Objective This study reports on the obligatory parasitism of water mites Arrenurus sp. on Anopheles messeae at the Manzhouli Port, Inner Mongolia, China. Methods Duing July 2024, a survey on the mosquito diversity was conducted at the Manzhouli Port. Captured mosquitoes and their ectoparasites were identified to species level. Results A total of 1840 adult mosquitoes were collected, representing species from three genera: Culex(Cx. modestus, Cx. pipiens pallens), Aedes(Ae. dorsalis, Ae. flavidorsalis, Ae. flavescens), and Anopheles (An. messeae). Among all the mosqutioes specimens,3 out of 150 captured An. messeae were found to carry ectoparasitic mites, with number of 2,4,27 mites separately. Morphological and molecular identification reached the same result as water mites(Hydrachnidiae, Hydracrina). COI gene sequence showed 94% similarity with the closest species Arrenurus truncatellus. Conlusions Literature review suggests water mites are host-specific parasitism of mosquito species and herein with the first record of Arrenurus sp. parasiting on An. Messeae in the most high-latitude region globally.

PURPOSE: To investigate the protective effect of sub-hypothermic mechanical perfusion combined with membrane lung oxygenation on ischemic hypoxic injury of yorkshire brain tissue caused by traumatic blood loss. METHODS: This article performed a random controlled trial. Brain tissue of 7 yorkshire was selected and divided into the sub-low temperature anterograde machine perfusion group (n = 4) and the blank control group (n = 3) using the random number table method. A yorkshire model of brain tissue injury induced by traumatic blood loss was established. Firstly, the perfusion temperature and blood oxygen saturation were monitored in real-time during the perfusion process. The number of red blood cells, hemoglobin content, NA⁺, K⁺, and Ca²⁺ ions concentrations and pH of the perfusate were detected. Following perfusion, we specifically examined the parietal lobe to assess its water content. The prefrontal cortex and hippocampus were then dissected for histological evaluation, allowing us to investigate potential regional differences in tissue injury. The blank control group was sampled directly before perfusion. All statistical analyses and graphs were performed using GraphPad Prism 8.0 Student t-test. All tests were two-sided, and p value of less than 0.05 was considered to indicate statistical significance. RESULTS: The contents of red blood cells and hemoglobin during perfusion were maintained at normal levels but more red blood cells were destroyed 3 h after the perfusion. The blood oxygen saturation of the perfusion group was maintained at 95% - 98%. NA⁺ and K⁺ concentrations were normal most of the time during perfusion but increased significantly at about 4 h. The Ca²⁺ concentration remained within the normal range at each period. Glucose levels were slightly higher than the baseline level. The pH of the perfusion solution was slightly lower at the beginning of perfusion, and then gradually increased to the normal level. The water content of brain tissue in the sub-low and docile perfusion group was 78.95% ± 0.39%, which was significantly higher than that in the control group (75.27% ± 0.55%, t = 10.49, p < 0.001), and the difference was statistically significant. Compared with the blank control group, the structure and morphology of pyramidal neurons in the prefrontal cortex and CA1 region of the hippocampal gyrus were similar, and their integrity was better. The structural integrity of granulosa neurons was destroyed and cell edema increased in the perfusion group compared with the blank control group. Immunofluorescence staining for glail fibrillary acidic protein and Iba1, markers of glial cells, revealed well-preserved cell structures in the perfusion group. While there were indications of abnormal cellular activity, the analysis showed no significant difference in axon thickness or integrity compared to the 1-h blank control group. CONCLUSIONS Mild hypothermic machine perfusion can improve ischemia and hypoxia injury of yorkshire brain tissue caused by traumatic blood loss and delay the necrosis and apoptosis of yorkshire brain tissue by continuous oxygen supply, maintaining ion homeostasis and reducing tissue metabolism level.
Animals ; Perfusion/methods* ; Disease Models, Animal ; Brain Injuries/etiology* ; Swine ; Male ; Hypothermia, Induced/methods*

Oral squamous cell carcinoma (OSCC) is the most common head and neck malignancy worldwide, accounting for more than 90% of all oral cancers, and is characterized by high invasiveness and poor long-term prognosis. Its etiology is multifactorial, involving tobacco use, alcohol consumption, and human papillomavirus (HPV) infection. Oral leukoplakia and erythroplakia are the main precancerous lesions lesions, with oral leukoplakia being the most common. Both OSCC and premalignant lesions are closely associated with aberrant activation of multiple signaling pathways. Post-translational modifications (such as ubiquitination and deubiquitination) play key roles in regulating these pathways by controlling protein stability and activity. Growing evidence indicates that dysregulated ubiquitination/deubiquitination can mediate OSCC initiation and progression via aberrant activation of signaling pathways. The ubiquitination/deubiquitination process mainly involves E3 ligases (E3s) that catalyze substrate ubiquitination, deubiquitinating enzymes (DUBs) that remove ubiquitin chains, and the 26S proteasome complex that degrades ubiquitinated substrates. Abnormal expression or mutation of E3s and DUBs can lead to altered stability of critical tumor-related proteins, thereby driving OSCC initiation and progression. Therefore, understanding the aberrantly activated signaling pathways in OSCC and the ubiquitination/deubiquitination mechanisms within these pathways will help elucidate the molecular mechanisms and improve OSCC treatment by targeting relevant components. Here, we summarize four aberrantly activated signaling pathways in OSCC―the PI3K/AKT/mTOR pathway, Wnt/β-catenin pathway, Hippo pathway, and canonical NF-κB pathway―and systematically review the regulatory mechanisms of ubiquitination/deubiquitination within these pathways, along with potential drug targets. PI3K/AKT/mTOR pathway is aberrantly activated in approximately 70% of OSCC cases. It is modulated by E3s (e.g., FBXW7 and NEDD4) and DUBs (e.g., USP7 and USP10): FBXW7 and USP10 inhibit signaling, while NEDD4 and USP7 potentiate it. Aberrant activation of the Wnt/β‑catenin pathway leads to β‑catenin nuclear translocation and induction of cell proliferation. This pathway is modulated by E3s (e.g., c-Cbl and RNF43) and DUBs (e.g., USP9X and USP20): c-Cbl and RNF43 inhibit signaling, while USP9X and USP20 potentiate it. Hippo pathway inactivation permits YAP/TAZ to enter the nucleus and promotes cancer cell metastasis. This pathway is modulated by E3s (e.g., CRL4^DCAF1 and SIAH2) and DUBs (e.g., USP1 and USP21): CRL4^DCAF1 and SIAH2 inhibit signaling, while USP1 and USP21 potentiate it. Persistent activation of the canonical NF-κB pathway is associated with an inflammatory microenvironment and chemotherapy resistance. This pathway is modulated by E3s (e.g., TRAF6 and LUBAC) and DUBs (e.g., A20 and CYLD): A20 and CYLD inhibit signaling, while TRAF6 and LUBAC potentiate it. Targeting these E3s and DUBs provides directions for OSCC drug research. Small-molecule inhibitors such as YCH2823 (a USP7 inhibitor), GSK2643943A (a USP20 inhibitor), and HOIPIN-8 (a LUBAC inhibitor) have shown promising antitumor activity in preclinical models; PROTAC molecules, by binding to surface sites of target proteins and recruiting E3s, achieve targeted ubiquitination and degradation of proteins insensitive to small-molecule inhibitors, for example, PU7-1-mediated USP7 degradation, offering new strategies to overcome traditional drug limitations. Currently, NX-1607 (a Cbl-b inhibitor) has entered phase I clinical trials, with preliminary results confirming its safety and antitumor activity. Future research on aberrant E3s and DUBs in OSCC and the development of highly specific inhibitors will be of great significance for OSCC precision therapy.

Objective:To evaluate the clinical equivalence between a domestic calcipotriol/betamethasone dipropionate ointment and the originator product in the treatment of stable plaque psoriasis.Methods:A multicenter, randomized, double-blind, three-arm, parallel-group, active- and placebo-controlled study was conducted, and 449 patients aged 18 - 65 years with stable plaque psoriasis were enrolled from 25 hospitals (such as the First Affiliated Hospital of China Medical University). Eligible patients had a baseline physician's global assessment (PGA) score of ≥ 3 points, baseline body surface area (BSA) involvement of 5% - 30%, and a target lesion psoriasis area and severity index (TL-PASI) for plaque elevation of ≥ 3 points. Participants were randomly assigned in a 2:2:1 ratio to the test group ( n = 179), reference group ( n = 180), and placebo group ( n = 90), and applied the domestic calcipotriol/betamethasone dipropionate ointment, originator product, and ointment base respectively, once daily in the evening for 4 weeks. Efficacy and safety were assessed at weeks 1, 2, and 4. The primary efficacy endpoints were the treatment success rates and clinical success rates in each group at week 4. The per-protocol set (PPS) was used for the primary efficacy analysis, and the intention-to-treat (ITT) set for supplementary efficacy analysis. Equivalence between the test and reference preparations was tested using the Cochran-Mantel-Haenszel method adjusted for randomization strata. Superiority of the test and reference preparations over the placebo was also tested. Measurement data were compared among the 3 groups using analysis of variance or non-parametric tests, while treatment success rates, clinical success rates, and incidence rates of adverse reactions were compared using the chi-square test. Results:The ITT, PPS, and safety sets included 447, 420, and 448 patients, respectively. In the ITT set, patients were aged 43.6 ± 12.8 years, including 320 (71.6%) males and 127 (28.4%) females, and the disease duration was 11.21 ± 9.05 years; 316 (70.7%) had a PGA score of 3 points and 131 (29.3%) had a PGA score of 4 - 5 points. No significant differences in the baseline characteristics (including age, sex, disease duration and disease severity) were observed among the 3 groups (all P > 0.05). Based on the PPS analysis, the treatment success rates were 57.9% (99/171) in the test group, 50.3% (86/171) in the reference group, and 7.7% (6/78) in the placebo group, and the clinical success rates were 57.9% (99/171), 50.3% (86/171), and 10.3% (8/78), respectively; both the test and reference groups were superior to the placebo group in both treatment and clinical success rates (all P < 0.001) ; the rate differences for treatment success (90% confidence interval [ CI]: -1.3% - 16.4%) and clinical success (90% CI: -1.3% - 16.3%) between the test and reference groups were entirely within the pre-defined equivalence margin (-20% - 20%). Subgroup analyses by baseline PGA scores: for patients with a baseline PGA score of 3 points, the treatment success rates in the test, reference, and placebo groups were 60.8% (73/120), 52.1% (62/119), and 11.1% (6/54), respectively, and the corresponding clinical success rates were 61.7% (74/120), 53.8% (64/119), and 13% (7/54), respectively; the test and reference groups did not differ significantly in treatment or clinical success rates (both P > 0.05), but both showed higher success rates than the placebo group (all P < 0.001) ; the results of statistical comparisons among the 3 groups in patients with a baseline PGA score of 4 - 5 points were consistent with those observed in patients with a baseline PGA score of 3 points. The percentage reductions in PGA and TL-PASI scores from baseline to weeks 1, 2, and 4 showed significant differences among the 3 groups, which were significantly higher in the test and reference groups than in the placebo group (all P < 0.001), but did not differ between the test and reference groups (all P > 0.05). The primary adverse reactions were local skin reactions, such as pruritus, pain, and erythema. The incidence rates of adverse reactions were 8.9% (16/179) in the test group, 7.3% (13/179) in the reference group, and 7.8% (7/90) in the placebo group, with no significant difference among the 3 groups ( P > 0.05) . Conclusions:The domestic calcipotriol/betamethasone dipropionate ointment demonstrated clinical equivalence to the originator product in the treatment of stable plaque psoriasis, and the two agents exhibited comparable efficacy for patients with varying degrees of disease severity, and were comparable in the speed and degree of clinical improvement, with similar favorable safety profiles.

Background::Hepatitis B poses a heavy burden for children in China, however, the national studies on the distributional characteristics and health care costs of children with severe hepatitis B is still lacking. This study aimed to analyze the disease characteristics, health economic effects, and medical cost for children with severe hepatitis B in China.Methods::Based on patient information in the Hospital Quality Monitoring System, cases with severe hepatitis B were divided into four groups according to age, and the etiology and symptoms of each group were quantified. The cost of hospitalization was calculated for cases with different disease processes, and severity of disease. The spatial aggregation of cases and the relationship with health economic factors were analyzed by Moran’s I analysis. Results::The total number of children discharged with hepatitis B from January 2016 to April 2022 was 1603, with an average age of 10.5 years. Liver failure cases accounted for 43.48% (697/1603) of total cases and cirrhosis cases accounted for 11.23% (180/1603). According to the grouping of disease progression, there were 1292 cases without associated complications, and the median hospitalization cost was $818.12. According to the spatial analysis, the aggregation of cases was statistically significant at the prefectural and provincial levels in 2019, 2020, and 2021 (all P <0.05). The number of severe cases was negatively correlated with gross domestic product (Moran’s I <0) and percentage of urban population (Moran’s I <0), and positively correlated with the number of pediatric beds per million population (Moran’s I >0). Conclusion::The number of severe hepatitis B cases is low in areas with high gross domestic product levels and high urban population ratios, and health care costs have been declining over the years.

Traditional Chinese medicine (TCM) is a well-accepted therapy for atopic dermatitis (AD). However, there are currently no evidence-based guidelines integrating TCM and Western medicine for the treatment of AD, limiting the clinical application of such combined approaches. Therefore, the China Association of Chinese Medicine initiated the development of the current guideline, focusing on key issues related to the use of TCM in the treatment of AD. This guideline was developed in accordance with the principles of the guideline formulation manual published by the World Health Organization. A comprehensive review of the literature on the combined use of TCM and Western medicine to treat AD was conducted. The findings were extensively discussed by experts in dermatology and pharmacy with expertise in both TCM and Western medicine. This guideline comprises 23 recommendations across seven major areas, including TCM syndrome differentiation and classification of AD, principles and application scenarios of TCM combined with Western medicine for treating AD, outcome indicators for evaluating clinical efficacy of AD treatment, integration of TCM pattern classification and Western medicine across disease stages, daily management of AD, the use of internal TCM therapies and proprietary Chinese medicines, and TCM external treatments. Please cite this article as: Du XR, Wu MY, Tao MC, Lin Y, Gu CY, Wu MF, Cao Y, Chen DC, Li W, Wang HW, Wang Y, Wang Y, Lu HZ, Liu X, Su XF, Li FL. Clinical practice guidelines for the diagnosis and treatment of atopic dermatitis with integrative traditional Chinese and Western medicine. J Integr Med. 2025; 23(6):641-653.
Dermatitis, Atopic/drug therapy* ; Humans ; Medicine, Chinese Traditional/methods* ; Integrative Medicine ; Drugs, Chinese Herbal/therapeutic use* ; Practice Guidelines as Topic

OBJECTIVE: The study aim was to investigate the effects of exposure to multiple environmental organic pollutants on cardiopulmonary health with a focus on the potential mediating role of oxidative stress. METHODS: A repeated-measures randomized crossover study involving healthy college students in Beijing was conducted. Biological samples, including morning urine and venous blood, were collected to measure concentrations of 29 typical organic pollutants, including hydroxy polycyclic aromatic hydrocarbons (OH-PAHs), bisphenol A and its substitutes, phthalates and their metabolites, parabens, and five biomarkers of oxidative stress. Health assessments included blood pressure measurements and lung function indicators. RESULTS: Urinary concentrations of 2-hydroxyphenanthrene (2-OH-PHE) ( β = 4.35% [95% confidence interval ( CI): 0.85%, 7.97%]), 3-hydroxyphenanthrene ( β = 3.44% [95% CI: 0.19%, 6.79%]), and 4-hydroxyphenanthrene (4-OH-PHE) ( β = 5.78% [95% CI: 1.27%, 10.5%]) were significantly and positively associated with systolic blood pressure. Exposures to 1-hydroxypyrene (1-OH-PYR) ( β = 3.05% [95% CI: -4.66%, -1.41%]), 2-OH-PHE ( β = 2.68% [95% CI: -4%, -1.34%]), and 4-OH-PHE ( β = 3% [95% CI: -4.68%, -1.29%]) were negatively associated with the ratio of forced expiratory volume in the first second to forced vital capacity. These findings highlight the adverse effects of exposure to multiple pollutants on cardiopulmonary health. Biomarkers of oxidative stress, including 8-hydroxy-2'-deoxyguanosine and extracellular superoxide dismutase, mediated the effects of multiple OH-PAHs on blood pressure and lung function. CONCLUSION Exposure to multiple organic pollutants can adversely affect cardiopulmonary health. Oxidative stress is a key mediator of the effects of OH-PAHs on blood pressure and lung function.
Humans ; Oxidative Stress/drug effects* ; Male ; Cross-Over Studies ; Female ; Young Adult ; Environmental Pollutants/toxicity* ; Environmental Exposure/adverse effects* ; Biomarkers/blood* ; Adult ; Blood Pressure/drug effects* ; Polycyclic Aromatic Hydrocarbons/urine* ; Beijing

AIM To investigate the effects of Shuyu Pills combined with evolimus on the epithelial mesenchymal transformation of triple negative breast cancer cells 4T1 and MDA-MB-231 induced by TGF-β1.METHODS The 4T1 and MDA-MB-231 cells were divided into the blank group and the induction group to induce the epithelial mesenchymal transformation with TGF-β1 cytokine treatment,followed by the assignment into the model group,the Shuyu Pills group,the everolimus group and the Shuyu Pills combined with everolimus group.CCK8 method,plate cloning method,cell scratch test and Transewll test were used to detect the proliferation,cloning formation,migration and invasion ability of the cells whose expressions of E-cadherin,N-cadherin,Vimentin,MMP9,MMP2 and pathway proteins PTEN,PI3K,Akt and mTOR were detected by Western blot.RESULTS Compared with the blank group,the induction group displayed a cell morphological change from epithelioid to stromal,decreased expression of E-cadherin protein(P＜0.01);and increased protein expressions of N-cadherin and Vimentin(P＜0.05).Compared with the model group,each group intervened with the medicine displayed decreased proliferation,clone formation,migration and invasion ability of both kinds of cells(P＜0.01);increased protein expressions of PTEN and E-cadherin(P＜0.05,P＜0.01);and decreased protein expressions of PI3K,Akt,mTOR,N-cadherin,Vimentin,MMP9 and MMP2(P＜0.05,P＜0.01);and more significantly in the Shuyu Pills combined with evolimus group(P＜0.05,P＜0.01).CONCLUSION With a more ideal effect than the single uses in inhibiting the TGF-β1-induced epithelial mesenchymal transformation of triple-negative breast cancer cells,the combination use of Shuyu Pills and everolimus may work through the regulation of PI3K/Akt/mTOR signaling pathway.

Spine fracture and dislocation are common traumatic spinal conditions that often require surgical intervention due to compromised spinal stability. Surgical approaches include anterior, posterior, and combined anterior-posterior spinal procedures. According to the specific surgical requirements, patients may be placed in the prone position or repositioned between prone and supine positions during surgery. Intraoperative repositioning has become an essential step in patient positioning. However, during repositioning, patients with spinal fracture and dislocation are at increased risk for complications such as hemodynamic instability, nerve injury, and pressure injuries to the skin and soft tissue. Notably, due to the instability of the spinal cord, even minor manipulations can further exacerbate the damage, potentially leading to severe outcomes like paraplegia. Although the current clinical guidelines provide instructive recommendations for standard position, there remains no specific protocols for intraoperative repositioning in patients with spine fracture and dislocation. With a concern for the lack of clinical studies on positioning techniques, risk prevention, and operational norms for special patients, no applicable guidelines or standards are available. A consensus was required to provide clinical reference, meet the requirements of surgical treatment, and minimize the safety risks of patients caused by improper placement of positions. Professional Committee of Operating Room Nursing of Shaanxi Nursing Association organized experts in nursing management and operating room nursing from major hospitals across China to formulate Expert consensus on intraoperative repositioning for patients with spinal fracture and dislocation ( version 2025). The consensus provides 11 recommendations covering pre-repositioning preparation, intraoperative maneuvers, and post-repositioning observation, aiming to provide references for clinical standardization of the intraoperative repositioning process and protection of patients′ safety.