minimize the off-target toxicity to normal tissues. Moreover, an interventional device is fabricated to intelligently and remotely control the enzymatic activity of Bi2Fe4O9 NSs on a smartphone. With Bi2Fe4O9 NSs as an in situ vaccine, systemic antitumor immunity is successfully activated to suppress tumor metastasis and relapse. Moreover, blood biochemistry analysis and histological examination indicate the high biosafety of Bi2Fe4O9 NSs for in vivo applications. This cold nanozyme provides a strategy for cancer vaccines, which can benefit the precise control over catalytic nanomedicines.

The divergent effects of astrocyte ceruloplasmin on learning and memory function in young and old mice.

Ceruloplasmin (CP) plays an important role in maintaining iron homeostasis. Cp gene knockout (Cp-/-) mice develop a neurodegenerative disease with aging and show iron accumulation in the brain. However, iron deficiency has also been observed in 3 M Cp-/- mice. The use of systemic Cp gene knockout is insufficient to reveal specific functions for CP in the central nervous system. Considering recent discoveries that astrocytes synthetize the majority of brain CP, we generated astrocyte conditional Cp knockout (CpGfapcKO) mice, and found that iron contents decreased in the cerebral cortex and hippocampus of young (6 M) and old (18 M) CpGfapcKO mice. Further experiments revealed that 6 M CpGfapcKO mice exhibited impaired learning and memory function, while 18 M CpGfapcKO mice exhibited improved learning and memory function. Our study demonstrates that astrocytic Cp deletion blocks brain iron influx through the blood-brain-barrier, with concomitantly increased iron levels in brain microvascular endothelial cells, resulting in brain iron deficiency and down-regulation of ferritin levels in neurons, astrocytes, microglia and oligodendrocytes. At the young age, the synapse density, synapse-related protein levels, 5-hydroxytryptamine and norepinephrine, hippocampal neurogenesis and myelin formation were all decreased in CpGfapcKO mice. These changes affected learning and memory impairment in young CpGfapcKO mice. In old CpGfapcKO mice, iron accumulation with aging was attenuated, and was accompanied by the alleviation of the ROS-MAPK-apoptosis pathway, Tau phosphorylation and ß-amyloid aggregation, thus delaying age-related memory decline. Overall, our results demonstrate that astrocytic Cp deletion has divergent effects on learning and memory function via different regulatory mechanisms induced by decreased iron contents in the brain of mice, which may present strategies for the prevention and treatment of dementia.