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.

Objective To evaluate cardiac involvement in patients with anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV) using echocardiography combined with electrocardiography. Methods A retrospective analysis was performed on the detailed medical records of AAV patients treated in Jining First People’s Hospital between January 2020 and December 2024. Eighty patients were enrolled in the AAV group, and the risk of heart disease was compared between the AAV group and a control group with 80 subjects matched for age, sex, and cardiovascular disease risk factors. Results Electrocardiographic abnormalities were observed in 78.75% of patients in the AAV group, while significant electrocardiographic abnormalities only occurred in symptomatic patients in the control group. There were no differences in left atrial enlargement or interventricular septal thickening between the AAV group and the control group. The overall left ventricular systolic function in the AAV group was lower than that in the control group (8.75% vs. 0). The incidence of reduced diastolic function in the AAV group was significantly higher than that in the control group (37.5% vs. 15%). The incidence rates of tricuspid regurgitation, mitral regurgitation, aortic regurgitation, and pericardial effusion in the AAV group were significantly higher than those in the control group. Pericardial thickening, aortic stenosis, pulmonary hypertension, and rare periaortic granulomas were found in the AAV group, but not in the control group. Conclusion Echocardiography and electrocardiography are important examination methods for evaluating cardiac involvement in AAV. These methods have key roles in disease screening, diagnosis and treatment, follow-up, and prognosis judgment.

BACKGROUND: Doxorubicin hydrochloride (DOX) is extensively used in the treatment of various tumors. However, its clinical application is limited due to dose-dependent cardiotoxicity. Currently, few effective strategies exist to mitigate or eliminate DOX-induced cardiomyopathy (DIC). Although ferroptosis is implicated in DIC and its inhibition partially alleviates the condition, the direct targets of DOX in the progression of cardiotoxicity remain unclear. This study aimed to discover the direct targets of DOX in ferroptosis-mediated DIC. METHODS: A DOX pulldown assay was performed to identify proteins specifically binding to DOX in murine hearts, followed by liquid chromatography-tandem mass spectrometry (LC-MS/MS) to identify candidate proteins. A cardiac injury mouse model was established by DOX treatment. Based on this, multiple ferroptosis biomarkers were detected by flow cytometry, quantitative real-time polymerase chain reaction, western blotting, immunochemistry, etc. Besides, specific activator and inhibitor of signaling pathways were applied to illuminate molecular mechanisms. RESULTS: Glutathione S-transferase P1 (GSTP1) was identified as a DOX target. GSTP1 activity was inhibited in DOX-treated cardiomyocytes, while its overexpression significantly alleviated DIC. Moreover, GSTP1 overexpression inhibited acyl-CoA synthetase long-chain family member 4 (ACSL4)-dependent ferroptosis. Mechanistically, GSTP1 overexpression suppressed c-Jun N-terminal kinase (JNK) phosphorylation, thereby reducing reactive oxygen species (ROS) production and inhibiting ferroptosis in DIC. CONCLUSIONS This study identifies the DOX/GSTP1/JNK axis as a critical pathway mediating ACSL4-dependent ferroptosis in DIC. GSTP1 is highlighted as a potential key mediator of ferroptosis and a promising therapeutic target for DIC.

ObjectiveThrough qualitatively and quantitatively analysis of the differences in chemical composition between the combined decoction and single decoction of Huaganjian and comparison of their core efficacy， to explore the rationality of the flexible clinical application of Huaganjian compound preparations and single-flavored dispensing granules. MethodsUltra performance liquid chromatography-quadrupole-electrostatic field orbitrap high resolution mass spectrometry（UPLC-Q-Exactive Orbitrap MS） was used to qualitatively analyze the combined decoction and single decoction samples of Huaganjian， and meanwhile， the contents of four index components（geniposide， paeoniflorin， hesperidin and paeonol） were quantitatively analyzed by high performance liquid chromatography（HPLC）. Nonalcoholic fatty liver disease（NAFLD） rat model induced by high-fat diet was applied to compare the efficacy of combined decoction and single decoction of Huaganjian. A total of 30 male SD rats were randomly divided into the control group， model group， lovastatin group（1.8 mg·kg^-1）， combined decoction group（1.26 g·kg^-1） and single decoction group（1.18 g·kg^-1）. After successful modeling， lovastatin group， combined decoction group and single decoction group were given corresponding doses of drugs by intragastric administration every day， and the control group and model group were given equal amounts of normal saline by intragastric administration， after 4 weeks of administration， the serum and liver tissues were collected， and the contents of alanine aminotransferase（ALT）， aspartate aminotransferase（AST）， total cholesterol（TC）， triglyceride（TG）， low-density lipoprotein cholesterol（LDL-C） and high-density lipoprotein cholesterol（HDL-C） in serum of rats were detected， and the liver pathological examination was carried out by hematoxylin-eosin（HE） staining and oil red O staining， so as to compare differences of their efficacy. ResultsSeventy chemical components were initially identified and attributed from the lyophilized powder of the combined decoction and single decoction samples of Huaganjian， and there was no obvious difference in composition between the two. Further quantitative analysis showed that the contents of geniposide， paeoniflorin， hesperidin and paeonol in the combined decoction samples were significantly increased when compared with those of the single decoction samples（P<0.01）. The pharmacodynamic results showed that compared with the model group， both the combined and single decoction groups of Huaganjian could improve the liver index of NAFLD rats， reduce the serum levels of AST， ALT， TC， TG and LDL-C， increase the serum level of HDL-C， and ameliorate the pathological changes of liver cell steatosis and fat accumulation. However， there was no significant difference in pharmacodynamic effects between the combined decoction group and the single decoction group. ConclusionThere is no significant difference between the combined decoction and single decoction of Huaganjian in terms of chemical composition， but the contents of the four index components show significantly difference. Both of them can significantly improve the fat accumulation and liver function in NAFLD rats. This study provides a reference basis for the rational clinical application and evaluation of famous classical formula compound preparations and single-flavored dispensing granules.

OBJECTIVE: To retrospectively analyze the clinical data of newly diagnosed acute myeloid leukemia (AML) patients treated with venetoclax combined with azacitidine (Ven/Aza) or standard "3+7" regimen and similar regimens, collect real-world study data, compare the treatment response and adverse events between the two regimens, as well as perform survival analysis. METHODS: To retrospectively analyze the efficacy, survival, and adverse reactions of newly diagnosed AML patients treated with Ven/Aza (24 cases) and "3+7" regimens (117 cases ) in our hospital from September 2009 to March 2023, as well as factors influencing outcomes. A propensity score matching (PSM) was performed on age and Eastern Cooperative Oncology Group performance status (ECOG PS) to obtain a 1:1 matched cohort of 20 pairs, and the efficacy and survival before and after the matching were compared. RESULTS: The median age of patients in the Ven/Aza group was 69 years, while that in the "3+7" group was 56 years (P <0.001). Objective remission rate (ORR) was 62.5% in Ven/Aza group and 74.8% in "3+7" group (P >0.05). The median overall survival (OS) in the Ven/Aza group was 522 days, while that in the "3+7" group was 1 002 days (P >0.05). After controlling the two variables of age and ECOG PS, a PSM cohort of 20 pairs was obtained, in which the ORR was 65% in Ven/Aza group and 60% in "3+7" group (P >0.05). The median OS was 522 days and 629 days, and median progression-free survival (PFS) was 531 days and 198 days between the two groups, respectively. There were no statistically significant differences in OS and PFS between the two groups (both P >0.05). Additionally, the incidence of adverse events in the Ven/Aza group was significantly reduced. CONCLUSION The overall cohort shows that the "3+7" regimen has advantages in efficacy and survival, but Ven/Aza regimen is relatively safer. After performing PSM on age and ECOG PS, the Ven/Aza group showed improved efficacy, and a longer median PFS compared to "3+7" group.
Humans ; Leukemia, Myeloid, Acute/drug therapy* ; Retrospective Studies ; Sulfonamides/administration & dosage* ; Azacitidine/administration & dosage* ; Bridged Bicyclo Compounds, Heterocyclic/administration & dosage* ; Aged ; Middle Aged ; Male ; Female ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Treatment Outcome

OBJECTIVE: To evaluate the efficacy and safety of Shexiang Tongxin Dropping Pill (STDP) in treating stable angina patients with phlegm-heat and blood-stasis syndrome by exercise duration and metabolic equivalents. METHODS: This multicenter, randomized, double-blind, placebo-controlled clinical trial enrolled stable angina patients with phlegm-heat and blood-stasis syndrome from 22 hospitals. They were randomized 1:1 to STDP (35 mg/pill, 6 pills per day) or placebo for 56 days. The primary outcome was the exercise duration and metabolic equivalents (METs) assessed by the standard Bruce exercise treadmill test after 56 days of treatment. The secondary outcomes included the total angina symptom score, Chinese medicine (CM) symptom scores, Seattle Angina Questionnaire (SAQ) scores, changes in ST-T on electrocardiogram and adverse events (AEs). RESULTS: This trial enrolled 309 patients, including 155 and 154 in the STDP and placebo groups, respectively. STDP significantly prolonged exercise duration with an increase of 51.0 s, compared to a decrease of 12.0 s with placebo (change rate: -11.1% vs. 3.2%, P<0.01). The increase in METs was significantly greater in the STDP group than in the placebo group (change: -0.4 vs. 0.0, change rate: -5.0% vs. 0.0%, P<0.01). The improvement of total angina symptom scores (25.0% vs. 0.0%), CM symptom scores (38.7% vs. 11.8%), reduction of nitroglycerin consumption (100.0% vs. 11.3%), and all domains of SAQ, were significantly greater with STDP than placebo (all P<0.01). The changes in Q-T intervals at 28 and 56 days from baseline were similar between the two groups (both P>0.05). Twenty-five participants (16.3%) with STDP and 16 (10.5%) with placebo experienced AEs (P=0.131), with no serious AEs observed. CONCLUSION STDP could improve exercise tolerance in patients with stable angina and phlegm-heat and blood stasis syndrome, with a favorable safety profile. (Registration No. ChiCTR-IPR-15006020).
Humans ; Double-Blind Method ; Drugs, Chinese Herbal/adverse effects* ; Male ; Female ; Middle Aged ; Angina, Stable/physiopathology* ; Aged ; Syndrome ; Treatment Outcome ; Placebos ; Tablets

Mycophenolic acid (MPA), the active moiety of both mycophenolate mofetil (MMF) and enteric-coated mycophenolate sodium (EC-MPS), serves as a primary immunosuppressant for maintaining solid organ transplants. Therapeutic drug monitoring (TDM) enhances treatment outcomes through tailored approaches. This study aimed to develop an evidence-based guideline for MPA TDM, facilitating its rational application in clinical settings. The guideline plan was drawn from the Institute of Medicine and World Health Organization (WHO) guidelines. Using the Delphi method, clinical questions and outcome indicators were generated. Systematic reviews, Grading of Recommendations Assessment, Development, and Evaluation (GRADE) evidence quality evaluations, expert opinions, and patient values guided evidence-based suggestions for the guideline. External reviews further refined the recommendations. The guideline for the TDM of MPA (IPGRP-2020CN099) consists of four sections and 16 recommendations encompassing target populations, monitoring strategies, dosage regimens, and influencing factors. High-risk populations, timing of TDM, area under the curve (AUC) versus trough concentration (C₀), target concentration ranges, monitoring frequency, and analytical methods are addressed. Formulation-specific recommendations, initial dosage regimens, populations with unique considerations, pharmacokinetic-informed dosing, body weight factors, pharmacogenetics, and drug‍-‍drug interactions are covered. The evidence-based guideline offers a comprehensive recommendation for solid organ transplant recipients undergoing MPA therapy, promoting standardization of MPA TDM, and enhancing treatment efficacy and safety.
Mycophenolic Acid/administration & dosage* ; Drug Monitoring/methods* ; Humans ; Organ Transplantation ; Immunosuppressive Agents/administration & dosage* ; Delphi Technique

Debates persist regarding the efficacy and safety of azvudine, particularly its real-world outcomes. This study involved patients aged ≥60 years who were admitted to 25 hospitals in mainland China with confirmed SARS-CoV-2 infection between December 1, 2022, and February 28, 2023. Efficacy outcomes were all-cause mortality during hospitalization, the proportion of patients discharged with recovery, time to nucleic acid-negative conversion (T _NANC), time to symptom improvement (T _SI), and time of hospital stay (T _HS). Safety was also assessed. Among the 5884 participants identified, 1999 received azvudine, and 1999 matched controls were included after exclusion and propensity score matching. Azvudine recipients exhibited lower all-cause mortality compared with controls in the overall population (13.3% vs. 17.1%, RR, 0.78; 95% CI, 0.67-0.90; P = 0.001) and in the severe subgroup (25.7% vs. 33.7%; RR, 0.76; 95% CI, 0.66-0.88; P < 0.001). A higher proportion of patients discharged with recovery, and a shorter T _NANC were associated with azvudine recipients, especially in the severe subgroup. The incidence of adverse events in azvudine recipients was comparable to that in the control group (2.3% vs. 1.7%, P = 0.170). In conclusion, azvudine showed efficacy and safety in older patients hospitalized with COVID-19 during the SARS-CoV-2 omicron wave in China.

Zebrafish larvae are useful for identifying chemicals against lateral line (LL) hair cell (HC) damage and this type of chemical screen mainly focuses on searching for protectors against cell death. To expand the candidate pool of HC protectors, a self-built acoustic escape response (AER)-detecting system was developed to apply both low-frequency near-field sound transmission and AER image acquisition/processing modules. The device quickly confirmed the changed LL HC functions caused by most known ototoxins, protectors, and neural transmission modifiers, or knockdown of LL HC-expressing genes. With ten devices wired in tandem, five 'hit' chemicals were identified from 124 cyclin-dependent kinase inhibitors to partially restore cisplatin-damaged AER in less than a day. AS2863619, ribociclib, and SU9516 among the hits, protected the HCs in the mouse cochlea. Therefore, using free-swimming larval zebrafish, the self-made AER-detecting device can efficiently identify compounds that are protective against HC damage, including cell death and loss-of-function.
Animals ; Zebrafish ; Hair Cells, Auditory/physiology* ; Lateral Line System/cytology* ; Escape Reaction/physiology* ; Larva ; Mice ; Cisplatin/toxicity* ; Drug Evaluation, Preclinical/methods*

Digital technologies have become an integral part of complete denture restoration. With advancement in computer-aided design and computer-aided manufacturing (CAD/CAM), tools such as intraoral scanning, facial scanning, 3D printing, and numerical control machining are reshaping the workflow of complete denture restoration. Unlike conventional methods that rely heavily on clinical experience and manual techniques, digital technologies offer greater precision, predictability, and efficacy. They also streamline the process by reducing the number of patient visits and improving overall comfort. Despite these improvements, the clinical application of digital complete denture restoration still faces challenges that require further standardization. The major issues include appropriate case selection, establishing consistent digital workflows, and evaluating long-term outcomes. To address these challenges and provide clinical guidance for practitioners, this expert consensus outlines the principles, advantages, and limitations of digital complete denture technology. The aim of this review was to offer practical recommendations on indications, clinical procedures and precautions, evaluation metrics, and outcome assessment to support digital restoration of complete denture in clinical practice.
Humans ; Denture, Complete ; Computer-Aided Design ; Denture Design/methods* ; Consensus ; Printing, Three-Dimensional