ObjectiveBased on ultra-performance liquid chromatography-quadrupole-electrostatic field orbitrap high resolution mass spectrometry（UPLC-Q-Orbitrap-MS）， the chemical constituents of Qili Qiangxin capsules was identified， and their distribution in vivo was analyzed. MethodsUPLC-Q-Orbitrap-MS was used to detect the sample solution of Qili Qiangxin capsules， as well as the serum， brain， heart， lung， spleen， liver and kidney tissues of mice after oral administration. Using the Thermo Xcalibur 2.2 software， the compound information database was constructed， and the molecular formulas of compounds corresponding to the quasi-molecular ions were fitted. Based on the information of retention time， accurate relative molecular mass and fragments， the compounds and their distribution in vivo were analyzed by comparing with the data of reference substances and literature. ResultsA total of 233 compounds， including 70 terpenoids， 60 flavonoids， 23 organic acids， 17 alkaloids， 20 steroids， 7 coumarins and 36 others， were identified or predicted from Qili Qiangxin capsules， 73 of which were identified matching with standard substances. Tissue distribution results showed that 71， 17， 38， 33， 32， 58 and 43 migrating components were detected in blood， brain， heart， lung， spleen， liver and kidney， respectively. Thirty-seven components were absorbed into the blood and heart， including quinic acid， benzoylaconitine benzoylmesaconine and so on. Fourteen components were absorbed into the blood and six tissues， including calycosin， methylnissolin， formononetin， alisol B， alisol A and so on. ConclusionThis study comprehensively analyzes the chemical components of Qili Qiangxin capsules and their distribution in vivo. Among them， astragaloside Ⅳ， salvianolic acid B， ginsenoside Rb₁， ginsenoside Rb₃， ginsenoside Rd， ginsenoside Rg₃， calycosin-7-glucoside， and sinapine may be the important components for the treatment of heart failure， which can provide useful reference for its quality control and research on pharmacodynamic material basis.

The number of patients with reduced blood volume due to haemorrhage, fractures, severe infections, extensive burns and tumours is increasing, and traditional blood products are no longer able to meet the increasing clinical demand. Therefore, plasma substitutes have become particularly important in fluid resuscitation, especially artificial colloidal solutions, which have a sustained volume expansion time and a good volume expansion effect, and can significantly improve the circulatory status of patients. This article aims to review the classification of artificial colloidal plasma substitutes and their research progress in clinical practice, in order provide a more rigorous, professional and standardized reference for medicine.

Purpose: The study aimed to comprehensively analyze testosterone and precursor concentrations in the testicular interstitial fluid (TIF) of men with azoospermia, exploring their significance in the testicular microenvironment and their correlation with testicular sperm retrieval outcomes. Materials and Methods: We analyzed 37 TIF samples, including 5 from men with obstructive azoospermia (OA) and 32 from men with non-obstructive azoospermia (NOA). Liquid chromatography with tandem mass spectrometry quantified testosterone and precursor levels. Comparative assessments of the outcomes of testicular sperm retrieval were performed between the OA and NOA groups as well as among men with NOA. Results: Men with NOA who had not undergone hormone treatment exhibited significantly higher intratesticular concentrations of testosterone (median 1,528.1 vs. 207.5 ng/mL), androstenedione (median 10.6 vs. 1.9 ng/mL), and 17-OH progesterone (median 13.0 vs. 1.8 ng/mL) than men diagnosed with OA. Notably, in the subgroup of patients with NOA subjected to medical treatment, men with successful sperm retrieval had significantly reduced levels of androstenedione (median androstenedione 5.7 vs. 18.5 ng/mL, p=0.004). Upon a more detailed analysis of these men who underwent hormone manipulation treatment, the testosterone/androstenedione ratio (indicative of HSD17B3 enzyme activity) was markedly increased in men with successful sperm retrieval (median: 365.8 vs. 165.0, p=0.008) compared with individuals with NOA who had unsuccessful sperm recovery. Furthermore, within the subset of men with NOA who did not undergo medical treatment before microdissection testicular sperm extraction but achieved successful sperm retrieval, the ratio of 17-OH progesterone/progesterone (indicative of CYP17A1 activity) was substantially higher. Conclusions The study suggests distinct testosterone biosynthesis pathways in men with compromised spermatogenesis and those with normal spermatogenesis. Among NOA men with successful retrieval after hormone optimization therapy, there was decreased androstenedione and increased HSD17B3 enzyme activity. These findings have diagnostic and therapeutic implications for the future.

Membrane proteins are integral components of cellular membranes, accounting for approximately 30% of the mammalian proteome and serving as targets for 60% of FDA-approved drugs. They are critical to both physiological functions and disease mechanisms. Their functional protein-protein interactions form the basis for many physiological processes, such as signal transduction, material transport, and cell communication. Membrane protein interactions are characterized by membrane environment dependence, spatial asymmetry, weak interaction strength, high dynamics, and a variety of interaction sites. Therefore, in situ analysis is essential for revealing the structural basis and kinetics of these proteins. This paper introduces currently available in situ analytical techniques for studying membrane protein interactions and evaluates the characteristics of each. These techniques are divided into two categories: label-based techniques (e.g., co-immunoprecipitation, proximity ligation assay, bimolecular fluorescence complementation, resonance energy transfer, and proximity labeling) and label-free techniques (e.g., cryo-electron tomography, in situ cross-linking mass spectrometry, Raman spectroscopy, electron paramagnetic resonance, nuclear magnetic resonance, and structure prediction tools). Each technique is critically assessed in terms of its historical development, strengths, and limitations. Based on the authors’ relevant research, the paper further discusses the key issues and trends in the application of these techniques, providing valuable references for the field of membrane protein research. Label-based techniques rely on molecular tags or antibodies to detect proximity or interactions, offering high specificity and adaptability for dynamic studies. For instance, proximity ligation assay combines the specificity of antibodies with the sensitivity of PCR amplification, while proximity labeling enables spatial mapping of interactomes. Conversely, label-free techniques, such as cryo-electron tomography, provide near-native structural insights, and Raman spectroscopy directly probes molecular interactions without perturbing the membrane environment. Despite advancements, these methods face several universal challenges: (1) indirect detection, relying on proximity or tagged proxies rather than direct interaction measurement; (2) limited capacity for continuous dynamic monitoring in live cells; and (3) potential artificial influences introduced by labeling or sample preparation, which may alter native conformations. Emerging trends emphasize the multimodal integration of complementary techniques to overcome individual limitations. For example, combining in situ cross-linking mass spectrometry with proximity labeling enhances both spatial resolution and interaction coverage, enabling high-throughput subcellular interactome mapping. Similarly, coupling fluorescence resonance energy transfer with nuclear magnetic resonance and artificial intelligence (AI) simulations integrates dynamic structural data, atomic-level details, and predictive modeling for holistic insights. Advances in AI, exemplified by AlphaFold’s ability to predict interaction interfaces, further augment experimental data, accelerating structure-function analyses. Future developments in cryo-electron microscopy, super-resolution imaging, and machine learning are poised to refine spatiotemporal resolution and scalability. In conclusion, in situ analysis of membrane protein interactions remains indispensable for deciphering their roles in health and disease. While current technologies have significantly advanced our understanding, persistent gaps highlight the need for innovative, integrative approaches. By synergizing experimental and computational tools, researchers can achieve multiscale, real-time, and perturbation-free analyses, ultimately unraveling the dynamic complexity of membrane protein networks and driving therapeutic discovery.

Purpose: The study aimed to comprehensively analyze testosterone and precursor concentrations in the testicular interstitial fluid (TIF) of men with azoospermia, exploring their significance in the testicular microenvironment and their correlation with testicular sperm retrieval outcomes. Materials and Methods: We analyzed 37 TIF samples, including 5 from men with obstructive azoospermia (OA) and 32 from men with non-obstructive azoospermia (NOA). Liquid chromatography with tandem mass spectrometry quantified testosterone and precursor levels. Comparative assessments of the outcomes of testicular sperm retrieval were performed between the OA and NOA groups as well as among men with NOA. Results: Men with NOA who had not undergone hormone treatment exhibited significantly higher intratesticular concentrations of testosterone (median 1,528.1 vs. 207.5 ng/mL), androstenedione (median 10.6 vs. 1.9 ng/mL), and 17-OH progesterone (median 13.0 vs. 1.8 ng/mL) than men diagnosed with OA. Notably, in the subgroup of patients with NOA subjected to medical treatment, men with successful sperm retrieval had significantly reduced levels of androstenedione (median androstenedione 5.7 vs. 18.5 ng/mL, p=0.004). Upon a more detailed analysis of these men who underwent hormone manipulation treatment, the testosterone/androstenedione ratio (indicative of HSD17B3 enzyme activity) was markedly increased in men with successful sperm retrieval (median: 365.8 vs. 165.0, p=0.008) compared with individuals with NOA who had unsuccessful sperm recovery. Furthermore, within the subset of men with NOA who did not undergo medical treatment before microdissection testicular sperm extraction but achieved successful sperm retrieval, the ratio of 17-OH progesterone/progesterone (indicative of CYP17A1 activity) was substantially higher. Conclusions The study suggests distinct testosterone biosynthesis pathways in men with compromised spermatogenesis and those with normal spermatogenesis. Among NOA men with successful retrieval after hormone optimization therapy, there was decreased androstenedione and increased HSD17B3 enzyme activity. These findings have diagnostic and therapeutic implications for the future.

Purpose: The study aimed to comprehensively analyze testosterone and precursor concentrations in the testicular interstitial fluid (TIF) of men with azoospermia, exploring their significance in the testicular microenvironment and their correlation with testicular sperm retrieval outcomes. Materials and Methods: We analyzed 37 TIF samples, including 5 from men with obstructive azoospermia (OA) and 32 from men with non-obstructive azoospermia (NOA). Liquid chromatography with tandem mass spectrometry quantified testosterone and precursor levels. Comparative assessments of the outcomes of testicular sperm retrieval were performed between the OA and NOA groups as well as among men with NOA. Results: Men with NOA who had not undergone hormone treatment exhibited significantly higher intratesticular concentrations of testosterone (median 1,528.1 vs. 207.5 ng/mL), androstenedione (median 10.6 vs. 1.9 ng/mL), and 17-OH progesterone (median 13.0 vs. 1.8 ng/mL) than men diagnosed with OA. Notably, in the subgroup of patients with NOA subjected to medical treatment, men with successful sperm retrieval had significantly reduced levels of androstenedione (median androstenedione 5.7 vs. 18.5 ng/mL, p=0.004). Upon a more detailed analysis of these men who underwent hormone manipulation treatment, the testosterone/androstenedione ratio (indicative of HSD17B3 enzyme activity) was markedly increased in men with successful sperm retrieval (median: 365.8 vs. 165.0, p=0.008) compared with individuals with NOA who had unsuccessful sperm recovery. Furthermore, within the subset of men with NOA who did not undergo medical treatment before microdissection testicular sperm extraction but achieved successful sperm retrieval, the ratio of 17-OH progesterone/progesterone (indicative of CYP17A1 activity) was substantially higher. Conclusions The study suggests distinct testosterone biosynthesis pathways in men with compromised spermatogenesis and those with normal spermatogenesis. Among NOA men with successful retrieval after hormone optimization therapy, there was decreased androstenedione and increased HSD17B3 enzyme activity. These findings have diagnostic and therapeutic implications for the future.

Purpose: The study aimed to comprehensively analyze testosterone and precursor concentrations in the testicular interstitial fluid (TIF) of men with azoospermia, exploring their significance in the testicular microenvironment and their correlation with testicular sperm retrieval outcomes. Materials and Methods: We analyzed 37 TIF samples, including 5 from men with obstructive azoospermia (OA) and 32 from men with non-obstructive azoospermia (NOA). Liquid chromatography with tandem mass spectrometry quantified testosterone and precursor levels. Comparative assessments of the outcomes of testicular sperm retrieval were performed between the OA and NOA groups as well as among men with NOA. Results: Men with NOA who had not undergone hormone treatment exhibited significantly higher intratesticular concentrations of testosterone (median 1,528.1 vs. 207.5 ng/mL), androstenedione (median 10.6 vs. 1.9 ng/mL), and 17-OH progesterone (median 13.0 vs. 1.8 ng/mL) than men diagnosed with OA. Notably, in the subgroup of patients with NOA subjected to medical treatment, men with successful sperm retrieval had significantly reduced levels of androstenedione (median androstenedione 5.7 vs. 18.5 ng/mL, p=0.004). Upon a more detailed analysis of these men who underwent hormone manipulation treatment, the testosterone/androstenedione ratio (indicative of HSD17B3 enzyme activity) was markedly increased in men with successful sperm retrieval (median: 365.8 vs. 165.0, p=0.008) compared with individuals with NOA who had unsuccessful sperm recovery. Furthermore, within the subset of men with NOA who did not undergo medical treatment before microdissection testicular sperm extraction but achieved successful sperm retrieval, the ratio of 17-OH progesterone/progesterone (indicative of CYP17A1 activity) was substantially higher. Conclusions The study suggests distinct testosterone biosynthesis pathways in men with compromised spermatogenesis and those with normal spermatogenesis. Among NOA men with successful retrieval after hormone optimization therapy, there was decreased androstenedione and increased HSD17B3 enzyme activity. These findings have diagnostic and therapeutic implications for the future.

Purpose: The study aimed to comprehensively analyze testosterone and precursor concentrations in the testicular interstitial fluid (TIF) of men with azoospermia, exploring their significance in the testicular microenvironment and their correlation with testicular sperm retrieval outcomes. Materials and Methods: We analyzed 37 TIF samples, including 5 from men with obstructive azoospermia (OA) and 32 from men with non-obstructive azoospermia (NOA). Liquid chromatography with tandem mass spectrometry quantified testosterone and precursor levels. Comparative assessments of the outcomes of testicular sperm retrieval were performed between the OA and NOA groups as well as among men with NOA. Results: Men with NOA who had not undergone hormone treatment exhibited significantly higher intratesticular concentrations of testosterone (median 1,528.1 vs. 207.5 ng/mL), androstenedione (median 10.6 vs. 1.9 ng/mL), and 17-OH progesterone (median 13.0 vs. 1.8 ng/mL) than men diagnosed with OA. Notably, in the subgroup of patients with NOA subjected to medical treatment, men with successful sperm retrieval had significantly reduced levels of androstenedione (median androstenedione 5.7 vs. 18.5 ng/mL, p=0.004). Upon a more detailed analysis of these men who underwent hormone manipulation treatment, the testosterone/androstenedione ratio (indicative of HSD17B3 enzyme activity) was markedly increased in men with successful sperm retrieval (median: 365.8 vs. 165.0, p=0.008) compared with individuals with NOA who had unsuccessful sperm recovery. Furthermore, within the subset of men with NOA who did not undergo medical treatment before microdissection testicular sperm extraction but achieved successful sperm retrieval, the ratio of 17-OH progesterone/progesterone (indicative of CYP17A1 activity) was substantially higher. Conclusions The study suggests distinct testosterone biosynthesis pathways in men with compromised spermatogenesis and those with normal spermatogenesis. Among NOA men with successful retrieval after hormone optimization therapy, there was decreased androstenedione and increased HSD17B3 enzyme activity. These findings have diagnostic and therapeutic implications for the future.

Objective To analyze the risk factors associated with the occurrence of rectal neuroendocrine tumors (RNETs) and construct a risk prediction model. Methods Clinical data of patients who underwent electronic colonoscopy were collected. The clinical information on patients with and without RNETs were compared, and potential risk factors for RNETs were identified. Binary logistic regression was performed to analyze the relevant risk factors and construct a risk prediction model. Results Among 164 patients, 66 were diagnosed with RNETs, and 98 who did not have such a condition were randomly selected. Univariate logistic regression analysis revealed that age, fatty liver, anxiety and depression, total cholesterol, triglyceride levels, and carcinoembryonic antigen (CEA) were significant factors influencing the occurrence of RNETs (P<0.05). Multivariate logistic regression analysis identified age (P=0.015), anxiety and depression (P=0.031), cholesterol level (P=0.009), fatty liver (P=0.001), and CEA (P<0.001) as independent risk factors for RNETs. The participants were randomly divided into training and test sets at a 7:3 ratio. The training set was used to construct a nomogram-based risk prediction model, and the testing set was used for internal validation. The area under the curve values for the training and testing sets were 0.843 and 0.772, respectively (P>0.05). These findings indicate a good discriminative performance. The calibration curves for the training and testing sets were in good agreement with the 45° standard line, which suggests that the predicted probabilities were consistent with the actual outcomes. Decision curve analysis showed that the model provided a high net benefit within a threshold range of 0.2 to 0.7 for clinical decision making. Conclusion Young age, fatty liver, high CEA levels, high cholesterol levels, and anxiety and depression are independent risk factors for RNETs. The nomogram model constructed based on these risk factors exhibits a strong capability to predict the occurrence of RNETs, and clinical intervention can be considered based on the predicted probability values.

Optical imaging is highly valued for its superior temporal and spatial resolution. This is particularly important in near-infrared II (NIR-II, 1 000-3 000 nm) imaging, which offers advantages such as reduced tissue absorption, minimal scattering, and low autofluorescence. These characteristics make NIR-II imaging especially suitable for deep tissue visualization, where high contrast and minimal background interference are critical for accurate diagnosis and monitoring. Currently, inorganic fluorescent probes—such as carbon nanotubes, rare earth nanoparticles, and quantum dots—offer high brightness and stability. However, they are hindered by ambiguous structures, larger sizes, and potential accumulation toxicity in vivo. In contrast, organic fluorescent probes, including small molecules and polymers, demonstrate higher biocompatibility but are limited by shorter emission wavelengths, lower quantum yields, and reduced stability. Recently, gold clusters have emerged as a promising class of nanomaterials with potential applications in biocatalysis, fluorescence sensing, biological imaging, and more. Water-soluble gold clusters are particularly attractive as fluorescent probes due to their remarkable optical properties, including strong photoluminescence, large Stokes shifts, and excellent photostability. Furthermore, their outstanding biocompatibility—attributed to good aqueous stability, ultra-small hydrodynamic size, and high renal clearance efficiency—makes them especially suitable for biomedical applications. Gold clusters hold significant potential for NIR-II fluorescence imaging. Atomic-precision gold clusters, typically composed of tens to hundreds of gold atoms and measuring only a few nanometers in diameter, possess well-defined three-dimensional structures and clear spatial coordination. This atomic-level precision enables fine-tuned structural regulation, further enhancing their fluorescence properties. Variations in cluster size, surface ligands, and alloying elements can result in distinct physicochemical characteristics. The incorporation of different atoms can modulate the atomic and electronic structures of gold clusters, while diverse ligands can influence surface polarity and steric hindrance. As such, strategies like alloying and ligand engineering are effective in enhancing both fluorescence and catalytic performance, thereby meeting a broader range of clinical needs. In recent years, gold clusters have attracted growing attention in the biomedical field. Their application in NIR-II imaging has led to significant progress in vascular, organ, and tumor imaging. The resulting high-resolution, high signal-to-noise imaging provides powerful tools for clinical diagnostics. Moreover, biologically active gold clusters can aid in drug delivery and disease diagnosis and treatment, offering new opportunities for clinical therapeutics. Despite the notable achievements in fundamental research and clinical translation, further studies are required to address challenges related to the standardized synthesis and complex metabolic behavior of gold clusters. Resolving these issues will help accelerate their clinical adoption and broaden their biomedical applications.