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.

As people's attention to health continues to increase,the market demand for traditional Chinese medi-cine(TCM)is growing steadily.The quality and safety of Chinese medicinal materials have attracted unprecedent-ed 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 detec-tion 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.Moreo-ver,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.

Background: Hypertension is a major risk factor for cardiovascular diseases, including AF, which is one of the most common cardiac arrhythmias globally. AF is strongly associated with an increased risk of stroke, heart failure (HF), and cardiovascular mortality. Although intensive blood pressure lowering has been shown to reduce adverse cardiovascular events, its effect on the risk of AF remains debated. Some studies suggest a beneficial effect, whereas others are inconclusive. Therefore, a comprehensive review and meta-analysis are needed to clarify these effects. Objective: This study aims to evaluate the impact of intensive blood pressure lowering on the incidence of atrial fibrillation (AF) in hypertensive patients. Methods: We performed a systematic review and meta-analysis by searching PubMed, EMBASE, Scopus, Web of Science, and the Cochrane Library up to September 2, 2024, for randomized controlled trials comparing intensive blood pressure lowering with standard treatment in hypertensive patients. Studies were included if participants were 40 year or older with systolic blood pressure between 130 and 180 mm Hg (1 mm Hg≈0.133 kPa). Data extraction was conducted by 2 independent researchers, and statistical analysis was performed using Review Manager (RevMan) 5.4. Risk ratios (RRs) and 95% confidence intervals (CIs) were calculated. A random-effects model was applied if heterogeneity was detected (I > 50%). Results: A total of 6 randomized controlled trials involving 34,824 participants were included in the analysis. Intensive blood pressure lowering significantly reduced the risk of new-onset AF compared with standard treatment (RR = 0.76, 95% CI = 0.62-0.93, p < 0.01, I = 0%). Reductions were also observed in stroke (RR = 0.71, 95% CI = 0.58-0.87, p < 0.005, I = 7%), HF (RR = 0.67, 95% CI = 0.45-0.99, p = 0.05, I = 53%), and nonfatal coronary events (RR = 0.80, 95% CI = 0.70-0.92, p < 0.005, I = 39%). However, intensive blood pressure lowering had no significant effect on cardiovascular mortality or all-cause mortality compared with standard treatment. Discussion: Intensive blood pressure lowering significantly reduces the risk of AF and other cardiovascular events, such as stroke, HF, and nonfatal coronary events, particularly among high-risk hypertensive patients. These findings support the potential benefits of intensive blood pressure management in reducing AF incidence and improving overall cardiovascular outcomes, but the evidence is limited.

AIM:To investigate the impact of Kir2.1 channels on abnormal spontaneous pacemaker activities induced by hypokalemia and to elucidate the underlying mechanisms.METHODS:Human induced pluripotent stem cell-derived cardiomyocytes(hiPSC-CMs)were transfected with lentiviral particles containing sequences for human Kir2.1,the Kir2.1-E224G mutant,or Kir4.1.Patch clamp techniques were employed to examine the effects of low extracellular potassium concentration([K+]e)of 1 mmol/L on the resting membrane potentials and whole-cell currents of the cells in each group,assessed via both current and voltage clamp modes.RESULTS:Under conditions of 1 mmol/L[K+]e,cur-rent clamp data revealed that hiPSC-CMs overexpressing Kir2.1 channels exhibited both hyperpolarized and depolarized resting membrane potentials,with the depolarized state triggering abnormal pacemaker activities.In contrast,cells overex-pressing the Kir2.1-E224G mutant or Kir4.1 channels displayed only hyperpolarized resting membrane potentials.Voltage clamp analysis indicated that hiPSC-CMs overexpressing Kir2.1 channels produced"N"-shaped whole-cell currents,whereas cells expressing the Kir2.1-E224G mutant or Kir4.1 exhibited typical K+currents.CONCLUSION:Kir2.1 channels play a crucial role in mediating hypokalemia-induced abnormal spontaneous pacemaker activities in human car-diomyocytes through their inward rectification properties.

AIM:This study aims to investigate the protective effect of Buyang-Huanwu decoction(BYHWD)on cerebral ischemia-reperfusion injury(CIRI)in rats,focusing on its role in regulating the autophagy of cerebral micro-vascular endothelial cells(BMECs).METHODS:(1)We established a rat model of middle cerebral artery occlusion/re-perfusion(MCAO/R)and divided the subjects into four groups:sham group,model(MCAO/R)group,BYHWD group,and 3-n-butylphthalide(NBP)group.Neurological deficits were assessed using the Zea Longa score,while the volume of cerebral infarction was measured through 2,3,5-triphenyltetrazolium chloride(TTC)staining.Pathological damage in the ischemic penumbra was evaluated using HE staining,and blood-brain barrier(BBB)permeability was assessed by Evans blue(EB)staining.The ultrastructure of BMECs was analyzed by transmission electron microscopy,and the co-expres-sion and positive cell rate of microtubule-associated protein 1 light chain 3(LC3)in BMECs were determined through im-munofluorescence double staining.Additionally,the protein expression levels of ZO-1,claudin-5 and occludin in the cor-tical region of the ischemic penumbra in rats were examined using Western blot analysis.(2)A rat BMEC model of oxy-gen-glucose deprivation/reoxygenation(OGD/R)was also established.Rat BMECs were categorized into normal control(CON),OGD/R,dimethyl sulfoxide(DMSO),rapamycin and 3-methyladenine groups to observe autophagy levels by monodansylcadaverine(MDC)staining.Furthermore,rat BMECs were divided into CON,OGD/R,BYHWD-containing serum(BHDS)and NBP groups.The cell autophagy was assessed by MDC staining and Western blot,while cell viability was measured by CCK-8 assay.RESULTS:(1)The rats in MCAO/R group exhibited significantly higher neurological scores(P＜0.01)and increased cerebral infarction volumes(P＜0.01)compared with sham group.Severe damage in the ischemic penumbra was observed,characterized by disordered tissue structure,widened intercellular spaces,and compro-mised cellular integrity.The EB dye permeability was notably elevated(P＜0.01),and BMECs showed structural destruc-tion,including damaged cell membranes,swollen Golgi apparatus,dilated endoplasmic reticulum vesicles,and damaged mitochondria.The ratio of LC3+CD31+/CD31+and the protein levels of ZO-1,claudin-5 and occludin were significantly el-evated(P＜0.01).In contrast,the rats in BYHWD and NBP groups demonstrated lower neurological scores(P＜0.01)and reduced cerebral infarction volumes(P＜0.01).Furthermore,EB permeability decreased(P＜0.01),BMEC morphol-ogy improved,and the protein expression levels of ZO-1,claudin-5 and occludin increased(P＜0.05).(2)Rat BMECs in OGD/R group had a significantly elevated autophagy level compared with CON group(P＜0.01),with increased expres-sion of LC3 and beclin-1 proteins and decreased level of P62 protein(P＜0.05).Notably,the cells in BHDS and NBP groups displayed decreased autophagy level compared with OGD/R group,with increased cell viability(P＜0.01),re-duced LC3 and beclin-1 protein expression,and increased P62 protein expression(P＜0.05).CONCLUSION:Buyang-Huanwu decoction alleviates cerebral ischemia-reperfusion injury in rats by inhibiting the autophagy of cerebral microvas-cular endothelial cells.

Aim To investigate the impact of G pro-tein-coupled estrogen receptor 1(GPER1),also known as GPR30 playing a significant role in the nerv-ous system,on neuronal damage and cognitive dysfunc-tion following epileptic seizures.Methods The pro-tein expression levels of GPER1 and the DNA damage marker γ-H2AX in epileptic rats were assessed using Western blot.The hippocampal neuronal damage and apoptosis in pilocarpine-induced epilepsy models were evaluated using Nissl and TUNEL staining techniques,compared with GPER1 knockdown(GPER1-KD)rats with wild-type(WT)controls.The behavioral activi-ties,including memory and spatial learning,were mo-nitored during the chronic phase of epilepsy using the IntelliCage system.Results Compared to the control group,GPER1 protein expression in the cerebral cortex and hippocampus significantly increased 24 hours post-epilepsy onset.In the GPER1-KD+EP group,hipp-ocampal neuronal damage was more severe,with a sig-nificant increase in apoptotic neurons compared to the WT+EP group.The IntelliCage data revealed that during free exploration,nose contact,position learn-ing,and reverse position learning stages in the GPER1-KD+EP group exhibited fewer visits and a higher error rate than in the WT+EP group.Conclu-sions Deficiency in GPER1 impairs memory and spa-tial learning abilities following epilepsy,potentially due to exacerbated neuronal injury,apoptosis,and inflam-mation.GPER1 represents a promising therapeutic tar-get for mitigating post-epileptic nerve damage and cog-nitive impairment.

Aim To construct and analyze the genotype of G protein-coupled receptor kinase 2(GRK2)conditional knockout mice in synoviocytes,and to provide an animal model for stud-ying the function of GRK2 in synoviocytes.Methods Grk2flox/+mice were bred to generate Grk2flox/flox mice,Grk2flox/flox mice were bred to Col1a1-iCre+mice,Grk2flox/+Col1a1-iCre+mice were bred to Grk2flox/flox mice.Grk2flox/flox Col1a1-iCre+mice were ob-tained as target mice.DNA was extracted and amplified by PCR to identify the genotype.Western blot was used to verify the effect of Grk2 knockout in synovium,liver and kidney tissues.HE staining was used to detect the effects of Grk2 conditional knockout in synovial cells on ankle synovium,liver and kidney tissues.Multiple immunofluorescence was used to detect GRK2 expression in synovial cells.Results The results of gene iden-tification showed that Grk2flox/flox Col1a1-iCre+mice had both Flox and Col1a1-iCre genotypes.Western blot results showed that GRK2 expression decreased in synovial tissues of Grk2flox/flox Col1a1-iCre+mice,but there was no significant change in the expression of GRK2 in liver and kidney tissues.HE staining showed that Grk2flox/flox Col1a1-iCre+mice had no significant pathological changes in the ankle synovium,liver and kidney.The results of multiple immunofluorescence showed that GRK2 expression in synovial cells of Grk2flox/flox Col1a1-iCre+mice de-creased.Conclusion Grk2 conditional knockout mice in syno-viocytes are successfully constructed and identified,which pro-vides an animal model for further study of the role of GRK2 in synovial-related diseases.

Objective To investigate the efficacy and influencing factors of programmed death-1(PD-1)inhibitors in neoadjuvant chemotherapy for triple-negative breast cancer(TNBC).Methods A total of 86 patients with TNBC who received neoadjuvant therapy in The Fifth Medical Center,PLA General Hospital between Jan.1,2018,and Jan.1,2024 and met the inclusion criteria were enrolled,and their clinicopathological data were collected.Based on the neoadjuvant treatment regimens,40 patients who received TP+PD-1 inhibitor(paclitaxel+carboplatin+pembrolizumab)were assigned to TP+PD-1 inhibitor group,and 46 patients who received TP(paclitaxel+carboplatin)were assigned to TP group.The efficacy and incidence of adverse events were compared between the 2 groups after 6 cycles of neoadjuvant therapy.According to the efficacy of neoadjuvant therapy,the patients were further categorized into pathological complete response(pCR)group and non-pCR group.Multivariate logistic stepwise regression analysis was performed to identify independent factors influencing neoadjuvant treatment efficacy.Patients were followed up until Dec.31,2024,and survival analysis was conducted using Kaplan-Meier method.Results There was no significant difference in the objective response rates between the TP+PD-1 inhibitor group and TP group after neoadjuvant therapy(95.0%[38/40]vs 91.3%[42/46],P=0.351].However,the pCR rate was significantly higher in the TP+PD-1 inhibitor group compared with the TP group(65.0%[26/40]vs 43.5%[20/46],P=0.047).There were no significant differences between the 2 groups in terms of disease-free survival,overall survival,or incidence of adverse events(all P＞0.05).Multivariate logistic stepwise regression analysis revealed that the expression of Ki-67 and treatment regimen were influencing factors of pCR after neoadjuvant therapy(odds ratio[OR]=3.382,95%confidence interval[95%CI]1.290-8.868,P=0.013;OR=2.524,95%CI 1.013-6.285,P=0.047).One case of distant metastasis and death occurred in the pCR group,while 8 cases of distant metastasis and 4 deaths occurred in the non-pCR group.The disease-free survival was significantly longer in the pCR group than in the non-pCR group(P=0.031),while the overall survival was similar between the 2 groups(P=0.087).Conclusion Compared with the 6-cycle TP regimen,the 6-cycle TP combined with PD-1 inhibitor regimen can improve the pCR rate in the neoadjuvant treatment of TNBC,with manageable adverse events,suggesting it may serve as a preferred option for TNBC neoadjuvant therapy.Ki-67 expression may serve as a predictive biomarker for achieving pCR.TNBC patients who achieved pCR have better disease-free survival than those who did not.

Objective To analyze the risk of bias during the experimental process and the shortcomings of the research report by evaluating the methodological and reporting quality of animal experimental studies on the prevention and treatment of precancerous lesions of gastric cancer(PLGC)using TCM compounds.To provide reference for improving the quality of animal experimental research on the prevention and treatment of PLGC with TCM compounds.Methods Experimental literature about the prevention and treatment of PLGC with TCM compounds was retrieved from CNKI,Wanfang Data,VIP,CBM,PubMed,Cochrane Library,Web of science and Embase from January 1,2014 to February 23,2024.SYRCLE assessment tool and ARRIVE 2.0 guideline were used to score the included literature and calculate the"low-risk"compliance rate for each item.Results Totally 213 articles were finally included,including 189 Chinese articles and 24 English articles.The SYRCLE tool score was(12.86±1.29)points,and the"low risk"compliance rate was 32.79％.The score of the necessary items of the ARRIVE 2.0 guideline was(24.15±2.80)points,and the"low risk"compliance rate was 49.08％;the score of the recommended items was(11.28±3.40)points,and the"low risk"compliance rate was 30.27％.In the SYRCLE tool evaluation,144(67.61％)studies did not elaborate on the method of generating the allocation sequence.All studies did not describe the adequacy of allocation concealment and the blinding method in the implementation of bias.Only 51 studies(23.94％)explicitly proposed the success criteria for PLGC modeling,only 66 studies(30.96％)provided detailed information on the statistical methods used,29 studies(13.62％)provided complete ethical statements,and 22 studies(10.33％)reported conflicts of interest.Conclusion There are many problems in the methodological quality and reporting quality of animal experimental literature on the prevention and treatment of PLGC with TCM compounds published from 2014 to 2024,especially the implementation of the random blinding strategy during the experimental process,the calculation details of the sample size,and the reporting of inclusion and exclusion criteria,etc.There are many deficiencies in this aspect.It is recommended to refer to the SYRCLE evaluation tool and the ARRIVE 2.0 guideline list to design and report the research plan,thereby improving the credibility and standardization of the PLGC animal experimental research results.

Objective: To reveal the molecular biological mechanism of a rare Dc-variant individual using PacBio third-generation sequencing technology. Methods: ABO and Rh blood type identification, DAT, unexpected antibody screening and D antigen enhancement test were conducted by serological testing. The absorption-elution test was used to detect the e antigen. RHCE gene typing was performed by PCR-SSP, and the 1-10 exons of RHCE were sequenced by Sanger sequencing. The full-length sequences of RHCE, RHD and RHAG were detected by PacBio third-generation sequencing technology. Results: Serological findings: Blood type O, Dc-phenotype, DAT negative, unexpected antibody screening negative; enhanced D antigen expression; no detection of e antigen in the absorption-elution test. PCR-SSP genotyping indicated the presence of only the RHCE c allele. Sanger sequencing results: Exons 5-9 of RHCE were deleted, exon 1 had a heterozygous mutation at c. 48G/C, and exon 2 had five heterozygous mutations at c. 150C/T, c. 178C/A, c. 201A/G, c. 203A/G and c. 307C/T. Third-generation sequencing results: RHCE genotype was RHCE 02N. 08/RHCE-D(5-9)-CE; RHD genotype was RHD 01/RHD 01; RHAG genotype was RHAG 01/RHAG 01 (c. 808G>A and c. 861G>A). Conclusion: This Dc-individual carries the allele RHCE 02N. 08 and the novel allele RHCE-D(5-9)-CE. The findings of this study provide data support and a theoretical basis for elucidating the molecular mechanisms underlying RhCE deficiency phenotypes.