The prescription of Qidong Yixin oral liquid is derived from the experience of national medical master Ren Jixue in treating viral myocarditis （VMC）. It has the functions of tonifying Qi， nourishing the heart，calming the mind， and relieving palpitations. It is used to treat VMC and angina pectoris of coronary heart disease caused by deficiency of both Qi and Yin. However，the understanding of its efficacy evidence， advantageous aspects， dosage and administration， and medication safety remains insufficient in clinical practice. Therefore，the development of the Expert Consensus on the Clinical Application of Qidong Yixin Oral Liquid （hereinafter referred to as consensus） was initiated. Consensus strictly followed the process and methods of the expert consensus on the clinical application of Chinese patent medicines of the China Association of Chinese Medicine，successively completing multiple tasks such as the consensus project initiation，determination of clinical problems，evidence search and evaluation，formation of recommendation opinions and consensus suggestions，solicitation of opinions，peer review， submission for review and release， and so on. Consensus formed a total of 10 recommendation opinions and 12 consensus suggestions，clarifying the clinical positioning，efficacy advantages，syndrome differentiation，dosage and administration，combination therapy，timing of medication，adverse reactions，contraindications， and precautions of Qidong Yixin oral liquid，indicating that it has good clinical advantages and safety in the treatment of VMC and angina pectoris of coronary heart disease，providing norms and references for physicians to safely and rationally apply Qidong Yixin oral liquid. Consensus was reviewed and approved for release by the Standardization Office of the China Association of Chinese Medicine on December 23， 2024. Standard number：GSCACM-376-2024.

Background/Aims: Liver transplantation (LT) following total hepatectomy is a life-saving treatment for hepatocellular carcinoma (HCC). The HCC recurrence after LT hinders the effectiveness of the procedure. The objective of this study is to develop a pre-operative risk stratification model based on a liquid biopsy. Methods: We conducted a comprehensive multi-omics study of 260 HCC patients from three centers, including clinical data, low-coverage whole-genome sequencing of cell-free DNA (cfDNA) from plasma, as well as whole-exome, single-nucleus RNA, and spatial transcriptomics from matched tumor and non-tumor tissues. Results: We identified cfDNA-derived copy number alteration (CNA) signatures associated with post-transplant recurrence. By integrating cfDNA-derived CNA profiles with single-cell transcriptomic data, we traced recurrence-associated cfDNA to a distinct subpopulation of malignant cells within the primary tumor. These cells were embedded in a pro-metastatic microenvironment of specialized endothelial subtypes and cancer-associated fibroblasts. Notably, most recurrence-associated lesions were detectable in cfDNA prior to liver transplantation (LT). Building on these insights, we developed the ZJU Criteria based on CNA fragments and tumor markers, a pre-LT risk prediction tool that integrates conventional clinical factors with cfDNA-derived CNA signatures, and validated it using internal and independent external cohorts. Conclusion Our findings suggest that post-transplant recurrence commonly originates from advanced subclones that emerge late during tumor evolution. The ZJU Criteria provides an accurate, non-invasive strategy that significantly improves pre-LT risk stratification and clinical decision-making for patients with HCC.

ObjectiveTo investigate the protective effect of liver-targeted fibroblast growth factor 21 （FGF21） overexpression against CCl₄-induced acute liver injury （ALI） and its association with silent information regulator 1/glutathione peroxidase 4 （SIRT1/GPX4） expression and ferroptosis-related markers. MethodsFemale ICR mice （8 weeks old） were randomly divided into Control， CCl₄， adeno-associated virus （AAV）-FGF21， and AAV-FGF21 + CCl₄ groups. Liver-targeted FGF21 overexpression was achieved via tail vein injection of AAV8-FGF21 virus with green fluorescent protein （GFP） labeling. ALI was induced by intraperitoneal injection of CCl₄ （0.3 mL/kg）， with sample collection at 12 hours. Body weight and liver weight were recorded to calculate the liver weight/body weight. Alanine aminotransferase （ALT） and aspartate aminotransferase （AST） levels were measured using a biochemical analyzer. FGF21 expression in liver tissues was detected by immunofluorescence. Hepatic histopathology was evaluated by HE staining. RT-qPCR was performed to assess mRNA expression of ferroptosis and iron metabolism-related genes （ACSL4， PTGS2， HJV， FPN， GPX4）， FGF21， and SIRT1. Protein expression of FGF21， SIRT1， and GPX4 were determined by Western blot. Iron content， malondialdehyde （MDA）， glutathione （GSH）， and superoxide dismutase （SOD） activity in liver homogenate were quantified using assay kits. ResultsCompared with the Control group， the FGF21 mRNA and protein expression elevated in CCl₄ group； serum ALT/AST levels and liver weight/body weigh increased. The HE staining results showed that the liver cell membranes were ruptured. The mRNA levels of ACSL4 and PTGS2， the iron content and MDA levels all increased （P<0.01）. The mRNA levels of SIRT1， GPX4， HJV， and FPN， the GSH level and SOD activity all decreased （P<0.05）， and the protein levels of SIRT1 and GPX4 both decreased （P<0.05）. Compared with the CCl₄ group， the serum levels of ALT and AST in the AAV-FGF21 + CCl4 group were decreased （P<0.01）， and the liver/body ratio of mice decreased （P<0.01）. The results of HE staining showed that the degree of liver injury was alleviated. The mRNA levels of ACSL4 and PTGS2， iron content and MDA level all decreased （P<0.01）， while the mRNA levels of SIRT1， GPX4， HJV， FPN， GSH level and SOD activity all increased （P<0.05）. The protein levels of SIRT1 and GPX4 both increased （P<0.05）. ConclusionFGF21 overexpression is associated with enhanced SIRT1/GPX4 expression and suppression of ferroptosis features， thereby contributing to the alleviation of CCl₄-induced ALI.

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.

AIM To investigate the promotional effects of esculin combined with bone marrow mesenchymal stem cells(BM-MSCs)transplantation on the repair of spinal cord injury(SCI)in rats.METHODS The rats were randomly divided into the sham operation group,the model group,the esculin group for gavage of 20 mg/kg esculin,the BM-MSCs group for tail vein injection of 1 mL of 1×106/mL BM-MSCs,and the combinaiton treatment group.The SCI rat model was established using Allen's method,followed by the 14 days consecutive corresponding drug administration starting from the 2nd day after modeling.On days 3,7 and 14 of drug administration,the rats had their hind limbs motor function evaluated by the BBB scoring;and their footprint experiment conducted on the 14th day after modeling.After 14 days of administration,the rats had their morphological changes of spinal cord tissue observed with HE staining and Nissl staining;their activities of SOD and GSH,and level of MDA in spinal cord tissue detected by kits;their expressions of MAP2,GAP43 and GFAP in spinal cord tissue detected by immunofluorescence;and their expressions of NQO-1,Nrf-2,Bcl-2 and Bax proteins in spinal cord tissue detected by Western blot.RESULTS Compared with the model group,the groups interved with esculin,or BM-MSCs,or the combination treatment showed improvements in hind limb function and spinal cord tissue morphology(P＜0.05);decreased MDA levels(P＜0.05);increased SOD and GSH activities(P＜0.05);increased MAP2 and GAP43 fluorescence intensity(P＜0.05);decreased GFAP fluorescence intensity(P＜0.05);increased NQO-1,Nrf-2 and Bcl-2 protein expressions(P＜0.05);and decreased Bax protein expression(P＜0.05).And the combination treatment group was observed with an even better effects(P＜0.05).CONCLUSION The combination of esculin and BM-MSCs transplantation can effectively improve the spinal cord tissue damage and hind limb function in SCI rats.This effect may be achieved by activating the Nrf-2/NQO-1 signaling pathway to inhibit oxidative stress response,thereby reducing neuronal apoptosis,blocking glial scar formation,and promoting stem cell differentiation to rebuild neurons.

Objective:To evaluate the efficacy of Tongdu Tiaoshen acupuncture combined with low-frequency electrical pulse in the treatment of neurogenic bladder (NB) caused by spinal cord injury (SCI); To explore its effects on urodynamics.Methods:A randomized controlled trial study was conducted. A total of 116 patients with NB caused by SCI in the First Affiliated Hospital of Hunan University of Chinese Medicine from January 2022 to June 2024 were selected as the observation objects and divided into 2 groups with random number table method, with 58 cases in each group. On the basis of conventional bladder function training, the control group was given low-frequency electronic pulse therapy, while the observation group was treated with the Tongdu Tiaoshen method on the basis of the control group. Both groups were treated continuously for 3 months. The urination conditions of the patients were observed before and after the treatment respectively, and the residual urine volume, single urine volume within 24 hours, the number of urine leaks within 24 hours, and the number of urinations within 24 hours were recorded; urodynamic parameters such as bladder volume, urine flow rate, detrusor pressure, bladder compliance, and detrusor contractility were measured using a urodynamic analyzer; the severity of NB symptoms was evaluated using the Chinese version of the Neurogenic Bladder Symptom Scale (NBSS), and the quality of life was evaluated using the Chinese version of the Short Form Health Assessment Scale (SF-Qualiveen). The levels of IL-1β, IL-6 and TNF-α were detected by ELISA. Adverse reactions were recorded during the treatment period and the clinical efficacy was evaluated.Results:The total effective rate was 91.38% (53/58) in the observation group and 75.86% (44/58) in the control group. There was a statistically significant difference between the two groups ( χ2=5.10, P=0.024). After treatment, the residual urine volume, single urine volume within 24 hours, frequency of urine leakage within 24 hours, and frequency of urination within 24 hours in the observation group were lower than those in the control group ( t values were -15.68, 3.75, -3.81, and -7.54 respectively, P<0.01). The bladder capacity, urine flow rate, detrusor pressure, bladder compliance and detrusor contractility were higher than those of the control group ( t values were 11.04, 7.49, 9.76, 5.65 and 4.36 respectively, P<0.01), while the NBSS score and SF-Qualiveen score were lower than those of the control group ( t values were -10.82 and -9.83 respectively, P<0.01). No obvious adverse reactions occurred in either group during the treatment period. Conclusion:Tongdu Tiaoshen acupuncture combined with low-frequency electrical pulses can improve the bladder function of NB caused by SCI, restore urodynamics, and improve the quality of life. Its mechanism may be related to the inhibition of inflammatory responses.

In this study, RAW264.7 cells were employed to investigate the effects of honey-processed Astragalus on their energy metabolism and polarization, and explore the scientific connotation of the enhanced efficacy of honey-processed Astragalus on invigorating spleen-stomach and replenishing Qi. The medicated sera were prepared by intragastric administration of rats with water extracts of crude and honey-processed Astragalus, and the composition changes of medicated sera of crude and honey-processed Astragalus were analyzed by using LC-MS technology. The cell survival rates were detected and the concentrations of medicated sera were screened through CCK-8 assay. The differences of cell phagocytic rates, ATP energy metabolism, and NO secretion between crude and honey-processed Astragalus were evaluated by using neutral red phagocytosis assay, ATP detection kit, and NO detection kit. The effects of crude and honey-processed Astragalus on TNF-α secretion of RAW264.7 cells were detected by employing ELISA kit. The effects of crude and honey-processed Astragalus on polarization of RAW264.7 cells were evaluated by utilizing flow cytometry. The differential metabolites related to glycolysis in cell lysates and culture media were screened by using LC-MS technology. The experiment was approved by the experimental animal ethics committee from Shanxi University of Chinese Medicine (No. AWE202407352). The results showed that the contents of betaine, amino acids, and ononin in the prepared medicated sera of rats treated by intragastric administration with water extracts of honey-processed Astragalus increased compared to those in crude one. The results of CCK-8 experiment showed that there were no cytotoxic effects on RAW264.7 cells in the medicated sera of crude and honey-processd Astragalus at different concentration. The phagocytic index and ATP yield both increased to varying degrees after administration of the medicated sera to cells. The secretion of NO in normal and inflammatory cells increased and decreased respectively, and the effect of honey-processed Astragalus was better than that of crude one. The results of ELISA kit showed that the medicated sera of both crude and honey-processed Astragalus could promote the secretion of TNF-α in a concentration-dependent manner, and the promoting effect of honey-processed Astragalus was stronger than that of crude one. The results of flow cytometry showed that the medicated sera of both crude and honey-processed Astragalus could promote M1-type polarization and inhibit M2-type polarization of RAW264.7 cells, and the effect of honey-processed Astragalus was better than that of crude one. Compared to crude Astragalus, the metabolites related to glycolysis in the cell lysates and culture media of the medicated sera of honey-processed Astragalus were generally on the rise, indicating that the effect on promoting glycolysis of honey-processed Astragalus was better than that of crude one. In summary, honey-processed Astragalus can promote the polarization and energy metabolism of RAW264.7 cells, and participate in positive immune regulation, which is correlated with its enhanced effect of invigorating spleen-stomach and replenishing Qi.

OBJECTIVE To evaluate the quality of evidence in the systematic evaluation/meta-analysis of traditional Chinese medicine （TCM） for diabetes retinopathy （DR） based on the GRADE system. METHODS Chinese and English databases were searched to obtain the relevant studies of systematic evaluation/meta-analysis of traditional Chinese medicine in the treatment of DR. The search time was from the establishment of each database to January 13th， 2024. According to the inclusion and exclusion criteria， literature screening was conducted. After extracting relevant information from the included literature， the GRADE system was used to evaluate the quality level of the evidence body in the included studies， and the evidence of the outcome indicators was integrated and summarized. RESULTS A total of 51 studies were ultimately included， encompassing 135 outcome indexes. Among these， 19 indicators （14.1%） were of high quality， 87 （64.4%） were of medium quality， 26 （19.3%） were of low quality， and 3 （2.2%） were of very low quality. Overall， the evidence quality of the outcome indicators in the included studies was medium to low quality. The integrated results of evidence on the efficacy of outcome indexes showed that compared with conventional Western medicine， calcium dobesilate or placebo， TCM had significant advantages in improving overall efficacy， reducing bleeding spot area， reducing macular foveal thickness， and increasing visual improvement rate. In addition，the combination of TCM and conventional Western medicine or calcium dobesilate was significantly more effective than using conventional Western medicine or calcium dobesilate alone. CONCLUSIONS The overall quality of the evidence in the systematic evaluation/meta-analysis study on the treatment of DR with TCM is medium to low quality. Based on existing research findings， TCM demonstrates good clinical efficacy in the treatment of DR.

OBJECTIVE: To investigate the association between SPAG17 gene variant and Familial severe asthenozoospermia, and to assess its impact on the outcome of intracytoplasmic sperm injection (ICSI). METHODS: Two siblings (Probands 1 and 2) with severe asthenozoospermia from a Chinese family who presented at the Reproductive Medicine Center II of Gansu Maternity and Child Health Care Hospital (Gansu Provincial Central Hospital) in May 2023 were selected as study subjects. Clinical data were collected, and sperm morphology and ultrastructure (assessed by transmission electron microscopy) were analyzed. Pathogenic variants were screened using whole exome sequencing (WES) and verified by Sanger sequencing. This study was approved by the Medical Ethics Committee of Gansu Maternity and Child Health Care Hospital (Ethics No.: 2023GSFYLS78). RESULTS: Probands 1 and 2 had primary infertility for 10 and 3 years, respectively, and both exhibited normal semen concentration, but the percentage of progressive motile sperm (PR) was significantly lower than the normal reference value (> 32.00%), measuring 2.33% ± 0.58% and 0.80% ± 0.45%, respectively. Additionally, the percentage of sperms with normal morphology was slightly below the reference range (> 4.00%), with the values of 3.36% ± 0.35% and 2.93% ± 1.36%. Both probands were found to harbor homozygous c.2188C>T (p.Q730*) nonsense variant of the SPAG17 gene (NM_206996.4), for which their mother was a heterozygous carrier (their father had already deceased). Both sibs underwent ICSI treatment using a long gonadotropin-releasing hormone agonist protocol during the follicular phase combined with assisted oocyte activation (AOA). The wife of Proband 1 ultimately gave birth to a healthy girl, whilst the wife of Proband 2 delivered two healthy girls. CONCLUSION The homozygous c.2188C>T (p.Q730*) nonsense variant of the SPAG17 gene is closely related with the severe asthenozoospermia phenotype. Live births can be achieved through ICSI combined with AOA technology, though the overall utilizable embryo rate may be relatively low.
Humans ; Male ; Asthenozoospermia/genetics* ; Adult ; Sperm Injections, Intracytoplasmic ; Pedigree ; Spermatozoa ; Female ; Exome Sequencing

Objective:To compare minimally invasive surgery with traditional open surgery, analyze the current application status of health economic evaluations in the treatment of digestive tract cancers, such as esophageal cancer, gastric cancer, and colorectal cancer by minimally invasive surgery and provide evidence for the rational selection of clinical treatment, alleviation of disease-related economic burdens, and rational allocation of healthcare resources.Methods:By using five databases, i.e. China National Knowledge Infrastructure, Wanfang data, Chinese Biomedical Literature Database, PubMed, and Embase, a database was established to retrieve all the papers about health economic studies of minimally invasive surgery for esophageal cancer, gastric cancer, and colorectal cancer published until December 31, 2023. Literature was analyzed by using software NoteExpress 3.8, and data were processed using Excel 2021. The quality of included papers was evaluated using the CHEERS 2022 checklist, and Meta-analysis was conducted by using software Stata 17.0.Results:A total of 10 919 relevant papers were retrieved, and 59 studies were included. Only 14 studies (23.7%) used standard health economic evaluation methods. Meta-analysis results revealed no significant differences in direct medical expenditure and total expenditure between minimally invasive surgery and open surgery. However, the expenditure for minimally invasive surgery exhibited a significant increase [mean difference ( MD)=5 973.12 yuan, P<0.001], while hospital stay and indirect expenditure significantly decreased ( MD: -4.85 days and -733.79 yuan, P<0.001). In China, for gastric cancer, the direct medical expenditure of endoscopic surgery was lower than that of open surgery ( MD=-33 000.00 yuan) with no significant difference ( P<0.001). In colorectal cancer cases, the direct medical and surgical expenditures for laparoscopic surgery were higher than those for open surgery ( MD: 4 277.94 yuan and 4 267.80 yuan, P<0.001), while the indirect and total medical expenditures decreased ( MD: -768.34 yuan and -159.10 yuan). Hospital stays in patients who had minimally invasive surgery for all three types of cancer were shorter than those who had open surgery ( P<0.001). Conclusions:In the treatment of gastrointestinal cancer, compared with open surgery, minimally invasive surgery shows higher expenditure, but has advantages, such as shorter hospital stay and lower indirect expenditure, and there were no significant differences in direct medical and total expenditures between the two approaches. When conducting health economic evaluation, factors such as postoperative complications, hospital stay, and patient's economic status should be considered for their impact on total medical expenditure. It is necessary to pay attention to the application of health economic evaluations in healthcare decision-making.