This study aims to investigate the therapeutic effect and mechanism of Daotan Xixin Decoction on APP/PS1 mice. Twelve APP/PS1 male mice were randomized into four groups: APP/PS1 and low-, medium-, and high-dose Daotan Xixin Decoction. Three C57BL/6 wild-type mice were used as the control group. The learning and memory abilities of mice in each group were examined by the Morris water maze test. The pathological changes of hippocampal nerve cells were observed by hematoxylin-eosin staining and Nissl staining. Immunohistochemistry was employed to detect the expression of β-amyloid(Aβ)_(1-42) in the hippocampal tissue. The high-dose Daotan Xixin Decoction group with significant therapeutic effects and the model group were selected for high-throughput sequencing. The differentially expressed gene(DEG) analysis, Gene Ontology(GO) analysis, Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analysis, and Gene Set Variation Analysis(GSVA) were performed on the sequencing results. RT-qPCR and Western blot were conducted to determine the mRNA and protein levels, respectively, of some DEGs. Compared with the APP/PS1 group, Daotan Xixin Decoction at different doses significantly improved the learning and memory abilities of APP/PS1 mice, ameliorated the neuropathological damage in the CA1 region of the hippocampus, increased the number of neurons, and decreased the deposition of Aβ_(1-42) in the brain. A total of 1 240 DEGs were screened out, including 634 genes with up-regulated expression and 606 genes with down-regulated expression. The GO analysis predicted the biological processes including RNA splicing and protein folding, the cellular components including spliceosome complexes and nuclear spots, and the molecular functions including unfolded protein binding and heat shock protein binding. The KEGG pathway enrichment analysis revealed the involvement of neurodegenerative disease pathways, amyotrophic lateral sclerosis, and splicing complexes. Further GSVA pathway enrichment analysis showed that the down-regulated pathways involved nuclear factor-κB(NF-κB)-mediated tumor necrosis factor-α(TNF-α) signaling pathway, UV response, and unfolded protein response, while the up-regulated pathways involved the Wnt/β-catenin signaling pathway. The results of RT-qPCR and Western blot showed that compared with the APP/PS1 group, Daotan Xixin Decoction at different doses down-regulated the mRNA and protein levels of signal transducer and activator of transcription 3(STAT3), NF-κB, and interleukin-6(IL-6) in the hippocampus. In conclusion, Daotan Xixin Decoction can improve the learning and memory abilities of APP/PS1 mice by regulating the STAT3/NF-κB/IL-6 signaling pathway.
Animals ; Drugs, Chinese Herbal/administration & dosage* ; Mice ; Male ; Alzheimer Disease/metabolism* ; Computational Biology ; Mice, Inbred C57BL ; High-Throughput Nucleotide Sequencing ; Amyloid beta-Protein Precursor/metabolism* ; Hippocampus/metabolism* ; Mice, Transgenic ; Presenilin-1/metabolism* ; Humans ; Memory/drug effects* ; Maze Learning/drug effects* ; Amyloid beta-Peptides/genetics* ; Disease Models, Animal

OBJECTIVE: To investigate the relationship among seminal oxidation-reduction potential (nORP), sperm DNA fragmentation (DFI) and semen parameters in patients with varicocele. METHODS: Clinical data of 522 patients treated in the reproductive andrology clinic of the Northern Theater General Hospital from November 2023 to December 2023 were retrospectively analyzed, including 435 men of childbearing age and 87 men of infertile age. The patients were divided into the varicocele group (n=116) and non-varicocele group (n=406) according to clinical diagnosis. The differences of seminal plasma nORP, DFI, sperm high DNA stain ability (HDS) and semen parameters were analyzed between the two groups. The relationship among general clinical data, seminal plasma nORP, semen parameters, DFI and HDS in patients with varicocele were further analyzed. According to the severity of varicocele, the patients were divided into three groups, including mild, moderate and severe. And the differences of seminal plasma nORP and semen parameters, DFI and HDS among all groups were analyzed. The differences of seminal plasma nORP, semen parameters, DFI and HDS were compared between the varicocele and non-varicocele groups. RESULTS: The total sperm count, sperm concentration, progressive motility sperm percentage (PR%) and normal sperm morphology rate (NSMR) in patients with varicocele were significantly lower than those in control group (P<0.05). And seminal plasma nORP, DFI and HDS in patients with varicocele were significantly higher than those in control group (P<0.05). Seminal plasma nORP in patients with varicocele was significantly negatively correlated with total sperm, sperm concentration and NSMR (P<0.05), and significantly positively correlated with DFI and HDS (P<0.05). There were significant differences in nORP, total sperm count, sperm concentration, PR%, DFI and HDS among mild, moderate and severe varicocele groups (P<0.05). Seminal plasma nORP, sperm concentration, PR% and DFI in severe group were significantly lower than those in mild and moderate groups(P<0.05). Sperm count and HDS in severe group were significantly lower than those in mild group (P<0.05). In infertile patients, seminal plasma nORP, DFI and HDS in varicocele group were significantly higher than those in control group (P<0.05). And PR% in varicocele group was significantly lower than that in control group (P<0.05). CONCLUSIONS Seminal plasma nORP in patients with varicocele may be an important marker of oxidative stress affecting DFI and semen parameters.
Humans ; Male ; Varicocele/metabolism* ; Semen/metabolism* ; Spermatozoa ; Sperm Count ; Infertility, Male ; Retrospective Studies ; DNA Fragmentation ; Oxidation-Reduction ; Semen Analysis ; Adult ; Sperm Motility

OBJECTIVE: To evaluate the efficacy and safety of Shexiang Tongxin Dropping Pill (STDP) in treating stable angina patients with phlegm-heat and blood-stasis syndrome by exercise duration and metabolic equivalents. METHODS: This multicenter, randomized, double-blind, placebo-controlled clinical trial enrolled stable angina patients with phlegm-heat and blood-stasis syndrome from 22 hospitals. They were randomized 1:1 to STDP (35 mg/pill, 6 pills per day) or placebo for 56 days. The primary outcome was the exercise duration and metabolic equivalents (METs) assessed by the standard Bruce exercise treadmill test after 56 days of treatment. The secondary outcomes included the total angina symptom score, Chinese medicine (CM) symptom scores, Seattle Angina Questionnaire (SAQ) scores, changes in ST-T on electrocardiogram and adverse events (AEs). RESULTS: This trial enrolled 309 patients, including 155 and 154 in the STDP and placebo groups, respectively. STDP significantly prolonged exercise duration with an increase of 51.0 s, compared to a decrease of 12.0 s with placebo (change rate: -11.1% vs. 3.2%, P<0.01). The increase in METs was significantly greater in the STDP group than in the placebo group (change: -0.4 vs. 0.0, change rate: -5.0% vs. 0.0%, P<0.01). The improvement of total angina symptom scores (25.0% vs. 0.0%), CM symptom scores (38.7% vs. 11.8%), reduction of nitroglycerin consumption (100.0% vs. 11.3%), and all domains of SAQ, were significantly greater with STDP than placebo (all P<0.01). The changes in Q-T intervals at 28 and 56 days from baseline were similar between the two groups (both P>0.05). Twenty-five participants (16.3%) with STDP and 16 (10.5%) with placebo experienced AEs (P=0.131), with no serious AEs observed. CONCLUSION STDP could improve exercise tolerance in patients with stable angina and phlegm-heat and blood stasis syndrome, with a favorable safety profile. (Registration No. ChiCTR-IPR-15006020).
Humans ; Double-Blind Method ; Drugs, Chinese Herbal/adverse effects* ; Male ; Female ; Middle Aged ; Angina, Stable/physiopathology* ; Aged ; Syndrome ; Treatment Outcome ; Placebos ; Tablets

OBJECTIVE To evaluate the effects of ABCB1 genotypes on the efficacy and safety of taxanes in the treatment of breast cancer. METHODS By searching Embase，the Cochrane Library， PubMed， CNKI， and Wanfang databases， cohort studies and case-control studies about taxanes in the treatment of breast cancer were collected from the establishment of the database to July 2023. After screeningliterature， extracting data and evaluating quality， meta-analysis was performed by using RevMan 5.3 software. RESULTS A total of 11 studies were included， involving 1 321 patients. There was no correlation between the three genotypes and effective rate， the incidence of myelosuppression， the incidence of neurotoxicity （except for the allele and recessive model of ABCB1 C1236T）， and the incidence of hypersensitivity reactions （P＞0.05）. The subgroup analysis showed that there was a correlation between ABCB1 C1236T dominant model and effective rate when using anthracyclines+5-fluorouracil+cyclophosphamide+taxanes （P＜0.05）， there was a correlation between ABCB1 C3435T recessive model and effective rate when using taxanes+trastuzumab （P＜0.05）. ABCB1 C1236T allele model and recessive model were correlated with sample size ≥100 and using cyclophosphamide+epirubicin+5- fluorouracil+paclitaxel or cyclophosphamide+epirubicin+paclitaxel+trastuzumab or cyclophosphamide+epirubicin+5-fluorouracil+ trastuzumab+paclitaxel regimens； recessive model with sample size ＜100 and the African region were correlated with the incidence of peripheral neuropathy； recessive model was correlated with cutaneous adverse reactions （P＜0.05）. ABCB1 C3435T recessive model was correlated with the incidence of reduced neutrophil count with sample size ≥100； the incidence of white blood cell count reduction with sample size ＜100 and using docetaxel+epirubicin+cyclophosphamide was correlated with both the allele model and the dominant model； the incidence of infections was correlated with the dominant model （P＜0.05）. The incidence of neutrophil count reduction with the sample size ＜100 was correlated with allele model of ABCB1 G2677T/A； the incidence of edema with sample size ≥100 was correlated with allele model and recessive model； the incidence of infection was correlated with allele model and dominant model， especially in patients with neutrophil count complicated with fever （P＜0.05）. CONCLUSIONS ABCB1 genotypes are not correlated with effective rate of taxanes in the treatment of breast cancer， but ABCB1 C3435T genotype is associated with decreased neutrophil counts， decreased white blood cell counts and infections； ABCB1 C1236T genotype is associated with neurotoxicity and cutaneous adverse reactions； ABCB1 G2677T/A genotype is associated with decreased neutrophil counts， infections， and edema.

Femoral neck fracture (FNF) in the elderly patients is currently a major health challenge worldwide, with excessive consumption of medical resources, high incidence of complications as well as suboptimal outcome and prognosis. Hip joint arthroplasty (HJA) has been the mainstream treatment for FNF in the elderly, but the conventional surgical approaches and techniques are still confronted with a series of bottlenecks such as dislocation, limp and limb length discrepancy. In recent years, direct anterior approach (DAA) for HJA (DAA-HJA) has been a major new choice in the field of joint replacement, which achieves improved clinical effectiveness of HJA in the treatment of elderly FNF, due to the fact that DAA approach involves the neuromuscular interface and accords with the idea of soft tissue retention and enhanced recovery after surgery. However, there is still a lack of unified understanding of standard technique and procedure of DAA-HJA in the treatment of elderly FNF. Therefore, relevant experts from the Hip Joint Group of Chinese Orthopedics Association of Chinese Medical Association, Youth Arthrology Group of Orthopedic Committee of PLA, Orthopedic Committee of Chongqing Medical Association, Branch of Orthopedic Surgeons of Chongqing Medical Doctor Association and Sport Medicine Committee of Chongqing Medical Association were organized to formulate the " Chinese expert consensus on the technical standard of direct anterior hip arthroplasty for elderly femoral neck fracture ( version 2023)" based on evidence-based medicine. This consensus mainly proposed 13 recommendations covering indications, surgical plans, prosthesis selections, surgical techniques and processes, and postoperative management of DAA-HJA in elderly patients with FNF, aiming to promote standardized, systematic and patient-specific diagnosis and treatment to improve the functional prognosis of the patients.

Traditional Chinese medicine （TCM） is a great treasure house， exhibiting unique advantages in the treatment of some difficult and critical diseases. The incidence rate of membranous nephropathy has increased year by year in recent years， and has become the first cause of primary glomerular diseases. However， its pathogenesis is not clear. Modern medicine often uses immunosuppressive therapy， but it often faces the problems of high side effects and high recurrence rate. The China Association of Chinese Medicine （CACM） invited clinical experts of TCM and western medicine to fully discuss membranous nephropathy， which was later confirmed to be one of the clinical diseases responding specifically to TCM. Apart from summarizing the pathogenesis and clinical diagnosis and treatment of membranous nephropathy in both TCM and western medicine， this paper also detailed TCM cognition， syndrome differentiation， and therapeutic schemes of membranous nephropathy， aiming to improve the clinical remission rate of membranous nephropathy and provide reference for its clinical treatment.

Polypyrimidine tract-binding protein 1 (PTBP1) plays an essential role in splicing and is expressed in almost all cell types in humans, unlike the other proteins of the PTBP family. PTBP1 mediates several cellular processes in certain types of cells, including the growth and differentiation of neuronal cells and activation of immune cells. Its function is regulated by various molecules, including microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and RNA-binding proteins. PTBP1 plays roles in various diseases, particularly in some cancers, including colorectal cancer, renal cell cancer, breast cancer, and glioma. In cancers, it acts mainly as a regulator of glycolysis, apoptosis, proliferation, tumorigenesis, invasion, and migration. The role of PTBP1 in cancer has become a popular research topic in recent years, and this research has contributed greatly to the formulation of a useful therapeutic strategy for cancer. In this review, we summarize recent findings related to PTBP1 and discuss how it regulates the development of cancer cells.
Alternative Splicing ; Carcinogenesis ; Glycolysis ; Heterogeneous-Nuclear Ribonucleoproteins/physiology* ; Humans ; MicroRNAs/physiology* ; Neoplasms/pathology* ; Polypyrimidine Tract-Binding Protein/physiology* ; RNA, Long Noncoding/physiology*

Objective: To study the sesquiterpenes from the roots of Vladimiria souliei. Methods: The compounds were isolated by silica gel, Sephadex LH-20, medium pressure chromatographic column, preparative-TLC, and preparative-HPLC. And their structures were identified by means of chemical methods and spectroscopic analyses. Results: Nine compounds were isolated from V. souliei, and named as 15-acetoxy-11αH-germacra-1(10)E, 4E-diene-12, 6α-olide (1), 15-acetoxy-11βH-germacra-1(10)E, 4E-diene-12, 6α-olide (2), 12-hydroxy-5α(H), 7α(H)-eudesm-4(14), 11(13)-diene-9-one (3), oplodiol (4), dihydroestafiatone (5), 10-oxo-dihydroxy-11β, 13-dihydrode hydrocostuslactone (6), (11S)-13-hydroxyl-guaia-4(15), 10(14)-diene-12, 6α-olide (7), 9-oxonerolidol (8), and vernopolyanthone (9). Conclusion: Compounds 1 and 3 are new compounds, named as vlasoudide and vlasoudione; and compounds 4-9 are isolated from the roots of V. souliei for the first time.

Objective To study the influence of the small interfering RNA (siRNA) interference TMPRSS4 expression on human pancreatic cancer SW1990 cell's proliferation and invasion. Methods The four eukaryotic expression vector of TMPRSS4 gene were synthesized in vitro and were transfected transiently into human pancreatic cancer SW1990 cells. TMPRSS4 mRNA expression of transfected cells was detected by real-time RT-PCR. The most efficient eukaryotic expression vector was used to be transfected into SW1990 cells. By using G418, cell strain that can silence TMPRSS4 gene stably was screened. The TMPRSS4 mRNA expression of the stable cell strain was detected by real time PCR TMPRSS4 protein expression was detected by western blot. The proliferation ability of transfected SW1990 cells was detected by CCK-8 method. By Transwell, the invasion change of SW1990 cell was detected. Results A stable cell strain, SW1990/psi TMPRSS4, was successfully constructed, in which the expression level of TMPRSS4 could be reduced stably by RNA interference. Cell transfection efficiency was 82.9%. Compared with the control group, the TMPRSS4 mRNA and protein levels were reduced by 80.1% and 60% ,and number of penetrating cells was 118.6 ±13.4 in SW1990/psi TMPRSS4 group, which was significantly lower than those in the negative control group (157.4 ± 12.9) and control group (157.0±9.5, P <0.01). Cells invasion inhibitory rate was 24.5% in SW1990/psi TMPRSS4 group. The cell proliferation was not significantly different among all the groups. Conclusions A stable cell strain is screened successfully in which the expression level of TMPRSS4 can be reduced stably. The down-regulation of TMPRSS4 gene expression level can inhibit the invasion of SW1990 cells, but has no effect on cell proliferation.

Objective To evaluate the factors influencing early diagnosis and prognosis in patients with pancreatic carcinoma.Methods The clinical data of 280 patients who had complete follow-up data with pancreatic carcinoma treated from January 2002 to January 2007 were reviewed retrospectively.The medical history and follow-up data were collected from all patients.Survival rate was calculated by the life table method and the Kaplan-Meier estimation.Log-rank test was used for univariate prognostic analysis and Cox regression was used for multivariate prognostic analysis.Results 91.8%of the patients were more than 40 years old and the peak age was 50～73 years old;the major presentations were abdominal pain and jaundice.Major imaging tests included B-ultrasound and CT,the sensitivity was 70.6%,95.3%,respectively;89.3%of patients had combined B-ultrasound and CT examination.The sensitivity of CA19-9 was 81.1%.The median survival time was(7.0±0.5)months.Overall survival rates at 1～5 year survival rates were 28%,9%,6%,2%,and 1%.Univariate analysis suggested that age＞65 years old,CA19-9＞mean value,TNM Ⅲ or Ⅳ stage,lymph nodes invasion,vascular invasion,and metastasis of two or more organs,non-surgical treatment,KPS score＜60 points,weight loss≥5 kg were poor prognostic factors;Cox multivariate analysis showed that treatment modalities,age,TNM stage,KPS score and ascites were independent risk factors for dismal prognosis.Conclusions The age,ascites,tumor stage and treatment modalities affected the prognosis of patients with pancreatic cancer.Early diagnosis and treatment was important to improve the survival time of patients with pancreatic cancer.