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 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 investigate the relationship among seminal oxidation-reduction potential(nORP),sperm DNA frag-mentation(DFI)and semen parameters in patients with varicocele.Methods:Clinical data of 522 patients treated in the reproduc-tive andrology clinic of the Northern Theater General Hospital from November 2023 to December 2023 were retrospectively analyzed,in-cluding 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 varico-cele,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 concentra-tion,progressive motility sperm percentage(PR％)and normal sperm morphology rate(NSMR)in patients with varicocele were sig-nificantly lower than those in control group(P＜0.05).And seminal plasma nORP,DFI and HDS in patients with varicocele were sig-nificantly 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.

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.

Objective:To investigate the association between the local renin-angiotensin system (RAS) in human follicular fluid (hFF) and age, ovarian function, in vitro fertilization (IVF) laboratory outcome. Methods:A non-intervention observational study was designed. hFF and medical case history without personal identity of patients who received IVF simply because of male factor infertility in Reproductive Medicine Center, the First Affiliated Hospital of Soochow University during January 2021 and February 2022 were collected. The renin, angiotensin converting enzyme (ACE), ACE2, angiotensin (Ang)Ⅱ and Ang 1-7 levels were detected by enzyme-linked immunosorbent assay kit. The correlation between age and RAS in hFF was analyzed by simple linear regression, and multivariate linear regression was used to further analyze the correlation between the RAS and IVF laboratory outcome.Results:1) A total of 139 samples of analysable hFF were obtained. 2) There was a linear negative correlation between age and renin (Pearson's r=-0.313 3, P<0.001), angiotensin converting enzyme (ACE; Pearson's r=-0.183 6, P=0.031), angiotensinⅡ (AngⅡ; Pearson's r=-0.218 6, P=0.010), ACE/ACE2 (Pearson's r=-0.319 2, P<0.001), AngⅡ/Ang1-7 (Pearson's r=-0.224 3, P=0.008), while the linear relationship with ACE2 and Ang1-7 was not significant (all P>0.05). 3) Basal follicle-stimulating hormone was positively correlated with age ( β=0.636, P<0.001), ACE2 ( β=0.267, P=0.026) and AngⅡ ( β=0.268, P=0.001), while negatively correlated with ACE ( β=-0.320, P<0.001) and Ang1-7 ( β=-0.217, P=0.014). Basal luteinizing hormone was positively correlated with AngⅡ ( β=0.330, P=0.003), while negative correlated with Ang1-7 ( β=-0.395, P=0.002). Antral follicle count was positively correlated with Ang1-7 ( β=0.153, P=0.049), while negatively correlated with age ( β=-0.869, P<0.001) and ACE2 ( β=-0.082, P=0.004). Basal anti-Müllerian hormone was only negatively correlated with age ( β=-0.349, P<0.001). There was no correlation between RAS and basal estradiol, progesterone, prolactin, testosterone (all P>0.05). 4) Oocyte retrieval count was positively correlated with renin ( β=0.146, P=0.014), AngⅡ ( β=0.113, P=0.034) and Ang1-7 ( β=0.185, P=0.002), while negatively correlated with age ( β=-0.717, P<0.001); MⅡ oocyte maturation rate was positively correlated with AngⅡ ( β=0.207, P=0.019) and Ang1-7 ( β=0.217, P=0.026), while negatively correlated with age ( β=-0.518, P<0.001). There was no correlation between RAS and the rates of two pronuclei embryos, transplantable embryos, high-quality embryos (all P>0.05). Conclusion:The local RAS in ovarian follicles is affected by age and correlated with ovarian function and IVF laboratory outcome.

The rapid development of reproductive medicine has made outstanding contribution to the solution of population problem, but it still cannot satisfy all couples to become "complete parents" at the genetic level. As research progressed of regenerative medicine, it is found that the stem cells have the characteristics of promoting endogenous repair, improving oxidative stress level, regulating immune microenvironment, and so on. Therefore, the transplantation of stem cells is considered to be a new and effective therapy to restore the damaged reproductive function. The mesenchymal stem cells are considered as an ideal source for transplantation therapy because of the characteristics of wide source, easy acquisition and low immunogenicity. Furthermore, it has been proven effective in a large number of scientific and clinical researches in the reproductive field. This paper reviews the basic research progress on all kinds of mesenchymal stem cells in the field of reproductive medicine at home and abroad.

Objective:To investigate the association between the local renin-angiotensin system (RAS) in human follicular fluid (hFF) and age, ovarian function, in vitro fertilization (IVF) laboratory outcome. Methods:A non-intervention observational study was designed. hFF and medical case history without personal identity of patients who received IVF simply because of male factor infertility in Reproductive Medicine Center, the First Affiliated Hospital of Soochow University during January 2021 and February 2022 were collected. The renin, angiotensin converting enzyme (ACE), ACE2, angiotensin (Ang)Ⅱ and Ang 1-7 levels were detected by enzyme-linked immunosorbent assay kit. The correlation between age and RAS in hFF was analyzed by simple linear regression, and multivariate linear regression was used to further analyze the correlation between the RAS and IVF laboratory outcome.Results:1) A total of 139 samples of analysable hFF were obtained. 2) There was a linear negative correlation between age and renin (Pearson's r=-0.313 3, P<0.001), angiotensin converting enzyme (ACE; Pearson's r=-0.183 6, P=0.031), angiotensinⅡ (AngⅡ; Pearson's r=-0.218 6, P=0.010), ACE/ACE2 (Pearson's r=-0.319 2, P<0.001), AngⅡ/Ang1-7 (Pearson's r=-0.224 3, P=0.008), while the linear relationship with ACE2 and Ang1-7 was not significant (all P>0.05). 3) Basal follicle-stimulating hormone was positively correlated with age ( β=0.636, P<0.001), ACE2 ( β=0.267, P=0.026) and AngⅡ ( β=0.268, P=0.001), while negatively correlated with ACE ( β=-0.320, P<0.001) and Ang1-7 ( β=-0.217, P=0.014). Basal luteinizing hormone was positively correlated with AngⅡ ( β=0.330, P=0.003), while negative correlated with Ang1-7 ( β=-0.395, P=0.002). Antral follicle count was positively correlated with Ang1-7 ( β=0.153, P=0.049), while negatively correlated with age ( β=-0.869, P<0.001) and ACE2 ( β=-0.082, P=0.004). Basal anti-Müllerian hormone was only negatively correlated with age ( β=-0.349, P<0.001). There was no correlation between RAS and basal estradiol, progesterone, prolactin, testosterone (all P>0.05). 4) Oocyte retrieval count was positively correlated with renin ( β=0.146, P=0.014), AngⅡ ( β=0.113, P=0.034) and Ang1-7 ( β=0.185, P=0.002), while negatively correlated with age ( β=-0.717, P<0.001); MⅡ oocyte maturation rate was positively correlated with AngⅡ ( β=0.207, P=0.019) and Ang1-7 ( β=0.217, P=0.026), while negatively correlated with age ( β=-0.518, P<0.001). There was no correlation between RAS and the rates of two pronuclei embryos, transplantable embryos, high-quality embryos (all P>0.05). Conclusion:The local RAS in ovarian follicles is affected by age and correlated with ovarian function and IVF laboratory outcome.

The rapid development of reproductive medicine has made outstanding contribution to the solution of population problem, but it still cannot satisfy all couples to become "complete parents" at the genetic level. As research progressed of regenerative medicine, it is found that the stem cells have the characteristics of promoting endogenous repair, improving oxidative stress level, regulating immune microenvironment, and so on. Therefore, the transplantation of stem cells is considered to be a new and effective therapy to restore the damaged reproductive function. The mesenchymal stem cells are considered as an ideal source for transplantation therapy because of the characteristics of wide source, easy acquisition and low immunogenicity. Furthermore, it has been proven effective in a large number of scientific and clinical researches in the reproductive field. This paper reviews the basic research progress on all kinds of mesenchymal stem cells in the field of reproductive medicine at home and abroad.

Recent studies suggest that recompensation of liver function appears in decompensated cirrhosis after effective treatment. However, liver function recompensation degree, recompensation evaluation diagnostic criteria, how to predict recompensation from the perspective of liver function, and others still need to be further explored. Therefore, functional recompensation is explored here from the perspective of decompensated-stage cirrhosis.
Humans ; Liver Cirrhosis ; Treatment Outcome

OBJECTIVE: To explore whether the ethanol extract of Herpetospermum caudigerum Wall (EHC), a Xizang medicinal plant traditionally used for treating liver diseases, can improve imiquimod-induced psoriasis-like skin inflammation. METHODS: Immunohistochemistry and immunofluorescence staining were used to determine the effects of topical EHC use in vivo on the skin pathology of imiquimod-induced psoriasis in mice. The protein levels of interferon-γ (IFN-γ), tumor necrosis factor-α (TNF-α), and interleukin-17A (IL-17A) in mouse skin samples were examined using immunohistochemical staining. In vitro, IFN-γ-induced HaCaT cells with or without EHC treatment were used to evaluate the expression of keratinocyte-derived intercellular cell adhesion molecule-1 (ICAM-1) and chemokine CXC ligand 9 (CXCL9) using Western blotting and reverse transcription-quantitative polymerase chain reaction. The protein synthesis inhibitor cycloheximide and proteasome inhibitor MG132 were utilized to validate the EHC-mediated mechanism underlying degradation of ICAM-1 and CXCL9. RESULTS: EHC improved inflammation in the imiquimod-induced psoriasis mouse model and reduced the levels of IFN-γ, TNF-α, and IL-17A in psoriatic lesions. Treatment with EHC also suppressed ICAM-1 and CXCL9 in epidermal keratinocytes. Further mechanistic studies revealed that EHC suppressed keratinocyte-derived ICAM-1 and CXCL9 by promoting ubiquitin-proteasome-mediated protein degradation rather than transcriptional repression. Seven primary compounds including ehletianol C, dehydrodiconiferyl alcohol, herpetrione, herpetin, herpetotriol, herpetetrone and herpetetrol were identified from the EHC using ultra-performance liquid chromatography-quadrupole-time of flight-mass spectrometry. CONCLUSION Topical application of EHC ameliorates psoriasis-like skin symptoms and improves the inflammation at the lesion sites. Please cite this article as: Zhong Y, Zhang BW, Li JT, Zeng X, Pei JX, Zhang YM, Yang YX, Li FL, Deng Y, Zhao Q. Ethanol extract of Herpetospermum caudigerum Wall ameliorates psoriasis-like skin inflammation and promotes degradation of keratinocyte-derived ICAM-1 and CXCL9. J Integr Med. 2023; 21(6): 584-592.
Animals ; Mice ; Interleukin-17/metabolism* ; Intercellular Adhesion Molecule-1 ; Imiquimod/adverse effects* ; Tumor Necrosis Factor-alpha/metabolism* ; Ligands ; Psoriasis/chemically induced* ; Keratinocytes ; Inflammation/drug therapy* ; Chemokines/metabolism* ; Interferon-gamma/metabolism* ; Disease Models, Animal ; Mice, Inbred BALB C