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.

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.

Colorectal cancer (CRC) is a common malignancy burdening people globally, with increasing morbidity and mortality nowadays, due to the alternation in the diet type and lifestyle in modern society. Berberine, a type of benzylisoquinoline alkaloid, is widely present in numerous medicinal plants, particularly including Coptidis Rhizoma. Mounting evidence reveals that berberine possesses an array of pharmacological effects, such as anti-inflammation, anti-bacterium, anti-cancer, anti-diabetes mellitus and so on. In particular, berberine exhibits substantial inhibition on various types of cancers including CRC. Hereby, we sought to systematically review the suppressive effect of berberine on CRC through the diminishment of the proliferation and metastasis, induction of apoptosis, arrest of cell cycle, regulation of inflammatory reaction, the reverse of chemotherapeutic resistance and restoration of gut microbiota in CRC, so as to shed light on the in-depth mechanisms underlying the treatment of CRC with berberine in the clinical setting.

DNA ; DNA Fingerprinting ; Homicide ; Humans

OBJECTIVE To investigate the therapeutic effect of scutellarin on colitis-associated cancer (CAC) and its underlying mechanism based on Wnt/β-catenin signaling pathway. METHODS The mouse model of CAC was estab?lished by azomethane oxide (AOM) and sodium dextran sulfate (DSS), followed by scutellarin treatment, with recording the body weight, diarrhea and hematochezia. After sacrificing the mice, the colorectal length and colorectal tumor were assessed. The levels of pro-inflammatory factors TNF-α and IL-6 in mice's sera were measured by the enzyme-linked immunosorbent assay (ELISA). The colorectal lesions were appraised by hematoxylin and eosin (H&E) staining. Theβ-catenin level in CAC tissues was probed by immunofluorescent analysis. The apoptosis-related genes Bax and Bcl-2, and Wnt signaling pathway-related genes β-catenin, GSK-3β, TCF4, c-Myc and cyclin D1 were detected by real-time quantitative RT-PCR (RT-qPCR). Finally, Western blotting analysis (WB) was employed to examine the expressions of the apoptosis and Wnt signaling pathway-related proteins. RESULTS Scutellarin significantly improved AOM/DSS-caused weight loss, colorectal length shortening, and tumor growth in mice (P<0.01). Meanwhile, colorectal lesions could be substantially alleviated by scutellarin. ELISA results showed that the levels of pro-inflammatory factors TNF-αand IL-6 were drastically lessened (P<0.01). Scutellarin also sharply inhibited the nuclear translocation of β-catenin, as evidenced by the reduction in the nuclear level ofβ-catenin protein. In addition, scutellarin attenuated the mRNA expres?sion of Wnt signaling pathway-relatedβ-catenin, TCF4, c-Myc and cyclin D1, whereas it heightened GSK-3βmRNA level. These results were consolidated by WB analysis, which indicated that scutellarin could mitigate the protein levels of phospho-GSK-3β,β-catenin, TCF4, c-Myc and cyclin D1, with the increase in GSK-3β protein in CAC tissue. Moreover, scutellarin could induce the apoptosis of CAC, demonstrated by enhanced expression of Bax and diminished expression of Bcl-2 in both mRNA and protein levels. CONCLUSION Scutellarin may ameliorate colitis-associated colorectal cancer by weakening Wnt/β-catenin signaling cascade.

OBJECTIVE To identify the inhibitory effect of ursolic acid on the colorectal cancer HCT116 cells in vitro and in vivo, and to explore the underlying mechanism. METHODS The smoothened (SMO) gene-silenced human colorectal cancer HCT116hSMO- cell line was established by transfection with the lentivirus carrying SMO shRNA. The cytotoxic effect of ursolic acid on HCT116hSMO-cells was determined by MTT assay. The effect of ursolic acid on the migration of HCT116hSMO- cells was studied by wound healing assay. The effect of ursolic acid on apoptosis of HCT116hSMO-cells was explored by Hoechst33342/PI double staining and flow cytometry. The effects of ursolic acid on the expressions of apoptotic marker gene Bcl-2, Bax, caspase-3 and caspase-9 were measured by real-time quantitative RT-PCR (RT-qPCR) and Western blotting (WB) analysis. RT-qPCR and WB were used to examine the relationship between GLI1, c-Myc expression and PI3K/Akt pathway to further investigate the mechanism of GLI1 activation in HCT116hSMO- cells. The effects of ursolic acid on the expressions of GLI1, p-Akt, Akt, c-Myc, SHH and SUFU of nonca?nonical Hedgehog pathway were evaluated by RT-qPCR and WB assays. Xenograft nude mouse model bearing HCT116hSMO- cells was established and intraperitoneally treated with ursolic acid to investigate the effect on tumor growth in vivo. The body weight and tumor size of mice were assessed regularly every 2 d. The effect of ursolic acid on the apoptosis of tumor tissue was determined by TUNEL assay. The expressions of Bcl-2, Bax, GLI1, p-Akt, Akt, c-Myc, SHH, SUFU mRNA and proteins were measured by RT-qPCR and WB. The levels of Bcl-2, Bax, GLI1, p-Akt, c-Myc and SHH proteins in tumor tissues were also evaluated by immunohistochemistry. RESULTS Ursolic acid significantly inhibited the growth and migration of HCT116hSMO-cells in vitro, compared with the control (P<0.05). Meanwhile, ursolic acid also induced apoptosis of HCT116hSMO- cells in vitro (P<0.05). Furthermore, SC79 (Akt activator) enhanced the expressions of p-Akt, GLI1 and c-Myc, which could be abolished by ursolic acid, and the effect was equal to Akt inhibitor LY294002. The expressions of Bcl-2, GLI1, p-Akt, c-Myc, SHH mRNA and proteins were reduced by ursolic acid, while the levels of Bax and SUFU were increased. Ursolic acid could inhibit the growth and induce the apoptosis of colorectal cancer xeno?graft in vivo. Similarly, lower levels of Bcl-2, GLI1, p-Akt, c-Myc and SHH, and higher expression of Bax and SUFU were noted in ursolic acid-treated mice. CONCLUSION Ursolic acid can inhibit the growth and induce apoptosis of HCT116hSMO- cells both in vitro and in vivo. And the mechanism is related to the suppression of PI3K/Akt-mediated noncanonical Hedgehog signaling pathway.

Pulsatilla chinensis is a widely used traditional Chinese herb, which contains 56 types of chemical constit?uents, mainly including triterpenoid saponins, organic acids, coumarins and lignans. The largest portion of the ingredi?ents in Pulsatilla chinensis is the family of triterpenoid saponins, in which anemoside B4 is the major effective compound and indexing component. The main components of Pulsatilla chinensis can metabolize into a vast array of active prod?ucts in vivo, which play vital roles in its biological activity. Mounting evidence reveals that Pulsatilla chinensis exerts a wide range of therapeutic activities, such as anti-cancer, immunoregulation, anti-inflammation and anti-schistosome, with fewer adverse reactions, via various signaling pathways and multiple targets. It was documented that the active ingre?dient of Pulsatilla chinensis can lessen the drug resistance and synergize the effects of other natural products includ?ing paclitaxel, as well as ameliorate the clinical efficacy of chemical drugs, such as adriamycin. However, Pulsatilla chi?nensis was also reported to be possibly the main cause of hemolysis and chronic liver injury. The efforts should be made to deeply investigate the pharmacological actions and underlying mechanisms of Pulsatilla chinensis, with a focus on the anti-cancer efficacy, and develop new drugs based on the components of Pulsatilla chinensis for future utilization in the clinical setting.

Oleanolic acid (OA) is a pentacyclic triterpenoid chemical component that exists in natural plants with a molecular formula of C30H48O3 and a molecular weight at 456.71 g·mol-1. OA is widespread in traditional Chinese herbal medicine (Ligustri Lucidi Fructus, Achyranthis Bidentate Radix, Red Sage) and berries (blueberries, grapes). In recent years, because of the extensive pharmacological effects of OA, its advantages in disease treatment have become increasingly prominent and gradually attracted the attention of pharmaceutical researchers. OA has effective therapeutic effects on a series of chronic diseases such as inflammation, cancer, diabetes, and cardiovascular diseases through mul?tiple signaling pathways and various targets. Especially in cancers, such as colorectal cancer, liver cancer, gastric cancer, lung cancer, breast cancer and other malignancies, OA presents substantial efficacy. However, its poor aqueous solubility, needy bioavailability, and unsatisfactory pharmacological activity excessively restrict its clinical application. More impor?tantly, the improper utilization of OA can cause adverse reactions, toxic effects and even damage to organs in some spe?cific situations. With the discovery of various pharmacological effects, the complex action mechanisms of OA, the contin?uous progress in structural modification of OA, as well as the synthesis of OA derivatives, its application is expand?ing gradually. Among numerous studies, there is a clear indication that OA and its derivatives, if fully developed, may provide an alternative and cheaper treatment for a variety of chronic diseases. However, the specific molecular mecha?nisms of OA and its derivatives as an alternative therapy and supplementary therapy for cancer, diabetes, cardiovascular disease and other chronic diseases remain to be clarified. Therefore, it is necessary to further study the pharmacokinet?ics, pharmacological activity, specific targets and related mechanisms of OA to lay a solid foundation for drug devel?opment and the application of OA in clinical settings.

OBJECTIVE To investigate the inhibition and mechanism of berberine on human colorectal cancer HCT116 cells through canonical Hedgehog signaling pathway. METHODS The effect of berberine on cell morphology was observed by microscopy. MTT colorimetric assay, cell scratch experiment, colony formation assay and Hoechest/PI staining were utilized to detect the activities of berberine on cell viability, cell migration and cell apoptosis. Flow cytome?try was applied to examine the cell apoptosis. The effects of berberine on caspase-3 and caspase-9 were detected by caspase activity detection kit. The expressions of Hedgehog signaling pathway-related proteins SHH, GLI1, PTCH1, SMO, SUFU, apoptosis-related proteins Bax and Bcl-2 as well as cell cycle-related proteins cyclin D1 were detected by Western blotting. Additionally, quantitative real time RT-PCR was employed to assess the mRNA expression levels of Hedgehog signaling pathway-related genes SHH, GLI1, PTCH1, SMO, SUFU, apoptosis-related genes Bax and Bcl-2 as well as cell cycle-related genes cyclin D1. RESULTS Berberine sharply altered the morphology of human colorectal cancer HCT116 cells, demonstrated by that migration ability of HCT116 cells was reduced significantly and the nuclei were densely stained. Berberine could induce apoptosis in a dose-dependent manner. The activities of caspase-3 and caspase-9 were increased prominently. The expression levels of Hedgehog signaling pathway-related protein SUFU and apoptosis-related protein Bax were augmented substantially. The expression levels of Hedgehog signaling pathway-related proteins SHH, GLI1, PTCH1, SMO, apoptosis-related protein Bcl-2 as well as cell cycle-related genes cyclin D1 were markedly lessened. Besides, the mRNA expression levels of Hedgehog signaling pathway-related gene SUFU and apoptosis-related gene Bax were augmented substantially. The mRNA expression levels of Hedgehog signaling path?way-related genes SHH, GLI1, PTCH1, SMO, apoptosis-related gene Bcl-2 as well as cell cycle-related gene cyclin D1 were markedly lessened. CONCLUSION Berberine, which is the main component of coptidis rhizoma, can remarkably restrain the growth and proliferation, promote apoptosis of human colorectal cancer cells HCT116, and the underlying mechanism may be involved in suppressing the activity of the Hedgehog signaling pathway.