As people’s attention to health continues to increase, the market demand for traditional Chinese medicine (TCM) is growing steadily. The quality and safety of Chinese medicinal materials have attracted unprecedented social attention. In particular, the issue of exogenous harmful residue pollution in TCM has become a hot topic of concern for both regulatory authorities and society. The Chinese Pharmacopoeia 2025 Edition further refines the detection methods and limit standards for exogenous harmful residues in TCM. This not only reflects China’s high-level emphasis on the quality and safety of TCM but also demonstrates the continuous progress made by China in the field of TCM safety supervision. Basis on this study, by systematically reviewing the development history of the detection standards for exogenous harmful residues in TCM and analyzing the revisions and updates of these detection standards in the Chinese Pharmacopoeia 2025 Edition, deeply explores the key points of the changes in the monitoring standards for exogenous harmful residues in TCM in the Chinese Pharmacopoeia 2025 Edition. Moreover, it interprets the future development directions of the detection of exogenous residues in TCM, aiming to provide a reference for the formulation of TCM safety supervision policies.

This study aimed to investigate the effects of Zhiwei Fuwei Pills on mitochondrial apoptosis in the rat model of precancerous lesions of gastric cancer(PLGC) based on the microRNA-21(miRNA-21)/B-cell lymphoma-2(Bcl-2) signaling pathway. Eighty-five 5-week-old male SPF-grade SD rats were selected, of which 75 were fed with N-methyl-N'-nitro-N-nitrosoguanidine(MNNG) for multifactorial modeling, and the PLGC model was established after 26 weeks. The rats were randomly grouped as follows: model, folic acid(0.002 g·kg~(-1)), low-dose(0.42 g·kg~(-1)) Zhiwei Fuwei Pills, medium-dose(0.84 g·kg~(-1)) Zhiwei Fuwei Pills, and high-dose(1.67 g·kg~(-1)) Zhiwei Fuwei Pills, with 15 rats in each group. Additionally, 10 rats were assigned to a blank group and administrated with an equivalent volume of normal saline by gavage. After four weeks of continuous drug administration, the gastric mucosal tissue was collected. Hematoxylin-eosin(HE) staining was performed to reveal the pathological changes in the gastric mucosa. Terminal deoxynucleotidyl transferase dUTP nick end labeling(TUNEL) was employed to detect apoptosis in gastric mucosal epithelial cells. RT-PCR was adopted to determine the mRNA levels of miRNA-21, phosphatase and tensin homolog(PTEN), Bcl-2, Bcl-2-associated X protein(Bax), and cysteinyl aspartate-specific protease 3(caspase-3). Western blot was employed to determine the protein levels of PTEN, Bcl-2, Bax, and caspase-3. Immunohistochemistry(IHC) was used to detect the positive expression of PTEN, Bcl-2, and Bax in the gastric mucosal tissue. Transmission electron microscopy(TEM) was employed to observe the morphological and structural changes in mitochondria. The results showed that compared with model group, the drug administration groups showed alleviated pathological changes, with increased apoptotic cells, down-regulated mRNA levels of miRNA-21 and Bcl-2, up-regulated mRNA and protein levels of PTEN, Bax, and caspase-3, and down-regulated protein level of Bcl-2. In addition, the drug administration groups exhibited mitochondrial swelling and rupture and reduction of cristae, which indicated mitochondrial apoptosis. These findings suggest that Zhiwei Fuwei Pills can effectively improve mitochondrial apoptosis in PLGC cells by regulating the miRNA-21/Bcl-2 signaling pathway.
Animals ; MicroRNAs/metabolism* ; Male ; Apoptosis/drug effects* ; Stomach Neoplasms/physiopathology* ; Proto-Oncogene Proteins c-bcl-2/genetics* ; Rats ; Rats, Sprague-Dawley ; Drugs, Chinese Herbal/administration & dosage* ; Mitochondria/genetics* ; Signal Transduction/drug effects* ; Precancerous Conditions/drug therapy* ; Humans ; PTEN Phosphohydrolase/genetics*

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*

Cardiac fibrosis is characterized by an elevated amount of extracellular matrix (ECM) within the heart. However, the persistence of cardiac fibrosis ultimately diminishes contractility and precipitates cardiac dysfunction. Circular RNAs (circRNAs) are emerging as important regulators of cardiac fibrosis. Here, we elucidate the functional role of a specific circular RNA CELF1 in cardiac fibrosis and delineate a novel feedback loop mechanism. Functionally, circ-CELF1 was involved in enhancing fibrosis-related markers' expression and promoting the proliferation of cardiac fibroblasts (CFs), thereby exacerbating cardiac fibrosis. Mechanistically, circ-CELF1 reduced the ubiquitination-degradation rate of BRPF3, leading to an elevation of BRPF3 protein levels. Additionally, BRPF3 acted as a modular scaffold for the recruitment of histone acetyltransferase KAT7 to facilitate the induction of H3K14 acetylation within the promoters of the Celf1 gene. Thus, the transcription of Celf1 was dramatically activated, thereby inhibiting the subsequent response of their downstream target gene Smad7 expression to promote cardiac fibrosis. Moreover, Celf1 further promoted Celf1 pre-mRNA transcription and back-splicing, thereby establishing a feedback loop for circ-CELF1 production. Consequently, a novel feedback loop involving CELF1/circ-CELF1/BRPF3/KAT7 was established, suggesting that circ-CELF1 may serve as a potential novel therapeutic target for cardiac fibrosis.

Objective: To investigate the impact of temperature changes between neighboring days (TCN) on the mortality risk of respiratory diseases, so as to provide the evidence for the study of deaths from respiratory diseases caused by climate change. Methods: The monitoring data of deaths from respiratory diseases in Zibo City from 2015 to 2019 were collected from Shandong Provincial Management Information System for Chronic Diseases and Cause of Death Surveillance. The meteorological and air pollutant data of the same period were collected from China Meteorological Data Website and ChinaHighAirPollutants dataset. The effect of TCN on the risk of deaths from respiratory diseases was examined using a generalized additive model combined with a distributed lag non-linear model, and subgroup analyses for gender and age were conducted. The disease burden attributed to TCN at different intervals was assessed by calculating attributable fraction. Results: Totally 11 767 deaths from respiratory diseases were reported in Zibo City from 2015 to 2019, including 6 648 males (56.50%) and 5 119 females (43.50%). There were 1 307 deaths aged <65 years (11.11%), and 10 460 deaths aged 65 years and older (88.89%). A monotonically increasing exposure-response relationship was observed between TCN and deaths from respiratory diseases in the general population, females, and the population aged 65 years and older. The 95th percentile of TCN (P95, 3.84 ℃) reached the peak at a cumulative lagged of day 11 (RR=2.063, 95%CI: 1.261-3.376). The results of subgroup analyses showed greater impacts on females and the population aged 65 years and older, with cumulative lagged effects peaking at day 12 (RR=3.119, 95%CI: 1.476-6.589) and day 11 (RR=2.107, 95%CI: 1.260-3.523). The results of attributional risk analysis showed that next-day warming might increase the attributable risk of deaths from respiratory diseases, and next-day cooling might decrease the attributable risk. Conclusion Next-day warming may increase the mortality risk of respiratory diseases, and has greater impacts on females and the population aged 65 years and older.

OBJECTIVE To test and compare the median effective dose(ED50) of ciprofol for gastroscope in patients of different genders and ages. METHODS Patients who planed to undergo gastroscope examination and treatment from March 2023 to April 2023 were selected, and divided into four groups according to stratified random method: N1 group(non-elderly male patients), N2 group(non-elderly female patients), N3 group(elderly male patients), and N4 group(elderly female patients). All patients received intravenous injection of 0.1 μg·kg−1 sufentanil followed by injection of the test dose of ciprofol according to Dixon’s modified sequential method. Gastroscope was performed after the disappearance of the eyelash reflex. The initial dose of ciprofol in all four groups was 0.4 mg·kg−1, and the ratio of adjacent doses was 1∶1.1. The next patient would receive a 10% increase in the dose of ciprofol if the patient experienced positive reactions such as coughing, frowning, and body movements during the endoscopy process. Otherwise, it would be judged as a negative reaction, and the next patient would receive a 10% decrease in the dose of ciprofol. The transition from a positive reaction to a negative reaction was defined as a turning point, and the study was terminated when seven turning points occurred. Hemodynamic parameters, oxygen saturation and adverse reactions were recorded at different time points. The Probit regression analysis method was used to calculate the ED50 of ciprofol for four groups. RESULTS The ED50 of ciprofol combined with 0.1 μg·kg−1 sufentanil for gastroscope in the non-elderly men, non-elderly women, elderly men, and elderly women were 0.409, 0.373, 0.356, 0.327 mg·kg−1, respectively. The ED50 of ciprofol in the N1 group was significantly higher compared with the N2 group and N3 group(P<0.05). The ED50 of ciprofol in the N4 group was significantly lower compared with the N2 group and N3 group(P<0.05). CONCLUSION The ED50 of ciprofol is significantly different among gastroscope patients of different genders and ages, which is lower in female patients than in male patients, and is lower in older patients than in non-elderly patients.

Circular RNAs (circRNAs) are a kind of non-coding RNA (ncRNA) with covalent closed-loop structure. They have attracted more and more attention because of their high stability, evolutionary conservatism, and tissue expression specificity. It has shown that circRNAs are involved in the development of a variety of diseases including malignant tumors recently. Nasopharyngeal carcinoma (NPC) is a malignant tumor that occurs in the nasopharynx and has a unique ethnic and geographical distribution in South China and Southeast Asia. Epstein-Barr virus (EBV) infection is closely related to the development of NPC. Radiotherapy and chemotherapy are the mainstays of treatment for NPC. But tumor recurrence or distant metastasis is the leading cause of death in patients with NPC. Several studies have shown that circRNAs, as gene expression regulators, play an important role in NPC and affect the progression of NPC. This review mainly summarized the research status of abnormally expressed circRNAs in NPC and EBV-encoded circRNAs. We also discussed the possibility of circRNAs as a therapeutic target, diagnostic and prognostic marker for NPC.

The development of animal early embryos commences with the reprogramming of terminally differentiated gametes into totipotent zygotes following fertilization. During the initial stages of embryonic development, the transcriptional levels of zygotic genome remain silent and maternal gene products dominate the regulation of development. As embryonic development progresses, the maternal gene products undergo phased degradation while the zygotic genome gradually activates transcription, marking the transition from the maternal regulation to the zygotic genome regulation in early embryonic development, which is also referred to as the maternal-zygotic transition (MZT). Zygotic genome activation (ZGA) is a critical turning process in this transition, and its accurate occurrence is crucial for early embryonic development and cell fate decisions. However, the regulatory factors and molecular mechanisms of ZGA remain poorly understood. Studies have shown that ZGA varies greatly among different species and may be affected by a variety of regulatory factors such as DNA methylation, histone modification, non-coding RNA, chromatin remodeling and ZGA related factors. Here, we review the research progress of the above regulatory factors affecting ZGA, which can provide valuable insights for further investigations into the ZGA related mechanisms of early embryos.

Interventions for endometriosis(EMs)include surgical excision of lesions and hormonal therapy,which usually have limited efficacy and adverse drug reactions.Traditional Chinese medicine(TCM)has the multi-component and multi-target characteristics,which can help patients achieve good clinical benefits by intervening in different parts of the disease.In this paper,we briefly discuss the modern pharmacology of Sanlang and Curcuma longa,and deeply summarize the possible mechanisms of action of TCM monomer and classical compound extracts and their active ingredients through signal pathways in inflammation,immune system,angiogenesis,hormone regulation,etc.,so as to provide theoretical bases for the clinical use of TCM monomers,drug-to-drug groups and compounds in the treatment of EMs.