In order to explore the possible role and molecular mechanism of the combined action of leech and bear bile in liver and gallbladder diseases, this study first used network pharmacology methods to screen the components and targets of leech and bear bile, as well as the related target genes of liver and gallbladder diseases. The selected key genes were subjected to interaction network and GO/KEGG enrichment analysis. Then, using sodium oleate induced HepG2 cell lipid deposition model and DL-ethionine induced mouse fatty liver model, the activity of leech and bear bile alone and in combination in reducing liver fat was evaluated in vitro and in vivo, and the expression of key pathway related proteins suggested by network pharmacology was detected by Western blot. The results of network pharmacology analysis showed that the active ingredients of leech and bear bile have 295 intersecting targets with liver and gallbladder related diseases, involving more than 200 signaling pathways, including the PI3K/Akt signaling pathway and phospholipase D signaling pathway closely related to glucose and lipid metabolism. The results of in vitro validation experiments showed that both leech and bear bile, alone and in combination, can significantly inhibit the lipid deposition induced by sodium oleate in human liver cells, reduce the triacylglycerol level in cell culture supernatant, and inhibit the lipid content in liver cells. The observation results of Nile red staining confocal microscopy showed that the combination of leech and bear bile had better activity in reducing lipid deposition in liver cells compared to using them alone. In a mouse fatty liver model, the combination of leech and bear bile can better reduce elevated organ indices, blood lipids, and liver lipid levels, as well as lower the levels of serum liver injury biomarkers. The animals used in this experiment and related disposal meet the requirements of animal welfare. Before the experiment, it was reviewed and approved by IACUC, Institute of Materia Medica, Chinese Academy of Medical Sciences. The Western blot experiment results showed that the combination of leech and bear bile can significantly upregulate the expression levels of p-PI3K and p-Akt proteins, and increase the p-PI3K/PI3K and p-Akt/Akt ratios, which is consistent with the predicted results of network pharmacology. The combination of leech and bear bile has great potential for treating fatty liver disease, and activating the PI3K/Akt pathway may be one of the important mechanisms for reducing lipid deposition in liver cells.

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.

Background Kurtosis reflecting noise's temporal structure is an effective metric for evaluating noise-induced hearing loss (NIHL), and its threshold is still unclear. Objective To explore the energy range of kurtosis and the threshold of NIHL induced by kurtosis in this energy rangeMethods Using cross-sectional design, 4631 noise-exposed workers in manufacturing industry were selected. The hearing loss and noise exposure data of each worker were collected. Logistic regression model was used to establish the dose-response relationship between noise exposure and hearing loss and estimate the range of energy effects. Restricted cubic spline model was utilized to analyze the dose-response relationship curves of kurtosis to noise-induced hearing loss (NIHI) and high-frequency noise-induced hearing loss (HFNIHL) under different 8 h equivalent sound levels (L_{EX,8 h}), as well as to estimate the kurtosis effect threshold. Results The logistic regression model analysis showed that the prevalence of NIHI and HFNIHL increased significantly with increase of L_{EX,8 h} for steady noise; when L_{EX,8 h} of non-steady noise was 80-100 dB(A), the risk of hearing loss increased with an increase in kurtosis (P<0.05). The restricted cubic spline model showed that when L_{EX,8 h} of non-steady noise was 0-80 dB(A) or >100 dB(A), there was no significant relationship between kurtosis and NIHI or HFNIHL. When L_{EX,8 h} was 80-100 dB(A), there was a significant nonlinear dose-response relationship between kurtosis and NIHL or HFNIHL (P <0.001), and kurtosis > 28.08 exerted effect in elevating NIHI or HFNIHL. Conclusion The effect threshold of kurtosis on NIHL is 28.08 when non-steady noise levels are in the range of 80-100 dB(A). The effect threshold of kurtosis needs further verification.

Objective To systematically evaluate the radiation impact of radioactive sources used in online elemental analyzers in cement enterprises on the surrounding environment, and to provide a scientific basis for radiation monitoring and safety management at the application sites of this type of radioactive sources. Methods A statistical analysis was conducted on 15 cement enterprises in Guangxi Province using online elemental analyzers with ²⁵²Cf as the radioactive source. On-site investigation of radiation safety management and on-site monitoring of radiation environment were performed, followed by an evaluation based on the collected data. Results Although the gamma radiation ambient dose equivalent rate and neutron ambient dose equivalent rate increased around the sites using online elemental analyzers with ²⁵²Cf as the radioactive source, they all met the requirements of the Radiological Health Protection Requirements for Instruments with Sealed Sources (GBZ 125—2009). Conclusion Under the current usage and management conditions, the application of this type of radioactive sources has controllable radiation impact on the surrounding environment, and will not pose a threat to public health and environmental safety. However, continuous strengthening of radiation safety management measures and regular radiation monitoring work are still needed to ensure the safe use of radioactive sources, further reducing potential radiation risks and providing strong guarantees for the safe application of radioactive sources in online elemental analyzers in cement enterprises.

Objective To explore the medication rules of Professor Hua Baojin in the treatment of subsolid pulmonary nodules through retrospective analysis and data mining techniques. Methods The prescriptions of patients with subsolid pulmonary nodules who were diagnosed and treated by Professor Hua Baojin at Guang’anmen Hospital of the Chinese Academy of Chinese Medical Sciences from January 1, 2021 to December 31, 2024 were retrospectively collected. Data were imported into the Ancient and Modern Medical Case Cloud Platform for analysis of drug frequency, four natures and five flavors, meridian tropism, drug association, and hierarchical clustering. Results A total of 455 prescriptions were included, containing 205 kinds of traditional Chinese medicines, with a total frequency of 12048 times. Fifty-seven commonly used drugs were screened out, among which drugs with high frequencies included astragalus membranaceus (raw) and hawthorn fruit (charred). The nature of the drugs was mainly warm, cold, and neutral. The flavor of the drugs was mostly sweet, bitter, and pungent. The meridians they belonged to mainly included the lung, spleen, and liver meridians. Their efficacy was mainly tonifying deficiency, clearing heat, resolving phlegm, and relieving cough and asthma. Association analysis obtained 19 pairs of drug combinations, 21 groups of three-drug combinations, and four groups of four-drug combinations. Hierarchical clustering obtained 10 groups of drug combinations. Conclusion On the basis of the core pathogenesis of subsolid pulmonary nodule, Professor Hua applies the theory of regulating qi and detoxifying; regulating the qi of the liver, spleen, and lung; and detoxifying the toxins of phlegm and blood stasis, providing valuable experience for the clinical treatment of SSN.

OBJECTIVE To analyze the prevalence of potentially inappropriate medication （PIM） in elderly patients with femoral neck fractures at admission and compare the concordance of 3 evaluation criteria. METHODS A retrospective study was conducted to review the data of elderly patients with femoral neck fractures admitted to the Department of Orthopedics in Northern Jiangsu People’s Hospital from July 2022 to June 2023. The PIMs were identified according to the Criteria of Potentially Inappropriate Medications for Older Adults in China：2017 edition （hereinafter referred to as Chinese criteria）， American Geriatrics Society 2023 Updated AGS Beers Criteria® for Potentially Inappropriate Medication in Older Adults （hereinafter referred to as 2023 Beers criteria）， third version criteria for screening tool of older people’s prescriptions for potentially inappropriate medication （hereinafter referred to as STOPP criteria version 3）. The concordance of the 3 evaluation criteria was compared by using Kappa statistics. RESULTS A total of 246 patients were included in this study； 49 patients （19.92%） with 77 PIMs were detected by the Chinese criteria， 64 patients （26.02%） with 118 PIMs were detected by the 2023 Beers criteria， and 41 patients （16.67%） with 67 PIMs were detected by the STOPP criteria version 3； 22 patients met all three criteria simultaneously. The concordance among the three criteria showed moderate agreement （0.417≤Kappa≤0.486） when compared in pairs. CONCLUSIONS There are certain differences in the PIM evaluated by the three criteria， but the prevalence of PIMs is below 30% according to the different H202134） criteria. Benzodiazepines， antipsychotics， antidepressants， and other drugs may increase the risk of patients falling again.

Hepatic steatosis can be observed in chronic liver diseases of different etiologies. The main predisposing factors for hepatic steatosis include chronic viral hepatitis， cholestatic liver disease， alcoholic liver disease， and nonalcoholic fatty liver disease. Simple fatty liver disease is the initial manifestation of hepatic steatosis， followed by steatohepatitis， liver fibrosis， liver cirrhosis， and even hepatocellular carcinoma. With the development of medical imaging technology， magnetic resonance imaging-proton density fat fraction （MRI-PDFF） has been widely used in the diagnosis of fatty liver disease （FLD） in clinical practice. MRI-PDFF is gradually becoming the gold standard for the noninvasive diagnosis of FLD due to its high accuracy and good repeatability. This article reviews the clinical application of MRI-PDFF in liver fat quantification and related research advances.

Sepsis is a condition characterized by organ dysfunction resulting from the systemic inflammatory response triggered by an infection. Excessive inflammation and immunosuppression are intertwined, and severe cases may even develop into multiple organ failure. Studies have shown that indoleamine 2,3-dioxygenase 1-mediated tryptophan metabolism is involved in the occurrence and development of sepsis, and elevated plasma kynurenine levels and Kyn/Trp ratios are early indicators of sepsis development. In this paper, we provide a comprehensive summary of the role of IDO1 in the acute inflammatory phase of sepsis, late immunosuppression, and organ damage. This includes its regulation of inflammatory state, immune cell function, blood pressure, and other aspects. Additionally, we analyze preclinical studies on targeted IDO1 drugs. An in-depth understanding and study of IDO may help to understand the pathogenesis and clinical significance of sepsis and multiple organ damage from a new perspective and provide new research ideas for exploring its prevention and treatment methods.

This paper investigates the effect of myricetin (MYR) on renal fibrosis induced by unilateral ureteral obstruction (UUO) and common bile duct ligation (CBDL) in mice and its mechanism. The animal experiment has been approved by the Ethics Committee of China Pharmaceutical University (NO: 2022-10-020). Thirty-five ICR mice were divided into control, UUO, UUO+MYR, CBDL and CBDL+MYR groups. H&E and Masson staining were used to detect pathological changes in kidney tissues. Western blot (WB) was used to detect the expression of fibrosis-related proteins in renal tissue, and total superoxide dismutase (SOD) activity detection kit (WST-8) was used to detect the changes of total SOD in renal tissue of CBDL mice. In vitro, HK-2 cells and transforming growth factor beta 1 (TGF-β1, 10 ng·mL^-1) were used to induce fibrotic model, and high glucose (30 mmol·L^-1) was used to induce oxidative stress model, and then treated with different concentrations of MYR, WB was used to detect the expression of fibrosis and oxidative stress-related proteins, while NIH/3T3 cells were treated with different concentrations of MYR, and their effects on cell proliferation were detected by 5-bromo-2′-deoxyuridine (Brdu). The results showed that the renal lesions in UUO group and CBDL group were severe, collagen deposition was obvious, the expression of collagen-Ⅰ (COL-Ⅰ), α-smooth muscle actin (α-SMA), fibronectin (FN), vimentin and plasminogen activator inhibitor-1 (PAI-1) protein was up-regulated, and the activity of SOD enzyme in CBDL group was significantly decreased. MYR partly reversed the above changes after treatment. MYR inhibited the proliferation of NIH/3T3 cells but had no effect on the proliferation of HK-2 cells, and decreased the upregulation of PAI-1, FN and vimentin in HK-2 cells stimulated by TGF-β1. MYR can also up-regulate the down-regulation of nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) in HK-2 cells stimulated by high glucose. To sum up, MYR can improve renal fibrosis in vivo and in vitro, probably by inhibiting the proliferation of fibroblasts and activating Nrf2/HO-1 signal pathway to inhibit oxidative stress.

Objective To analyze the micronucleus rate of radiation workers and to provide accurate occupational health monitoring basis in radiation workers exposed to low-level ionizing radiation for a long time. Methods The radiation group consisted of 353 radiation workers who had been exposed to ionizing radiation during work, while the control group consisted of 41 radiation workers who had not yet been exposed to ionizing radiation before work. The cytokinesis-block micronucleus method was used to determine the micronucleus rate. Results The average micronucleus rate in the radiation group was significantly higher than that in the control group (t = −2.95, P < 0.05). In the radiation group, the micronucleus rate gradually increased with age, and the difference was statistically significant (F = 8.36, P < 0.05). The micronucleus rates of workers with > 10 and > 30 years of service were significantly higher than those of workers with < 10 years of service (χ² = −44.79, −60.47, P < 0.05). The micronucleus rate in females was significantly higher than that in males (t = 3.93, P < 0.05). The micronucleus rates in the diagnostic radiology group and the industrial detection group were significantly higher than that in the control group (t = 3.51, 3.65, P < 0.05). Conclusion The micronucleus rate has increased among the radiation workers exposed to low-level ionizing radiation for a long time. It is necessary to further strengthen occupational health monitoring and radiation protection education for radiation workers, especially the medical workers that constitute the largest population of radiation exposure workers.