Age- and sex-specific 99th percentile upper reference limits for high-sensitivity cardiac troponin T in Chinese older people: Real-world data mining.

BACKGROUND: This study aims to investigate the impact of age and sex on high-sensitivity cardiac troponin T (hs-cTnT) and establish 99th percentile upper reference limits (URLs) in older individuals utilizing large-scale real-world data. METHODS: 40,530 outpatient hs-cTnT results were obtained from the laboratory database from January 1, 2018, to December 31, 2023. Our study included 4,199 elderly outpatients (aged ≥ 60) without cardiovascular disease or other heart-related chronic conditions. Nested analysis of variance was used to explore the necessity of partitioning reference intervals (RIs) by sex and age groups. RIs were established by the refineR algorithm and assessed based on ≤ 10% test results of validation data set outside the new RIs. RESULTS: RIs for hs-cTnT in the older population needed to be partitioned by sex and age groups ([standard deviation ratio] SDRage = 0.75; SDRsex = 0.49). URLs in older Chinese adults were 21.8 ng/L for males, 16.5 ng/L for females, and 20.7 ng/L for the overall participant group. URLs for males aged 60-69, 70-79, and ≥ 80 were 13.7, 19.4, and 31.0 ng/L, respectively. Female values were 10.1, 17.2, and 22.0 ng/L. Importantly, manufacturer-reported RIs do not suffice for Chinese individuals aged ≥ 70. Validation data showed that 2.7-5.2% of test results fell outside the new RIs, confirming the validity of the results. CONCLUSION: This study establishes age- and sex-specific 99th percentile URLs for hs-cTnT in Chinese older individuals, thereby enhancing the accuracy of clinical assessments.

Light and matter co-confined multi-photon lithography.

Mask-free multi-photon lithography enables the fabrication of arbitrary nanostructures low cost and more accessible than conventional lithography. A major challenge for multi-photon lithography is to achieve ultra-high precision and desirable lateral resolution due to the inevitable optical diffraction barrier and proximity effect. Here, we show a strategy, light and matter co-confined multi-photon lithography, to overcome the issues via combining photo-inhibition and chemical quenchers. We deeply explore the quenching mechanism and photoinhibition mechanism for light and matter co-confined multiphoton lithography. Besides, mathematical modeling helps us better understand that the synergy of quencher and photo-inhibition can gain a narrowest distribution of free radicals. By using light and matter co-confined multiphoton lithography, we gain a 30 nm critical dimension and 100 nm lateral resolution, which further decrease the gap with conventional lithography.

Outcomes of Breast-Conserving Therapy in Patients With Inflammatory Breast Cancer: A Meta-Analysis.

INTRODUCTION: Inflammatory breast cancer (IBC) is a rare and aggressive form of breast cancer. Currently, patients who respond to neoadjuvant chemotherapy (NAC) are treated with mastectomy and axillary lymph node dissection. This study aimed to synthesize real-world data to evaluate the feasibility of breast-conserving therapy (BCT), sentinel lymph node (SLN), and sentinel lymph node biopsy (SLNB) for patients with IBC who respond to NAC. METHODS: PubMed, Embase, and Cochrane Library databases were searched for relevant articles. Clinical studies that compared mastectomy with BCT for IBC treatment were reviewed. The primary outcomes were local recurrence rate and 5-y survival rate in patients with IBC who responded to NAC. Furthermore, the SLN detection rate and false-negative rate (FNR) for SLNB were also evaluated. RESULTS: In the final analysis, 17 studies were included. The pooled estimates of the local recurrence rate for mastectomy and no surgical intervention were 18.6% and 15.9%, respectively (P = 0.956). Five-y survival was similar for mastectomy, partial mastectomy, and no surgical intervention (45.8%, 57.1%, and 39.4%, respectively). The pooled estimates of the SLN detection rate and FNR for SLNB were 81.9% and 21.8%, respectively. CONCLUSIONS: Among patients with IBC who respond to NAC, the local recurrence and 5-y survival rates in those undergoing BCT are noninferior to the rates in those undergoing mastectomy; therefore, BCT could be a feasible option for surgical management. However, a poor SLN detection rate and a high FNR were found in patients undergoing SLNB. Further large-scale clinical studies are required to confirm our findings.

Validation of a Metagenomic Next-Generation Sequencing Assay for Lower Respiratory Pathogen Detection.

Lower respiratory infection (LRI) is the most fatal communicable disease, with only a few pathogens identified. Metagenomic next-generation sequencing (mNGS), as an unbiased, hypothesis-free, and culture-independent method, theoretically enables the detection of all pathogens in a single test. In this study, we developed and validated a DNA-based mNGS method for the diagnosis of LRIs from bronchoalveolar lavage fluid (BALF). We prepared simulated in silico data sets and published raw data sets from patients to evaluate the performance of our in-house bioinformatics pipeline and compared it with the popular metagenomics pipeline Kraken2-Bracken. In addition, a series of biological microbial communities were used to comprehensively validate the performance of our mNGS assay. Sixty-nine clinical BALF samples were used for clinical validation to determine the accuracy. The in-house bioinformatics pipeline validation showed a recall of 88.03%, precision of 99.14%, and F1 score of 92.26% via single-genome simulated data. Mock in silico microbial community and clinical metagenomic data showed that the in-house pipeline has a stricter cutoff value than Kraken2-Bracken, which could prevent false-positive detection by the bioinformatics pipeline. The validation for the whole mNGS pipeline revealed that overwhelming human DNA, long-term storage at 4°C, and repeated freezing-thawing reduced the analytical sensitivity of the assay. The mNGS assay showed a sensitivity of 95.18% and specificity of 91.30% for pathogen detection from BALF samples. This study comprehensively demonstrated the analytical performance of this laboratory-developed mNGS assay for pathogen detection from BALF, which contributed to the standardization of this technology. IMPORTANCE To our knowledge, this study is the first to comprehensively validate the mNGS assay for the diagnosis of LRIs from BALF. This study exhibited a ready-made example for clinical laboratories to prepare reference materials and develop comprehensive validation schemes for their in-house mNGS assays, which would accelerate the standardization of mNGS testing.

Multilaboratory assessment of metagenomic next-generation sequencing for unbiased microbe detection.

Introduction: Metagenomic next-generation sequencing (mNGS) assay for detecting infectious agents is now in the stage of being translated into clinical practice. With no approved approaches or guidelines available, laboratories adopt customized mNGS assays to detect clinical samples. However, the accuracy, reliability, and problems of these routinely implemented assays are not clear. Objectives: To evaluate the performance of 90 mNGS laboratories under routine testing conditions through analyzing identical samples. Methods: Eleven microbial communities were generated using 15 quantitative microbial suspensions. They were used as reference materials to evaluate the false negatives and false positives of participating mNGS protocols, as well as the ability to distinguish genetically similar organisms and to identify true pathogens from other microbes based on fictitious case reports. Results: High interlaboratory variability was found in the identification and the quantitative reads per million reads (RPM) values of each microbe in the samples, especially when testing microbes present at low concentrations (1 × 103 cell/ml or less). 42.2% (38/90) of the laboratories reported unexpected microbes (i.e. false positive problem). Only 56.7% (51/90) to 83.3% (75/90) of the laboratories showed a sufficient ability to obtain clear etiological diagnoses for three simulated cases combined with patient information. The analysis of the performance of mNGS in distinguishing genetically similar organisms in three samples revealed that only 56.6% to 63.0% of the laboratories recovered RPM ratios (RPM S. aureus /RPM S. epidermidis ) within the range of a 2-fold change of the initial input ratios (indicating a relatively low level of bias). Conclusion: The high interlaboratory variability found in both identifying microbes and distinguishing true pathogens emphasizes the urgent need for improving the accuracy and comparability of the results generated across different mNGS laboratories, especially in the detection of low-microbial-biomass samples.

Routine intraoperative cholangiography during laparoscopic cholecystectomy: application of the 2016 WSES guidelines for predicting choledocholithiasis.

BACKGROUND: Routine use of intraoperative cholangiography (IOC) during laparoscopic cholecystectomy (LC) for detecting common bile duct stones remains controversial. The 2016 World Society of Emergency Surgery (WSES) guidelines on acute calculous cholecystitis proposed a risk stratification for choledocholithiasis. Our present study aimed to (1) examine the findings of common bile duct (CBD) stones in patients underwent LC with routine use of IOC, and (2) validate the 2016 WSES risk classes for predicting choledocholithiasis. METHODS: All patients had LC with IOC routinely performed from November 2012 to December 2017 were reviewed retrospectively. Patients were classified into high-, intermediate-, and low-risk groups based on the 2016 WSES risk classes with modification. RESULTS: A total of 990 patients with LC and routine IOC were enrolled. CBD stones were detected in 197 (19.9%) patients. The rate of CBD stone detected in low-, intermediate-, high-risk groups were 0%, 14.2%, and 89.6%, respectively. Predictors as following: evidence of CBD stones on abdominal ultrasound or computed tomography, CBD diameter > 6 mm, total bilirubin > 4 mg/dL, bilirubin level = 1.8-4 mg/dL, abnormal liver biochemical test result other than bilirubin, presence of clinical gallstone pancreatitis had statistical significance between patients with and without CBD stones. Major bile duct injury was found in 4 patients (0.4%). All 4 patients had uneventful recovery after repair surgery. CONCLUSIONS: Based on our study results, the 2016 WSES risk classes for choledocholithiasis could be an effective approach for predicting the risk of choledocholithiasis. Considering its advantages for detecting CBD stones and biliary injuries, the routine use of IOC is still suggested.

A Self-Healing and Shape Memory Polymer that Functions at Body Temperature.

Dual-functional polymeric system combining shape memory with self-healing properties has attracted increasingly interests of researchers, as both of these properties are intelligent and promising characteristics. Moreover, shape memory polymer that functions at human body temperature (37 °C) are desirable because of their potential applications in biomedical field. Herein, we designed a polymer network with a permanent covalent crosslinking and abundant weak hydrogen bonds. The former introduces elasticity responsible and maintain the permanent shape, and the latter contributes to the temporary shape via network rearrangement. The obtained PDMS-COO-E polymer films exhibit excellent mechanical properties and the capability to efficiently self-heal for 6 h at room temperature. Furthermore, the samples turn from a viscous state into an elastic state at 37 °C. Therefore, this polymer has shape memory effects triggered by body temperature. This unique material will have a wide range of applications in many fields, containing wearable electronics, biomedical devices, and 4D printing.

Effects of Sr on the microstructure, mechanical properties and corrosion behavior of Mg-2Zn-xSr alloys.

The effects of the addition of Sr on the microstructures, mechanical properties and bio-corrosion properties of Mg-2Zn alloys were investigated. Examination of the microstructures indicates that Sr addition promoted grain refinement and the formation of secondary phases. The results for the mechanical and corrosion property analyses show that the Mg-2Zn-0.2Sr alloy exhibited the best mechanical properties and bio-corrosion resistance. Notably, fine grain structure can promote strength and ductility, while the excessive secondary phases Mg17Sr2 resulted in the degradation of mechanical performance. Moreover, corrosion resistance could be improved by reducing the impurity concentrations and forming a denser corrosion product layer, while the secondary phases accelerated the corrosion process by forming micro-galvanic couples with the Mg matrix. It is considered that the addition of Sr (0.2%) represents the main contributing factor to these improved properties. The Mg-2Zn-0.2Sr alloy provides excellent strength and corrosion resistance for biomedical applications.

Effect of Homogenization on Microstructure Characteristics, Corrosion and Biocompatibility of Mg-Zn-Mn-xCa Alloys.

The corrosion behaviors of Mg-2Zn-0.2Mn-xCa (denoted as MZM-xCa alloys) in homogenization state have been investigated by immersion test and electrochemical techniques in a simulated physiological condition. The microstructure features were characterized using scanning electron microscopy (SEM), X-ray diffraction (XRD), transmission electron microscopy (TEM) and electron probe microanalysis (EPMA), and the corrosion mechanism was illustrated using atomic force microscope (AFM), X-ray photoelectron spectroscopy (XPS) and confocal laser scanning microscopy (CLSM). The electrochemical and immersion test verify the MZM-0.38% Ca owns the best corrosion performance with the corrosion rate of 6.27 mm/year. Furthermore, the film layer of MZM-0.38% Ca is more compact and denser than that of others. This improvement could be associated with the combined effects of the suitable content of Zn/Ca dissolving into the α-Mg matrix and the modification of Ca-containing compounds by heat-treatment. However, the morphologies were transformed from uniform corrosion to localized pitting corrosion with Ca further addition. It could be explained that the excessive Ca addition can strengthen the nucleation driving force for the second phase formation, and the large volumes fraction of micro-galvanic present interface sites accelerate the nucleation driving force for corrosion propagation. In addition, in vitro biocompatibility tests also show the MZM-0.38% Ca was safe to bone mesenchymal stem cells (BMSCs) and was promising to be utilized as implant materials.

Distinct Mechanical and Self-Healing Properties in Two Polydimethylsiloxane Coordination Polymers with Fine-Tuned Bond Strength.

Coordination bonds are effective for constructing highly efficient self-healing materials as their strength is highly tunable. To design self-healing polymers with better performance, it is important to get a profound understanding of the structure-property relationships. However, this is challenging for self-healing polymers based on coordination bonds, because many parameters, such as bond energy, bond dynamics, and coordination number will have an essential effect on the mechanical and self-healing properties of the polymer. In this work, we synthesized two poly(dimethylsiloxane) (PDMS) polymers cross-linked by different Zn(II)-diiminopyridine coordination complexes (denoted as PDMS-NNN-Zn, PDMS-MeNNN-Zn respectively). The two cross-linking Zn(II)-diiminopyridine complexes are similar in coordination modes, but differ in coordination dynamics. As manifested by ITC, rheology, and tensile experiments, we confirm that the coordination bond in PDMS-MeNNN-Zn polymer films is weaker but more dynamic. Consequently, the PDMS-MeNNN-Zn polymer has poorer mechanical strength but higher stretchability and better self-healing properties. The inflicted cracks on PDMS-MeNNN-Zn polymer films can be completely healed after healing at room temperature for only 30 min with healing efficiencies higher than 90%. Such fast self-healing properties have never been achieved in self-healing polymers based on coordination bonds. Our results also demonstrate the important impact of the thermodynamic stability and kinetic lability of coordination complexes on the mechanical and self-healing properties of polymers. Such a comprehensive understanding is helpful for further design of novel synthetic polymers, which can achieve an optimal balance between the mechanical strength and self-healing performance.

Clinical and histopathological characteristics in patients with scarring folliculitis type of acne inversa.

Objective: This study was designed to study the clinical and histopathological characteristics of patients with the scarring folliculitis type acne inversa in Chinese population. Methods: A total of 21 patients with acne inversa and 6 controls without known dermatological disease were recruited from outpatient department of dermatology and orthopedic surgery. Two-millimeter punch biopsies were taken from 8 patients with acne inversa and 6 controls, fixed in formalin, embedded in paraffin and stained with haematoxylin and eosin prior to histopathological analysis. Results: There were 12 patients (57.14%) belonging to the scarring folliculitis type presented with double comedones, papules, nodules, depressed scars, and were mainly Hurley stage I (66.67%). Many of the scarring folliculitis type were smokers (58.33%), some had a history of occupational exposure (41.67%) and some were overweight (50%), the mean BMI of which is 25.18±3.16 kg/m2. Histopathological changes such as perifollicular inflammation can be observed in scarring folliculitis type of acne inversa and controls as well. However, epidermal hyperplasia, follicular hyperplasia, sebaceous gland disappearance, destruction of hair follicle and sebaceous gland, collagen hyperplasia, perivascular inflammation, granulomatous inflammation, Micro thrombus were only seen in scarring folliculitis type. The mean surface area in patients (8073.36±15798.43 µm2) was smaller than that in controls (302059.08±502813.78 µm2), with statistically significant difference. (P = 0.024). Conclusion: The scarring folliculitis type in acne inversa in Chinese population could be characterized by depressed scars, double-ended comedones, epidermal cysts and had high proportion of smokers, or occupational exposure with lower Hurley stage, as well as diminished sebaceous gland. Further studies are needed to clarify the relations between the clinical subtypes of acne inversa and their corresponding genetypes.

[Mechanism of hetero-erythromycin resistant Staphylococcus aureus and a comparison of detection methods].

OBJECTIVE: To explore the phenotypes and genotypes of Staphylococcus aureus (S. aureus) hetero-resistant to erythromycin and clindamycin and compare their detection methods so as to report results accurately to guide clinical rational use of antibiotics. METHODS: D test was used to detect the phenotypes of S. aureus hetero-resistant to erythromycin. And then the results of two methods (automated instrument and disk diffusion) were analyzed. All strains were continuously passaged for 50 generations to verify the phenotypic and genotypic stability of hetero-resistance. ErmA, ermC and msrA genes were amplified by multiplex polymerase chain reaction (PCR). RESULTS: Among 95 erythromycin-sensitive strains, there were 70 strains hetero-resistant to erythromycin (73.7%). The primary 70 strains were all susceptive to erythromycin (MIC ≤ 0.25 µg/ml) and clindamycin (MIC ≤ 0.25 µg/ml) with the cards of GP-67 of VITEK2 Compact. With D tests, the results were difficult to observe. The passaged 70 strains were all resistant to erythromycin (MIC >8 µg/ml) and susceptible to clindamycin (MIC ≤ 0.25 µg/ml) and D test positive with the cards of GP-67 of VITEK2 Compact. The primary and 50(th) generation of herero-erythromycin resistant strains were stable in susceptibility test results. The primary and the 50(th)th generation strains were all ermA gene positive, ermC and msrA negative with PCR results. CONCLUSIONS: The phenotypes and genotypes of hetreo-erythromycin resistant S. aureus strains were stable. Missed detection with VITEK2 Compact may affect the proper use of erythromycin and clindamycin. Laboratory technicians should identify the erythromycin-susceptible strains by disk diffusion method.

Clinical application of real time-polymerase chain reaction in determining cytomegalovirus viral DNA load in renal transplant recipients.

BACKGROUND: Cytomegalovirus (CMV) remains a significant clinical problem among immunosuppressed renal transplant patients. Quantitative PCR assays have become the most common methods in the determination of CMV infections in transplant patients. This study was to determine the relationship between CMV infection and the acute rejection of the transplanted kidney. METHODS: Plasma samples from 77 renal transplant patients that were pre-transplant negative for CMV infection were tested using real-time quantitative PCR and CMV gene-specific primers. The detected viral loads were retrospectively compared with the acute rejection rate and the chronic or mild rejection rates of the renal transplant. RESULTS: CMV-DNA was detected in 29 of 77 recipients, yielding a positive rate of detection of 37.7% for this procedure. Twelve of the 21 recipients (57.1%) who suffered acute rejection had positive CMV-DNA. Among the 56 recipients suffered from chronic or mild rejection, 17 (30.4%) had positive CMV-DNA plasma. Moreover, of the 29 recipients who had detectable CMV-DNA after transplant, 12 (41.4%) suffered from acute rejection; of the 48 recipients with undetectable CMV-DNA, only nine (18.8%) developed acute rejection. Post-transplant patients with acute rejection had a higher rate (57.1% vs. 30.4%, P = 0.03) of post-transplant CMV infection than those with chronic or mild rejection. CONCLUSION: CMV infection is a risk factor of acute renal transplant rejection and CMV infection should be prevented and treated in renal transplant recipients.

Lasting controversy on ranibizumab and bevacizumab.

Vascular endothelial growth factor (VEGF), an important angiogenic factor that is able to stimulate the proliferation and migration of endothelial cells, is the best-studied hallmark of angiogenesis. Neovascularization is a major cause of age-related macular degeneration (AMD) which is a leading cause of blindness in the elderly population. Specific molecular inhibitors of VEGF have been proved to be useful in the treatment of AMD. Ranibizumab and Bevacizumab are structurally similar to anti-VEGF drugs in the treatment of AMD. Many studies have indicated that Ranibizumab and Bevacizumab are of roughly equal short-term efficacy and safety, Bevacizumab is an attractive alternative to Ranibizumab due to its lower cost. However, only Ranibizumab has received Food and Drug Administration (FDA) approval for the treatment of macular degeneration. More multicenter clinical trials are required to compare the relative efficacy and safety of these two drugs and some progress has been achieved. This review discusses the clinical effectiveness, safety, cost and other practical implications of Ranibizumab and Bevacizumab.