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 explore Lijin Zhenggu Therapy combined with heat supplementing needles on cartilage damage, immune balance, and liver X receptor NF-κB in knee osteoarthritis of New Zealand white rabbits.Methods:Totally　60 New Zealand white rabbits were divided into normal group, model group, Lijin Zhenggu Therapy group, heat supplementing needles group, and a combination group using random number table method, with 12 rabbits in each group. Except for the normal group, all other groups were established with knee osteoarthritis models. The Lijin Zhenggu Therapy group was treated with Lijin Zhenggu Therapy, the heat supplementing needles group was treated with heat supplementing needles, the combination group was treated with Lijin Zhenggu Therapy combined with heat supplementing needles. The pain threshold of each group of white rabbits was observed using a pain meter; HE staining was used to observe the morphology of cartilage damage in each group of white rabbits; ELISA was used to detect PGE 2, IL-1β and β-EP in the articular cartilage tissue of white rabbits in each group; PCR was used to detect the levels of LXRα and NF-κB mRNA. Western blot was used to detect toll like receptor 4 (TLR4), myeloid differentiation factor (MyD88), interferon regulatory factor-7 (IRF-7) in synovial tissue of rabbits in each group. Results:Compared with model group, the pain threshold of rabbits in heat supplementing needles group, Lijin Zhenggu Therapy group and combination group increased ( P<0.05); the levels of PGE 2 and IL-1β decreased ( P<0.05), while the level of β-EP increased ( P<0.05). LXRα mRNA level increased ( P<0.05), and NF-κB mRNA level decreased ( P<0.05); the expressions of TLR4, MyD88, IRF-7 and NF-κB P65 in synovial tissue decreased ( P<0.05). Conclusions:Lijin Zhenggu Therapy combined with heat supplementing needles can reduce the levels of PGE 2 and IL-1β, increase β-EP level, improve pain and cartilage tissue morphology. The mechanism may be related to the regulation of liver X receptor nuclear factor NF-κB pathway, reduction of inflammatory reactions and immunity maintaining.

Objective To investigate the activated phenotype and the expression of the receptor of advanced glycation endproducts(RAGE)of astrocytes after hypoxic-ischemic brain damage(HIBD)in neonatal rats and the effects of gastrodin(GAS)intervention on them.Methods Totally 48 neonatal 3 days SD rats were used to construct HIBD model and randomly divided into sham group,HIBD group and HIBD+GAS group(100 mg/kg),and the expressions of Al type astrocyte marker C3,A2 type astrocyte marker S100A10,RAGE,tumor necrosis factor-α(TNF-α),brain-derived neurotrophic factor(BDNF),and insulin-like growth factor(IGF-1)in the corpus callosum of the ischemic side were detected by Western blotting and immunohistochemical staining on day 1 and day 3 after HIBD.TNC-1 cells were divided into control group,oxygen glucose deprivation(OGD)group,OGD+GAS(0.34 mmol/L)group and GAS group,and then the protein expressions of RAGE,TNF-α,BDNF and IGF-1 were detected by Western blotting and immunofluorescence.Results In vivo,Western blotting showed that compared with the sham group,the protein expression levels of C3,S100A10,RAGE,TNF-α and IGF-1 in the 1 day and 3 days groups after HIBD group in 1 day group were significantly higher than those in the sham group(P＜0.05),but the protein expression level of BDNF decreased in 1 day group and increased in 3 days group(P＜0.05).Compared with the HIBD group,the C3,RAGE and TNF-α protein expression levels were significantly attenuated in the HIBD+GAS group(P＜0.05),and the protein expression levels of BDNF and IGF-1 further increased(P＜0.05).The protein expression of S100A10 in the 3 days group was higher than that in the HIBD group after GAS treatment(P＜0.05).The immunohistochemical staining results of C3,S100A10,and RAGE in the 1 day and 3 days groups after HIBD were consistent with Western blotting results.Furthermore,the protein expressions of RAGE and TNF-α were significantly enhanced in OGD-stimulated astrocytes(P＜0.05).After GAS intervention,while the expressions of both RAGE and TNF-α decreased significantly(P＜0.05),the expressions of BDNF and IGF-1 increased significantly(P＜0.05).Conclusion With inhibiting the up-regulation of RAGE signal in astrocyte after HIBD and expressions of A1 astrocyte and neuroinflammatory factors,gastrodin can promot the expressions of A2 astrocyte and nutritional factors,which play an important role in neuro-protective effect.

Objective:To evaluate the role of ERBB2 interacting protein (Erbin)in liver tissues in blood coagulation of septic mice.Methods:Thirty SPF healthy male C57BL/6 mice and 30 Erbin knockout mice, aged 8-10 weeks, weighing 20-30 g, were divided into wild-type+ sham operation group (WT+ Sham group), wild-type+ sepsis group (WT+ SEP group), Erbin gene knockout+ sham operation group (EKO+ Sham group) and Erbin gene knockout+ sepsis group (EKO+ SEP group) by a random number table method, with 15 animals in each group. The mouse sepsis model was prepared by the cecal ligation and perforation method in anesthetized animals. Eye blood samples were collected at 24 h after surgery and liver tissues were obtained for microscopic examination of histopathological changes (by HE staining) which were scored and for determination of plasma alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities (by colorimetry), expression of Erbin and tissue factor (TF) (by Western blot), expression of tissue plasminogen activator (t-PA) and fibrinogen (Fib)mRNA (by quantitative polymerase chain reaction), concentrations of PT, APTT, thrombin time (TT) and Fib (by automatic coagulation analyzer), and plasma TF and interleukin-6 (IL-6) concentrations (by enzyme-linked immunosorbent assay).Results:Compared with WT+ Sham group, the lung injury score was significantly increased, the expression of TF, t-PA mRNA and FGA mRNA was up-regulated, PT, APTT and TT were prolonged, the plasma Fib concentration was increased, and the activities of ALT and AST and concentrations of TF and IL-6 in plasma were increased in WT+ SEP group ( P<0.05). Compared with WT+ SEP group, the lung injury score was significantly increased, the expression of TF, t-PA mRNA and FGA mRNA was up-regulated, PT, APTT and TT were prolonged, the plasma Fib concentration was increased, and the activities of ALT and AST and concentrations of TF and IL-6 in plasma were increased in EKO+ SEP group ( P<0.05). Conclusions:Erbin in liver tissues exerts an endogenous protective effect on blood coagulation by inhibiting the up-regulation of TF expression in septic mice.

OBJECTIVE:Some studies have shown that kinesio taping has positive effects in elevating muscle strength,improving joint stability and reducing pain and oedema in patients after anterior cruciate ligament reconstruction.However,existing studies have divergent results on the clinical efficacy of kinesio taping.In this study,a meta-analysis was conducted to systematically evaluate the effect of kinesio taping in postoperative rehabilitation period following anterior cruciate ligament reconstruction. METHODS:Randomized controlled trials about the effects of kinesio taping on anterior cruciate ligament reconstruction were electronically searched in PubMed,Web of Science,Embase,The Cochrane Library,EBSCO,CNKI,WanFang,and VIP databases,from database inception to December 06,2022.The outcome measures included six continuous variables:quadriceps strength,hamstring strength,knee swelling,knee range of motion,Lysholm knee function score,and Visual Analogue Scale score.EndNote X9.1 was used to screen the literature.The Cochrane Risk Bias Assessment Tool and Jadad Scale were used to evaluate the quality of the included literature.RevMan 5.3 software was used for Meta-analysis. RESULTS:A total of 6 randomized controlled trials involving 252 patients undergoing anterior cruciate ligament reconstruction were finally included.There were 126 cases in control group and 126 in kinesio taping group.The results of Meta-analysis showed that compared with the control group,kinesio taping significantly improved hamstring strength[standardized mean difference(SMD)=0.68,95%confidence interval(CI):0.12 to 1.23,P=0.02)and reduced Visual Analogue Scale score[mean difference(MD)=-0.56,95%CI:-1.04 to-0.08,P=0.02).However,for quadriceps strength,knee swelling,knee range of motion,and Lysholm knee function score,kinesio taping did not show significant difference from the control group(P＞0.05). CONCLUSION:Kinesio taping may help to improve hamstring strength and reduce pain in patients after anterior cruciate ligament reconstruction.However,it cannot significantly improve quadriceps strength,knee swelling,knee range of motion,and functional scores.

Objective:To investigate the clinical value of abdominal adipose volume in predicting early tumor recurrence after resection of hepatocellular carcinoma (HCC).Methods:The retrospective case-control study was conducted. The clinicopathological data of 132 HCC patients with tumor diameter ≤5 cm who were admitted to The First Affiliated Hospital of Army Medical University from December 2017 to October 2019 were collected. There were 110 males and 22 females, aged (51±4)years. All patients underwent resection of HCC. Preoperative computer tomography scanning was performed and the visceral and subcutaneous fats of patients were quantified using the Mimics Research 21.0 software. Based on time to postoperative tumor recurrence patients were divided to two categories: early recurrence and non-early recurrence. Observation indicators: (1) consistency analy-sis; (2) analysis of factors influencing early tumor recurrence after resection of HCC and construction of prediction model. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the t test. Measurement data with skewed distribu-tion were represented as M( Q1,Q3) or M(range), and comparison between groups was conducted using the Mann-Whitney U test. Count data were expressed as absolute numbers, and comparison between groups was conducted using the chi-square test or Fisher exact probability. Consistency analysis was conducted using the intragroup correlation coefficient (ICC) test. Multivariate analysis was performed using the binary Logistic regression model forward method. Independent risk factors influencing early tumor recurrence after resection of HCC were screened. The area under curve (AUC) of receiver operating characteristic (ROC) curve was applied to select the optimal cut-off value to classify high and low risks of recurrence. The Kaplan-Meier method was used to draw survival curve and calculate survival time. The Log-Rank test was used for survival analysis. Results:(1) Consistency analysis. The consistency ICC of abdominal fat parameters of visceral fat volume (VFV), subcutaneous fat volume, visceral fat area, and subcutaneous fat area measured by 2 radiologists were 0.84, 1.00, 0.86, and 0.94, respectively. (2) Analysis of factors influencing early tumor recurr-ence after resection of HCC and construction of prediction model. All 132 patients were followed up after surgery for 662(range, 292-1 111)days. During the follow-up, there were 52 patients with non-early recurrence and 80 patients with early recurrence. Results of multivariate analysis showed that VFV was an independent factor influencing early tumor recurrence after resection of HCC ( odds ratio=4.07, 95% confidence interval as 2.27-7.27, P<0.05). The AUC of ROC curve based on VFV was 0.78 (95% confidence interval as 0.70-0.85), and the sensitivity and specificity were 72.2 % and 77.4 %, respectively. The optimal cut-off value of VFV was 1.255 dm 3, and all 132 patients were divided into the high-risk early postoperative recurrence group of 69 cases with VFV >1.255 dm 3, and the low-risk early postoperative recurrence group of 63 cases with VFV ≤1.255 dm 3. The disease-free survival time of the high-risk early postoperative recurrence group and the low-risk early post-operative recurrence group were 414(193,702)days and 1 047(620,1 219)days, showing a significant difference between them ( χ2=31.17, P<0.05). Conclusions:VFV is an independent factor influen-cing early tumor recurrence of HCC after resection. As a quantitative indicator of abdominal fat, it can predict the prognosis of HCC patients.