Colorectal cancer （CRC） is one of the most common cancers， with its incidence ranking high among cancers. It stands as the second leading cause of cancer-related death worldwide. In the early stages， CRC lacks specific symptoms， and most patients are diagnosed at advanced stages， making it a major research focus in the field of gastrointestinal tumors. Currently， clinical CRC treatments face several common challenges， including high surgical risks， frequent metastasis and recurrence， drug resistance， and significant side effects from chemotherapy and radiation therapy. With the development and application of traditional Chinese medicine （TCM）， it has been found that TCM and its active ingredients can effectively inhibit CRC cell proliferation， invasion， migration， and angiogenesis， and promote apoptosis and autophagy， thereby slowing the progression of CRC. This has become a key focus of CRC treatment research. Salvia Miltiorrhiza has multiple pharmacological effects， including activating blood circulation to dispel blood stasis， unlocking meridians to relieve pain， clearing heat to calm irritability， and cooling blood to reduce abscesses. It contains a variety of chemical components， including diterpenoids， phenolic acids， flavonoids， polysaccharides， nitrogen-containing compounds， steroids， and lactone compounds. This review summarized the molecular mechanisms of Salvia miltiorrhiza and its active ingredients in the treatment of CRC. It is found that these ingredients exert anti-CRC effects through various molecular mechanisms， including cell cycle arrest， promotion of apoptosis， inhibition of cell invasion and migration， induction of autophagy， suppression of tumor angiogenesis， and remodeling of the tumor microenvironment. The review aims to provide new insights for the drug development and clinical application of Salvia miltiorrhiza in CRC treatment.

Objective:To screen differentially expressed genes (DEGs) associated with liver cancer by bioinformatics analysis method, and to investigate the mechanism of the minichromosome maintenance protein 2 ( MCM2) and replication factor C subunit 4 ( RFC4) genes in liver cancer in vitro. Methods:Gene expression profiling data of 80 and 36 hepatocellular carcinoma tissues and 307 and 13 cirrhotic tissues were obtained from the GSE25097 and GSE98620 datasets of the gene expression analysis (GEO) database, respectively. Gene expression profiling data of 374 liver cancer tissues and 50 normal liver tissues were downloaded from the cancer genome atlas (TCGA) database. Limma and DESeqs R software were used to process the gene expression profiling data, construct protein-protein interaction networks, and analysis the relevance of these genes to survival. Weighted gene co-expression network analysis was performed to screen out the core genes. Liver cancer SMMC7721 cells were transfected with MCM2 blank plasmid (MCM2 control group), MCM2 overexpression plasmid [MCM2 WT1 group, MCM2 WT2 (2-fold WT1) group], RFC4 blank plasmid (RFC4 control group), and RFC4 overexpression plasmid [RFC4 WT1 group, RFC4 WT2 (2-fold WT1) group], respectively. The expression of MCM2 and RFC4 in liver cancer cell lines and their transfection levels were detected by real-time fluorescence quantitative reverse transcription PCR and Western blotting. The effects of MCM2 and RFC4 on the proliferation of hepatocellular carcinoma cells were detected by MTT assay and cell cloning assay, respectively. The effects of MCM2 and RFC4 on the migration of liver cancer cells were determined by the scratch assay. The effects of MCM2 and RFC4 on liver cancer cell invasion were detected by Transwell assay.Results:By bioinformatic analysis, 9 HCC DEGs were selected, including ubiquitin conjugating enzyme E2 T ( UBE2T), aurora kinase A ( AURKA), targeting protein for Xklp2 ( TPX2), MCM2, RFC4, ribonucleoside-diphosphate reductase subunit M2 ( RRM2), serine peptidase inhibitory factor Kazal type 1 ( SPINK1), collagen type XV alpha 1 chain ( COL15A1) and C-C motif chemokine 25 ( CCL25). Among the six genes associated with clinical stages, the MCM2 and RFC4 genes were found to be strongly associated with prognosis in liver cancer. The relative protein expression of MCM2 and RFC4 in HepG2 cells (1.83±0.07, 1.44±0.09) and SMMC7721 cells (1.74±0.05, 1.43±0.08) was higher than that in MIHA cells (1.00±0.02, 1.00±0.03), and all the differences were statistically significant (all P<0.05). The relative gene expression of MCM2 and RFC4 in HepG2 cells (14.30±0.12, 5.10±0.18) and SMMC7721 cells (10.60±0.11, 7.60±0.07) was higher than that in MIHA cells (1.00±0.05, 1.00±0.03), and all the differences were statistically significant (all P<0.05). Compared with the MCM2 control group, the absorbance values [(0.28±0.01 and 0.21±0.01) vs 0.18±0.03], the number of clonal cells [(717±12 and 782±29) cells vs (389±17) cells], the percentage migration [(0.43±0.02 and 0.68±0.01) vs 0.15±0.06], and the number of cellular invasions [(933±21 and 821±11) cells vs (409±16) cells] were higher in the MCM2 WT1 and MCM2 WT2 groups, and the differences were all statistically significant (all P<0.05). Compared with the RFC4 control group, the absorbance values [(0.30±0.02 and 0.21±0.01) vs 0.17±0.02], the number of cloned cells [(571±11 and 728±9) cells vs (373±23) cells], the percentage migration [(0.75±0.11 and 0.67±0.04) vs 0.34±0.07], and the number of cell invasion [(835±26 and 818±18) cells vs (629±12) cells] were higher in the RFC4 WT1 and the RFC4 WT2 groups, and the differences were statistically significant (all P<0.05). Conclusions:MCM2 and R FC4 genes play a role in promoting tumorigenesis and growth in hepatocellular carcinoma.

Objective To investigate the therapeutic mechanism of Shen Wu Yizhi Capsule in the treatment of post-stroke cognitive impairment(PSCI)by using network pharmacology methods and clinical trial validation.Methods A prospective trial was carried out in 90 cases of patients with PSCI admitted to Taihe Traditional Chinese Medicine Hospital Affiliated to Anhui University of Chinese Medicine from August 2022 to February 2024.The patients were randomly divided into the control group and the trial group by random number table method,with 45 cases in each group.The control group was treated with conventional treatment for PSCI,and the trial group was treated with Shen Wu Yizhi Capsule orally on the basis of treatment for the control group.The treatment course for the two groups covered 28 days.The changes of Mini-Mental State Examination(MMSE)score,Montreal Cognitive Assessment(MoCA)score,and the serum levels of inflammatory factors such as tumor necrosis factor α(TNF-α)and interleukin 6(IL-6)in the patients of the two groups were observed before and after treatment.Moreover,the incidences of adverse events in the two groups were recorded,thus to evaluate the safety of the treatment regimens in the two groups.And then the network pharmacological research was performed.TCMSP and literature review were used to obtain the active ingredients of Shen Wu Yizhi Capsule,GeneCards and other databases were used to obtain the PSCI disease targets,and the common targets were inputted into the STRING database to construct the PPI network.Cytoscape 3.9.0 was used to construct the network diagram of Shen Wu Yizhi Capsule-PSCI-targets,DAVID was used to perform GO and KEGG pathway enrichment analysis,and then molecular docking was used to verify the binding activity.Results(1)The results of clinical trial showed that after 28 days of treatment,the MMSE and MoCA scores of patients in the two groups were increased compared with those before treatment(P<0.05),and the increase of the scores in the trial group was significantly superior to that in the control group(P<0.05).The serum levels of TNF-α and IL-6 were decreased compared with those before treatment(P<0.05),and the decrease in the trial group was significantly superior to that in the control group(P<0.05).During the trial,both groups of patients did not show obvious adverse reactions,with high safety.(2)The network pharmacological research of Shen Wu Yizhi Capsule yielded 92 active ingredients,803 targets,5 209 disease targets and 556 intersection targets.The core targets were AKT1,TNF,IL-6,TP53 and IL-1B,and the key compounds were deoxyharringtonine,senkyunone and genkwanin.The GO enrichment analysis obtained 1 812 GO entries,of which 154 entries were related with cellular component(CC),1 332 entries were related with biological process(BP),and 326 entries were related with molecular function(MF).The KEGG pathway enrichment analysis yielded 195 signaling pathways.The molecular docking results showed that the key compounds of Shen Wu Yizhi Capsule had good binding activities with the core targets.Conclusion The clinical efficacy of Shen Wu Yizhi Capsule in the treatment of PSCI is remarkable,and its therapeutic mechanism is probably related with multiple components through the signaling pathways such as AKT1,TNF,and IL-6.The results will provide reference for the in-depth study of Shen Wu Yizhi Capsule.

BACKGROUND: Hemorrhagic stroke (HS) is associated with significant disability and mortality. However, the relationship between meteorological factors and hemorrhagic stroke, as well as the potential moderating role of these factors, remains unclear. METHODS: Daily data on HS, air pollution, and meteorological conditions were collected from January 2015 to December 2021 in Ganzhou to analyze the relationship between meteorological factors and HS admissions. This analysis employed a time-stratified case-crossover design in conjunction with a distributional lag nonlinear model. Additionally, a bivariate response surface modelling was utilized to further investigate the interaction between meteorological factors and particulate matter. The study also stratified the analyses by gender and age. To investigate the potential impact of extreme weather conditions on HS, this study defined the 97.5th percentile as representing extremely high weather conditions, while the 2.5th percentile was classified as extremely low. RESULTS: In single-day lags, the risk of admissions for HS was significantly associated with extremely low temperature (lag 1-2 and lag 13-14), extremely low humidity (lag 1 and lag 9-12), and extremely high precipitation (lag 2-7). Females exhibited greater susceptibility to extremely low temperature than males within the single-day lag pattern in the subcomponent layer, with a maximum relative risk (RR) that was 7% higher. In the cumulative lag analysis, the risk of HS admissions was significantly associated with extremely high temperature (lag 0-8∼lag 0-14), extremely low humidity (lag 0-2∼lag 0-14), and extremely high precipitation (lag 0-4∼lag 0-14). Within the cumulative lag day structure of the subcomponent layer, both extremely low and extremely high temperature had a more pronounced effect on females and aged ≥65 years. The risk of HS admissions was positively associated with extremely high barometric pressure in the female subgroups (lag 0-1 and lag 0-2). The highest number of HS admissions occurred when high PM_2.5 concentrations coexisted with low precipitation. CONCLUSIONS Meteorological factors were significantly associated with the risk of hospital admissions for HS. Individuals who were female and aged ≥65 years were found to be more susceptible to these meteorological influences. Additionally, an interaction was observed between airborne particulate matter and meteorological factors. These findings contributed new evidence to the association between meteorological factors and HS.
China/epidemiology* ; Humans ; Female ; Male ; Aged ; Middle Aged ; Cross-Over Studies ; Hospitalization/statistics & numerical data* ; Adult ; Hemorrhagic Stroke/etiology* ; Meteorological Concepts ; Weather ; Particulate Matter/analysis* ; Air Pollution/adverse effects* ; Environmental Exposure/adverse effects* ; Aged, 80 and over ; Young Adult

ObjectiveTo investigate the characteristics and distribution of traditional Chinese medicine （TCM） syndromes in the patients with esophageal squamous cell carcinoma （ESCC）. MethodsAn electronic questionnaire was developed to collect the general data and four examination information of ESCC patients treated in 10 areas with high incidence of esophageal cancer in China from June 2020 to March 2021. Multiple analyses including frequency analysis， factor analysis， and hierarchical cluster analysis were performed to analyze the potential syndrome elements， disease location， and common syndromes of ESCC. ResultsA total of 2 027 patients with ESCC were included. Statistical analysis was performed on 113 symptoms， physical signs， 33 tongue manifestation variables， and 23 pulse manifestation variables of the patients’ four examination information. Factor analysis was performed on 55 variables with frequency>10%， extracting 19 common factors. According to clinical experience and expert opinions， the main lesions of patients with ESCC were in the spleen and stomach， and the main syndrome elements were Qi stagnation， blood stasis， phlegm， dampness， and Qi deficiency， with the syndrome element combination of phlegm obstruction + Qi stagnation + blood stasis being the most common. The syndromes can be classified into four categories of liver-stomach disharmony + combined phlegm and Qi obstruction， kidney-spleen dysfunction + combined phlegm and stasis， spleen-kidney Yang deficiency + obstinate phlegm and blood stasis， and liver-kidney Yin deficiency + obstinate phlegm and blood stasis. The main syndrome of ESCC was liver-stomach disharmony + combined phlegm and Qi obstruction in the early stage， liver-spleen dysfunction + combined phlegm and stasis in the middle stage， and spleen-kidney Yang deficiency + obstinate phlegm and blood stasis in the late stage. ConclusionESCC mainly has main pathological features of internal deficiency and external excess and combined deficiency and excess， with the key syndrome elements being phlegm obstruction， Qi stagnation， and blood stasis. The main disease locations are in the spleen and stomach， involving the liver， kidney， chest and diaphragm， heart， and lung. The main syndrome is liver-stomach disharmony + combined phlegm and Qi obstruction. In clinical practice， it is necessary to grasp the pathogenesis dynamics of the disease and use prescriptions according to patients’ syndromes.

Objective To explore the role and efficacy of VEGF and HGF gene adenovirus vector in promoting angiogenesis in ischemic tissue.Methods 84 Kunming mice were randomly divided into sham group,control group,VEGF group,HGF group and VEGF+HGF group,and the left lower limb ischemia model was established.The blood supply of ischemic tissue was observed by rheometer,and the expression levels of VEGF and HGF in each group were detected by Western Blot and ELISA.Immunohistochemical staining was used to detect angiogenesis(CD31,SMA)in ischemic tissues.Safety was assessed by side effects during treatment in mice.Results After the successful modeling,the blood flow velocity of the left lower limb in each group decreased significantly.On the 7th day after operation,the blood flow of the left lower limb in each group was significantly better than that on the 0th day after operation(P<0.05),and the blood flow of the left lower limb in Ad-VEGF-HGF group was significantly better than that in other groups(P<0.05).On the 28th day after operation,the blood flow of the left lower limb in Ad-VEGF-HGF group gradually stabilized,the blood flow in Ad-VEGF-HGF group was significantly better than that in other groups,and both VEGF group and HGF group were significantly better than the control group(P<0.05).On the 7th,14th,and 28th days following surgery,HGF and VEGF protein levels in the Ad-HGF,Ad-VEGF,and Ad-VEGF-HGF groups were substantially greater than those in the control group(P<0.05).The expression level in the Ad-VEGF-HGF group peaked on the 14th day(all P<0.001)and subsequently declined to preoperative levels on the 28th day after operation.Conclusion Ad-VEGF-HGF gene injection can effectively boost VEGF and HGF protein expression and rapidly reach the relative peak level,encour-aging angiogenesis after lower limb ischemia,increasing blood flow,and improving lower limb circulation.

Objective:To summarize the best evidence of medication adherence interventions for patients with multiple chronic conditions.Methods:According to the "6S" evidence model, literature on medication adherence in patients with multiple chronic conditions was retrieved from BMJ Best Clinical Practice, UpToDate, Medlive, National Institute for Health and Clinical Excellence, Cochrane Library, Embase, PubMed, Web of Science, China Biology Medicine disc, China National Knowledge Infrastructure, WanFang data and so on. The search period was from establishing the database to August 30, 2023.Results:A total of 16 articles were included, including three guidelines, four expert consensus, seven systematic reviews, and two meta-analyses. Twenty-seven pieces of evidence were summarized from six aspects of compliance assessment, educational intervention, behavioral intervention, optimized treatment program, technical reminder intervention, and social-psychological-emotional intervention.Conclusions:The best evidence of medication adherence interventions for patients with multiple chronic conditions summarized provides a reference for medical and nursing staff to develop medication adherence interventions.

Objective:To analyze the clinical characteristics and genetic basis of a male patient with primary infertility caused by Acephalic spermatozoa syndrome.Methods:A patient who had presented at the Henan Provincial People′s Hospital on October 1, 2022 was selected as the study subject. Clinical data and results of laboratory exams and sperm electron microscopy were collected. The patient was subjected to whole exome sequencing (WES), and candidate variants were verified by Sanger sequencing and pathogenicity analysis.Results:WES revealed that the patient has harbored compound heterozygous variants of the PMFBP1 gene, namely c. 853del (p.Ala285Leufs*24) and c. 1276A>T (p.Lys426X), which were both unreported previously. Sanger sequencing suggested that the c. 853del (p.Ala285Leufs*24) variant has derived from his deceased mother, whilst the c. 1276A>T (p.Lys426X) variant has derived from his father. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), both variants were classified as pathogenic (PVS1+ PM2_Supporting+ PP4). Conclusion:The compound heterozygous variants of the PMFBP1 gene probably underlay the Acephalic spermatozoa syndrome in this patient. The discovery of the novel variants has also enriched the mutational spectrum of Acephalic spermatozoa syndrome.

To explore the application value of endoscopic ultrasound fine-needle aspiration (EUS-FNA) and endoscopic retrograde cholangiopancreatography (ERCP) in the diagnosis and treatment ofpatients with pancreatic cancer combined with obstructive jaundice.

Objective: To systematically evaluate the influencing factors for medication compliance in patients with comorbidities of chronic diseases, so as to provide the evidence for improving medication compliance. Methods: Literature on influencing factors for medication compliance in patients with comorbidities of chronic diseases were retrived from CNKI, Wanfang Data, VIP, SinoMed, PubMed, Web of Science, Cochrane Library and Embase from inception to January 20, 2024. After independent literature screening, data extraction, and quality assessment by two researchers, a meta-analysis was performed using RevMan 5.4 and Stata 16.0 softwares. Literature were excluded one by one for sensitivity analysis. Publication bias was assessed using Egger's test. Results: Initially, 7 365 relevant articles were retrieved, and 35 of them were finally included, with a total sample size of about 150 000 individuals. There were 30 cross-sectional studies and 5 cohort studies; and 11 high-quality studies and 24 medium-quality studies. The meta-analysis showed that the demographic factors of lower level of education (OR=2.148, 95%CI: 1.711-2.696), lower economic income (OR=1.897, 95%CI: 1.589-2.264), male (OR=0.877, 95%CI: 0.782-0.985), living alone (OR=2.833, 95%CI: 1.756-4.569) and unmarried (OR=2.784, 95%CI: 1.251-6.196); the medication treatment factors of polypharmacy (OR=1.794, 95%CI: 1.190-2.706), potentially inappropriate medication (OR=2.988, 95%CI: 1.527-5.847), low frequency of daily medication (OR=0.533, 95%CI: 0.376-0.754) and adverse drug reactions (OR=3.319, 95%CI: 1.967-5.602); the disease factors of long course of disease (OR=2.118, 95%CI: 1.643-2.730), more comorbidities (OR=1.667, 95%CI: 1.143-2.431) and cognitive impairment (OR=2.007, 95%CI: 1.401-2.874); and the psychosocial factors of poor belief in taking medication (OR=1.251, 95%CI: 1.011-1.547), poor self-rated health (OR=1.990, 95%CI: 1.571-2.522) and being guided by healthcare professionals (OR=0.151, 95%CI: 0.062-0.368) were the influencing factors for medication compliance in patients with chronic comorbidities. Conclusion The medication compliance in patients with comorbidities of chronic diseases is associated with demographic factors, pharmacological factors, disease factors and psychosocial factors, mainly including living alone, adverse drug reactions, course of disease, number of comorbidities and medication beliefs.