ObjectiveTo investigate the mechanism of Naoxintong capsules on ischemia-reperfusion （I/R） injury in rats based on the changes of pericytes mediated by Ras homolog family member A （RHOA）/Rho-associated coiled-coil containing protein kinase 1 （ROCK1） pathway. MethodsNinety rats （15 rats for each group） were randomly divided into a sham operation group， a model group， a positive control group receiving Ginkgo biloba extract （21.6 mg·kg^-1）， and groups receiving Naoxintong capsules at low， medium， and high doses of 55， 110， and 220 mg·kg^-1 （NXT-L， NXT-M， and NXT-H groups）， respectively. Except for those in the sham operation group， all rats were subjected to transient middle cerebral artery occlusion （tMCAO） to establish the experiment model. Nerve function was assessed using a neurological function score. Cerebral blood flow was detected using a laser speckle contrast imager， and the cerebral infarction rate was calculated using 2，3，5-Triphenyl tetrazolium chloride （TTC） staining. Pathological changes were observed by hematoxylin-eosin （HE） staining and Nissl staining， while pericyte morphology was observed via transmission electron microscopy. Blood-brain barrier destruction was observed by Evans blue staining. Albumin and ischemia-modified albumin levels were measured using assay kits. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） and Western blot were used to detect the mRNA and protein expression levels of RHOA， ROCK1， platelet-derived growth factor receptor β （PDGFRB）， α-smooth muscle actin （α-SMA）， tight junction protein （ZO-1）， matrix metalloproteinase-2 （MMP-2）， and matrix metalloproteinase-9 （MMP-9）. ResultsCompared with the sham operation group， the model group exhibited decreased neurological function scores， higher percentage reduction in blood flow， and increased cerebral infarction rates （P<0.01）. Additionally， cortical neuronal nucleus shrinkage， edema， a decreased number of Nissl bodies， reduced pericyte area， elevated albumin content in the cortex （P<0.05）， and increased ischemic modified albumin levels （P<0.01） were observed. The mRNA and protein expression levels of RHOA， ROCK1， PDGFRB， α-SMA， MMP-2， and MMP-9 were increased （P<0.01）， while those of ZO-1 were decreased. Compared with the model group， all treatment groups showed improved neurological function scores， lower percentage reduction in blood flow， reduced cerebral infarction rates （P<0.01）， alleviated cortical histological changes， increased number of Nissl bodies， expanded pericyte area， decreased albumin content in the cortex， and reduced ischemia-modified albumin levels （P<0.01）. The mRNA and protein expression levels of RHOA， ROCK1， PDGFRB， α-SMA， MMP-2， and MMP-9 were decreased （P<0.01）， while those of ZO-1 were increased. Among the treatment groups， the NXT-M group showed the most pronounced improvement in cerebral I/R injury. ConclusionNaoxintong capsules can restore cerebral blood supply， reduce microcirculation disturbance， and protect blood-brain barrier in rats with I/R injury. Its mechanism of action may be related to the inhibition of the RHOA/ROCK1 signaling pathway and reduced pericyte contraction.

ObjectiveTo investigate the mechanism of Naoxintong capsules on ischemia-reperfusion （I/R） injury in rats based on the changes of pericytes mediated by Ras homolog family member A （RHOA）/Rho-associated coiled-coil containing protein kinase 1 （ROCK1） pathway. MethodsNinety rats （15 rats for each group） were randomly divided into a sham operation group， a model group， a positive control group receiving Ginkgo biloba extract （21.6 mg·kg^-1）， and groups receiving Naoxintong capsules at low， medium， and high doses of 55， 110， and 220 mg·kg^-1 （NXT-L， NXT-M， and NXT-H groups）， respectively. Except for those in the sham operation group， all rats were subjected to transient middle cerebral artery occlusion （tMCAO） to establish the experiment model. Nerve function was assessed using a neurological function score. Cerebral blood flow was detected using a laser speckle contrast imager， and the cerebral infarction rate was calculated using 2，3，5-Triphenyl tetrazolium chloride （TTC） staining. Pathological changes were observed by hematoxylin-eosin （HE） staining and Nissl staining， while pericyte morphology was observed via transmission electron microscopy. Blood-brain barrier destruction was observed by Evans blue staining. Albumin and ischemia-modified albumin levels were measured using assay kits. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） and Western blot were used to detect the mRNA and protein expression levels of RHOA， ROCK1， platelet-derived growth factor receptor β （PDGFRB）， α-smooth muscle actin （α-SMA）， tight junction protein （ZO-1）， matrix metalloproteinase-2 （MMP-2）， and matrix metalloproteinase-9 （MMP-9）. ResultsCompared with the sham operation group， the model group exhibited decreased neurological function scores， higher percentage reduction in blood flow， and increased cerebral infarction rates （P<0.01）. Additionally， cortical neuronal nucleus shrinkage， edema， a decreased number of Nissl bodies， reduced pericyte area， elevated albumin content in the cortex （P<0.05）， and increased ischemic modified albumin levels （P<0.01） were observed. The mRNA and protein expression levels of RHOA， ROCK1， PDGFRB， α-SMA， MMP-2， and MMP-9 were increased （P<0.01）， while those of ZO-1 were decreased. Compared with the model group， all treatment groups showed improved neurological function scores， lower percentage reduction in blood flow， reduced cerebral infarction rates （P<0.01）， alleviated cortical histological changes， increased number of Nissl bodies， expanded pericyte area， decreased albumin content in the cortex， and reduced ischemia-modified albumin levels （P<0.01）. The mRNA and protein expression levels of RHOA， ROCK1， PDGFRB， α-SMA， MMP-2， and MMP-9 were decreased （P<0.01）， while those of ZO-1 were increased. Among the treatment groups， the NXT-M group showed the most pronounced improvement in cerebral I/R injury. ConclusionNaoxintong capsules can restore cerebral blood supply， reduce microcirculation disturbance， and protect blood-brain barrier in rats with I/R injury. Its mechanism of action may be related to the inhibition of the RHOA/ROCK1 signaling pathway and reduced pericyte contraction.

Background Personal protection is crucial for reducing the risk of zoonotic pathogen infection among livestock workers. Investigating the current status of its implementation and associated influencing factors can provide empirical evidence for developing more effective intervention measures. Objective To investigate the current status of personal protection implementation among livestock workers in Xinjiang, China and its influencing factors, providing a reference for formulating targeted intervention measures. Methods This study was conducted in Bayingolin Mongol Autonomous Prefecture, Kashgar region, and the First and Eighth Divisions of Xinjiang Production and Construction Corps. We selected large-scale cattle and sheep farms, cooperatives, individual livestock households, livestock trading markets, slaughterhouses, and retail markets. Using cluster sampling, we recruited all livestock workers (1074 participants) at sampled sites. During the period from April to July 2024, we conducted face-to-face surveys with a self-designed questionnaire among livestock workers, collecting general demographic information, occupational exposure history, and information related to the use of personal protective equipment, resulting in 939 valid questionnaires. EpiData 3.1 was used for data entry and SPSS 26.0 for statistical analysis. We employed logistic regression to compare the implementation of personal protection among workers by selected categories. Results Among the study subjects, there were 300 workers from large-scale farms (31.95%) and 583 self-employed livestock farmers (62.09%). The sample included 600 males (63.90%) and 339 females (36.10%). The majority of the study subjects was farmers, breeders, or aged 18-60 years (87.75%), auxiliary workers (87.97%) and had an education level of junior high school or below (81.36%). The proportion of workers who consistently and correctly implemented all five personal protective measures (washing hands after work, wearing gloves, wearing masks, wearing dedicated work clothes, and using rubber boots) was 35.14% (330/939). The implementation rates for these five protective measures were 93.61% (879/939), 58.68% (551/939), 57.93% (544/939), 46.01% (432/939), and 42.81% (402/939), respectively. There were statistically significant differences in the implementation rates of differen personal protective measures among the workers by occupation and education level (P<0.05). Among them, workers with lower education levels had lower implementation rates for various protective measures. The results of logistic regression indicated that, compared to male workers, female workers (OR=2.26, 95%CI: 1.68, 3.04) showed a higher rate of non-standard implementation of personal protection. Using the age group of 18 to less than 36 years as a reference, those aged 36 to less than 60 years (OR=1.82, 95%CI: 1.33, 2.50) and 60 years or older (OR=4.45, 95%CI: 2.56, 7.73) reported higher rates of non-standard implementation of personal protection. Compared to those with an education level of primary school or below, those with a junior high school education (OR=0.64, 95%CI: 0.47, 0.88) and a high school education or above (OR=0.13, 95%CI: 0.19, 0.29) showed lower rates of non-standard implementation of personal protection. Compared to farmers, veterinarians (OR=0.03, 95%CI: 0.02, 0.07) reported the lowest rate of non-standard implementation of personal protection, followed by auxiliary workers (OR=0.08, 95%CI: 0.05, 0.12), breeders (OR=0.10, 95%CI: 0.07, 0.15), and other occupational groups (OR=0.28, 95%CI: 0.15, 0.52). Using large-scale farms as a reference, self-employed farmers (OR=13.5, 95%CI: 9.65, 18.88) reported a higher rate of non-standard implementation of personal protection, followed by workers from other workplaces (OR=3.63, 95%CI: 2.01, 6.54). Conclusion The implementation of personal protective measures among livestock workers in Xinjiang is generally satisfactory. However, significant disparities in the execution of these measures exist among different types of workers, indicating the need to enhance occupational health promotion to reduce the risk of zoonotic pathogen infection among the workers.

Background Animal farming may affect the structure and diversity of gut microbiota of farm workers, but it needs more studies to provide solid evidence. Objective To analyze the diversity characteristics of gut microbiota in dairy farm workers, dairy cows, and the control population (non-animal contact occupational group), and to assess the impact of dairy farming on the gut microbiota of workers. Methods The 16S rRNA full-length amplicon sequencing technology was used to sequence 60 fecal samples from dairy farm workers, 89 from dairy cows, and 50 from the general population. The gut microbiota structure characteristics, including operational taxonomic units (OTUs), alpha diversity, beta diversity, and the composition of species at the phylum, family, and genus levels were analyzed. The differences in gut microbiota among the three groups of samples were compared to explore the impact of occupational exposure on the gut microbiota structure of dairy farm workers. Results A total of 50478 OTUs were identified in the gut microbiota of farm workers, dairy cows, and the general population, with 23613, 42723, and 16592 OTUs, respectively. The number of shared OTUs between the dairy cows and the general population was 12674 (27.17%), between the general population and the farm workers was 10099 (33.54%), and between the dairy cows and the farm workers was 17690 (36.36%). Compared with the general population, the farm workers and dairy cows showed more shared gut microbiota (P<0.01). The abundance of Firmicutes in the gut of the farm workers was higher than that of the general population (P<0.01), while Actinobacteriota and Proteobacteria were the opposite (P<0.01). The alpha diversity of gut microbiota in the farm workers was different from that of the general population. The ACE index of the farm workers was slightly lower than that of the general population and much lower than that of dairy cows (P<0.05), while their Shannon index was higher than that of the general population but lower than that of dairy cows (P<0.01). The linear discriminant analysis effect size (LefSe) showed that the abundances of Lachnospiraceae and Ruminococcaceae in the gut microbiota of the farm workers were significantly higher than those of the general population, while Streptococcaceae, Lactobacillaceae, Bifidobacteriaceae, Enterobacteriaceae, and Erysipelatoclostridiaceae were lower than those of the general population. Conclusion The dairy farm workers shares a certain proportion of common bacterial communities with dairy cows. Dairy farming operations can affect the structure and diversity of the gut microbiota of workers by increasing the abundances of Lachnospiraceae and Ruminococcaceae, while decreasing the abundances of Streptococcaceae, Lactobacillaceae, Bifidobacteriaceae, Enterobacteriaceae, and Erysipelatoclostridiaceae. The study results provide reference data for further exploring the cross-host transmission of pathogens related to occupational exposure in dairy farming.

Pure drug nanomedicines (PDNs) encompass active pharmaceutical ingredients (APIs), including macromolecules, biological compounds, and functional components. They overcome research barriers and conversion thresholds associated with nanocarriers, offering advantages such as high drug loading capacity, synergistic treatment effects, and environmentally friendly production methods. This review provides a comprehensive overview of the latest advancements in PDNs, focusing on their essential components, design theories, and manufacturing techniques. The physicochemical properties and in vivo behaviors of PDNs are thoroughly analyzed to gain an in-depth understanding of their systematic characteristics. The review introduces currently approved PDN products and further explores the opportunities and challenges in expanding their depth and breadth of application. Drug nanocrystals, drug-drug cocrystals (DDCs), antibody-drug conjugates (ADCs), and nanobodies represent the successful commercialization and widespread utilization of PDNs across various disease domains. Self-assembled pure drug nanoparticles (SAPDNPs), a next-generation product, still require extensive translational research. Challenges persist in transitioning from laboratory-scale production to mass manufacturing and overcoming the conversion threshold from laboratory findings to clinical applications.
Nanomedicine ; Humans ; Nanoparticles/chemistry* ; Pharmaceutical Preparations/chemistry* ; Animals ; Drug Carriers/chemistry*

This article reported a patient who initially presented with insomnia complaints and was subsequently diagnosed with severe obstructive sleep apnea （OSA） on polysomnography （PSG）. The patient tried continuous positive airway pressure （CPAP）but gave up because wear the ventilator made it more difficult to fall asleep. Then the patient only received group cognitive behavioral therapy for insomnia （CBT-I）， which not only alleviated insomnia severity but also promoted severe OSA into mild status. Such case suggested that， firstly， due to the high comorbidity of insomnia and OSA， evaluation of OSA should be considered a part worth enough attention of the clinical diagnosis and treatment of insomnia patients. Secondly， by relieving insomnia， CBT-I can alleviate both nocturnal apnea and daytime somnolence in patients with comorbid insomnia and sleep apnoea （COMISA）， so the application of CBT-I should be emphasized in the treatment of such patients. ［Funded by the Central Government-guided Local Science and Technology Development Fund Project （number， 2022ZY0028）］

Objective:To standardize the management of auditory hallucination symptoms in inpatients with mental illness and develop an expert consensus on the management of auditory hallucinations in hospitalized psychiatric patients.Methods:From March 2023 to July 2023, the Mental Health Committee of the Chinese Nursing Association focused on the key issues in the management of auditory hallucinations symptoms in inpatients with mental illness, based on clinical practice, using literature analysis combined with the work experience of mental health experts, and formed the first draft of the expert consensus on the management of auditory hallucinations in inpatients with mental illness (hereinafter referred to as the consensus). Through 3 rounds of expert consultation and 3 rounds of expert demonstration meeting, the draft was adjusted, revised, and improved.Results:37 experts were included in the Delphi expert consultation, 1 male and 36 females with 39-67(51.48 ± 6.61) years old. The positive coefficients of experts in 3 rounds of Delphi expert consultations were all 100%, and the degrees of expert authority were 0.924, 0.938 and 0.949, respectively. The average importance value of each item was higher than 4.00, the variation coefficient of each item was less than 0.25. The Kendall harmony coefficient of the experts were 0.179, 0.195 and 0.198, respectively (all P<0.05). There were 15, 12, 12 experts in the first, seeond, third rounds of expert demonstration meeting. Finally, a consensus was reached on the recommendation of 4 parts, included auditory hallucination assessment, management format, symptom management implementation, and precautions. Conclusions:The consensus covers all parts of the management of auditory hallucination symptoms in hospitalized patients with mental disorders, which is practical and scientific. It is helpful to guide mental health professionals to standardize the management of auditory hallucination symptoms, improve the quality of nursing and ensure the safety of patients.

Objective:To investigate the efficacy of sintilimab combined with paclitaxel and docetaxel in the treatment of advanced non-small cell lung cancer (NSCLC).Methods:Prospective cohort study was performed. A total of 90 patients with advanced NSCLC receiving second-line treatment in Baotou Cancer Hospital from October 2019 to October 2022 were prospectively selected. All patients were divided into the study group (sintilimab combined with paclitaxel and docetaxel as second-line treatment, 45 cases) and the control group (paclitaxel or docetaxel alone, 45 cases) according to random number table method. The short-term efficacy, serum cytokine levels, quality of life and T-cell subsets of the two groups were compared. The survival of patients within 6 months was followed up. Kaplan-Meier method was used to analyze the overall survival (OS) of both groups, and log-rank test was used to make comparison among groups.Results:There were 25 males (55.56%) in the study group with the age of (63±5) years and 28 males (62.22%) in the control group with the age of (65±6) years. There were no statistically significant differences in the gender, age, Eastern Cooperative Oncology Group scores, the body mass (all P>0.05). The total effective rate was 88.89% (40/45) in the study group and 71.11% (32/45) in the control group, and the difference was statistically significant ( χ2 = 4.44, P = 0.035). The levels of serum vascular endothelial growth factor (VEGF) and carbohydrate antigen 125 (CA125) of both groups after treatment were lower than those before treatment (all P<0.001); the levels of VEGF and CA125 in the study group after treatment were lower than those in the control group [VEGF: (223±15) pg/ml vs. (289±15) pg/ml, t=20.82, P<0.001;CA125: (23±6) ng/ml vs. (75±4) ng/ml, t=51.28, P<0.001].Quality of life scale score, Karnofsky score of both groups after treatment were higher than those before treatment (all P<0.05); quality of life scale score and Karnofsky score in the study group after treatment were higher than those in the control group [quality of life scale score: (63±6) scores vs. (51±5) scores, t=10.29, P<0.001; Karnofsky score: (80.5±5.7) scores vs.(78.8±3.7) scores, t=1.70, P=0.041]. T-cell subsets indicators of both groups after treatment were higher than those before treatment (all P<0.001). T-cell subsets indicators in the study group after treatment were higher than those in the control group [CD3 + cell proportion: (68±5)% vs. (65±5)%, t=2.52, P = 0.014; CD4 + cell proportion:(42.5±1.7)% vs. (36.5±3.7)%, t=9.91, P<0.001;CD4 +/CD8 +: 1.78±0.54 vs. 1.46±0.27, t=3.56, P<0.001]. There was no significant difference in the incidence of adverse reactions between the two groups [11.11% (5/45) vs. 15.55% (7/45), χ2=0.39, P=0.534]. The follow-up time was 6 months. The OS in the study group was better than that in the control group ( χ2=3.86, P = 0.044). Conclusions:Sintilimab combined with taxoid chemotherapy drugs is effective in the second-line treatment of advanced NSCLC, and it improves immune function and shows a favorable safety.

Inducing the degradation of KRAS represents a novel strategy to combat cancers with KRAS mutation. In this study, we identify ubiquitin-specific protease 2 (USP2) as a novel deubiquitinating enzyme of KRAS in multiple myeloma (MM). Specifically, we demonstrate that gambogic acid (GA) forms a covalent bond with the cysteine 284 residue of USP2 through an allosteric pocket, inhibiting its deubiquitinating activity. Inactivation or knockdown of USP2 leads to the degradation of KRAS, resulting in the suppression of MM cell proliferation in vitro and in vivo. Conversely, overexpressing USP2 stabilizes KRAS and partially abrogates GA-induced apoptosis in MM cells. Furthermore, elevated USP2 levels may be associated with poorer prognoses in MM patients. These findings highlight the potential of the USP2/KRAS axis as a therapeutic target in MM, suggesting that strategically inducing KRAS degradation via USP2 inhibition could be a promising approach for treating cancers with KRAS mutations.

The use of checkpoint-blockade antibodies is still restricted in several malignancies due to the modest efficacy, despite considerable success in anti-tumor immunotherapy. The poor response of cancer cells to immune destruction is an essential contributor to the failure of checkpoint therapy. We hypothesized that combining checkpoint therapy with natural-product chemosensitizer could enhance immune response. Herein, a targeted diterpenoid derivative was integrated with the checkpoint blockade (anti-CTLA-4) to improve immunotherapy using thermosensitive liposomes as carriers. In vivo, the liposomes enabled the co-delivery of the two drug payloads into the tumor. Consequently, the regulatory T cell proliferation was restrained, the cytotoxic T cell infiltration was enhanced, and the profound immunotherapeutic effect was achieved. In addition, the immunotherapeutic effect of another clinically used checkpoint antibody, anti-PD-1, also benefited from the diterpenoid derivative. Of note, our mechanism study revealed that the targeted diterpenoid derivative increased the sensitivity of cancer cells to immune attack via THBS1 downregulation and the resultant destruction of THBS1-CD47 interaction. Collectively, co-delivering THBS1 inhibitor and checkpoint blockade is promising to boost cancer immunotherapy. We first time discovered that THBS1 suppression could strengthen checkpoint therapy.