ObjectiveTo investigate the inhibitory effect of Huoluo Xiaolingdan on triple negative breast cancer （TNBC） in mice through its regulation of TCF1⁺CD8⁺ stem cell-like T cells infiltration. MethodsA mouse model of TNBC was established and the mice were randomly divided into the model group， low-dose （3.9 g·kg^-1）， medium-dose （7.8 g·kg^-1） and high-dose （15.6 g·kg^-1） Huoluo Xiaolingdan groups， and anti-PD-1 antibody treatment group. Each group was given a dose of 0.01 mL·g^-1， while the model group and the anti-PD-1 treatment group were also given an equivalent volume of normal saline. The drug was administered for 21 days. In the anti-PD-1 antibody group， mice were intraperitoneally injected with 100 μg of mouse anti-PD-1 antibody twice a week， for a total of five injections. The tumor volume， survival time and tumor mass were measured at different time points. Hematoxylin-eosin （HE） staining was used to observe the histological changes of the tumor. The expression of CD8⁺T cells and TCF1⁺CD8⁺ stem-like T cells in tumor tissues was detected by immunohistochemistry and immunofluorescence staining. Flow cytometry was used to detect the difference of immune cell subsets in tumors and the expression difference of TCF1⁺CD8⁺ stem cell-like T cells in tumors and peripheral blood. The expression level of PD-L1 in tumor tissues was detected by Western blot. ResultsCompared with model group， the tumor volume and mass of in low-， medium- and high-dose Huoluo Xiaolingdan groups and anti-PD-1 group were decreased （P<0.05， P<0.01）. The median survival time of mice in low-， medium- and high-dose Huoluo Xiaolingdan groups and anti-PD-1 group was as follows： 27.00 days （95%CI， 0.45-2.65）， 31.00 days （95%CI， 0.32-1.89）， 34.00 days （95%CI， 0.40-2.33）， and 35.00 days （95%CI， 0.42-2.47）. All of them were higher than that of the model group ［24.50 days （95%CI， 0.37-10.5）］. Flow cytometry showed that compared with the model group， the proportion and number of infiltrating CD8⁺ T cells in tumor were increased in low-， medium- and high-dose Huoluo Xiaolingdan groups and anti-PD-1 group （P<0.05， P<0.01）， while the proportion of tumor regulatory T cells （Treg） and M2 macrophages decreased （P<0.05）. Compared with the model group， the proportion of IFN-γ⁺CD8⁺ T and GrzB⁺CD8⁺ T cells in tumors in low-， medium- and high-dose Huoluo Xiaolingdan groups and anti-PD-1 group was increased （P<0.01）， and the proportion of TCF1⁺CD8⁺ T cells in tumor and peripheral blood was also increased. Immunofluorescence staining further showed that the number of TCF1⁺CD8⁺ T cells in tumor tissues increased in low-， medium- and high-dose Huoluo Xiaolingdan groups. Western blot analysis showed no significant decrease in the PD-L1 protein expression in tumor tissues between the Huoluo Xiaolingdan groups and the model group. ConclusionHuoluo Xiaolingdan can inhibit TNBC in mice by increasing tumor infiltration of TCF1⁺CD8⁺ stem-like T cells， enhancing CD8⁺ T cell activity， and regulating immune cell subgroups such as M2 macrophages and Treg cells to enhance anti-tumor immunity. This study provides a theoretical basis for the clinical application of Huoluo Xiaolingdan in breast cancer treatment and combination therapy.

Lumbar interbody fusion is a surgical method for treating lumbar degenerative diseases. By establishing the stability of the lumbar segment, it solves the related symptoms caused by lumbar degenerative diseases. Minimally invasive transforaminal lumbar interbody fusion(MIS-TLIF) is a mature technology for treating lumbar degenerative diseases and improving the stability of the lumbar segment. In recent years, the emergence of lumbar interbody fusion under the small-channel working tube has made it have more minimally invasive characteristics compared to MIS-TLIF, with smaller incisions, less bleeding, and shorter recovery time. However, due to its long operation time, low efficiency of endplate treatment, and high complications incidence rate, it has not been widely popularized. At present, the large-channel endoscopic system, because of its larger field of view under the endoscope and more efficient endoscopic operation tools, reduces the operation time, improves the efficiency of endplate treatment, and reduces the postoperative related complications incidence rate. According to the surgical approach, it can be divided into transforaminal approach, posterior approach, oblique anterior approach, etc. According to the channel mode, it can also be divided into uniaxial endoscopy and unilateral dual-channel endoscopy, and each has its own advantages and disadvantages. Nowadays, the safety and effectiveness of spinal endoscopic posterior lumbar interbody fusion(Endo-PLIF) under the large-channel have achieved satisfactory results. This article reviews the research progress of Endo-PLIF under the large-channel, including surgical indications and contraindications, anatomical basis, surgical techniques, the choice of cages, the choice of fixation methods, safety and effectiveness, advantages and disadvantages, and explores its clinical application and prospects.

Aim To explore the effect of ginsenoside Rg3 on the biological behavior of human gastric cancer SGC-7901 cells by regulating E2F1.Methods MTT assay was used to determine the effect of ginsenoside Rg3(0,80,160,320 μmol·L-1)on cell prolifera-tion.The effects of different concentrations of ginsen-oside Rg3 on apoptosis were measured by flow cytome-try.The effects of different concentrations of ginsen-oside Rg3 on cell migration and invasion were deter-mined by scratch healing experiment and Transwell ex-periment.The effects of different concentrations of gin-senoside Rg3 on the expression of E2F1,MMP-2,MMP-9,BCL-2 and Bax were determined by Western blot.Results Compared with the blank control group,the cell survival rate of 80,160 and 320 μmol ·L-1 ginsenoside Rg3 group was significantly lower,and it was concentration-dependent(P＜0.05).Com-pared with the blank control group,the apoptosis rate of 80,160 and 320 μmol·L-1 ginsenoside Rg3 group significantly increased in a concentration-dependent manner(P＜0.05).Compared with the blank control group,the number of cell migration in 80,160 and 320 μmol·L-1 ginsenoside Rg3 groups was significantly lower in a concentration-dependent manner(P＜0.05).Compared with the blank control group,the number of cell invasion in 80,160 and 320 μmol· L-1 ginsenoside Rg3 groups was significantly lower in a concentration-dependent manner(P＜0.05).The E2F1 mRNA and E2F1 protein expression in the 80,160,and 320 μmol·L-1 ginsenoside Rg3 groups were significantly reduced in a concentration-dependent manner compared with that in the blank control group(P＜0.05).The protein expression of MMP-2,MMP-9,and BCL-2 in the cells of 80,160,and 320 μmol ·L-1 ginsenoside Rg3 group significantly decreased compared with those of the blank control group,and BCL-2 significantly increased compared with that of the blank control group in a concentration-dependent man-ner(P＜0.05).Conclusions Ginsenoside Rg3 can reduce the proliferation,inhibit the migration and inva-sion of gastric cancer SGC-7901 cells,and promote the apoptosis of SGC-7901 cells in a concentration-depend-ent manner,and its mechanism may be related to the down-regulation of MMP-2,MMP-9,and BCL-2 ex-pression and up-regulation of Bax expression through E2F1.

Objective To explore the treatment of infection after spinal internal fixation.Methods The clinical data of 6 patients with infection after spinal internal fixation in our hospital were analyzed retrospectively.The bacterial culture and drug susceptibility testing were performed to identify the pathogenic bacteria and sensitive antibiotics.Moxifloxacin and/or vancomycin were used empirically for anti-infective therapies first,and then sensitive antibiotics were used according to the results of bacterial culture and drug susceptibility testing.At the same time,imaging examination was performed to determine the infection site and internal fixation,and surgical treatment was decided based on the patients'condition.After operation,the body temperature,inflammatory indexes and drainage of patients were monitored continuously,and the drainage fluid was taken for bacterial culture regularly to evaluate the therapeutic effect.Results The results of bacterial culture in 5 patients were positive and the pathogenic bacteria was staphylococcus aureus,with the susceptibility to vancomycin by susceptibility testing.Among them,1 patient was treated with vancomycin for about 8 weeks because of his advanced age,more basic diseases and high risk of operation;the other 4 patients were received surgery combined with anti-infective treatment with vancomycin for 2 to 4 weeks.One case with negative bacterial culture received surgery combined with anti-infective treatment with imipenem and moxifloxacin.The wound of all patients healed in grade A,the body temperature and inflammatory indexes returned to normal,the low back pain disappeared,and the nerve root symptoms of lower extremities were significantly improved.Conclusion Once the patients with infection after spinal internal fixation are diagnosed,the pathogenic bacterial should be identified as early as possible and sensitive antibiotics should be used.Meanwhile,the internal fixation is removed or re-implanted depending on whether it is infected.

Objective:To explore the role of NK cells in allogeneic hematopoietic stem cell micro-transplantation(MST)in the treatment of patients with acute myeloid leukemia(AML).Methods:Data from 93 AML patients treated with MST at our center from 2013-2018 were retrospectively analyzed.The induction regimen was anthracycline and cytarabine combined with peripheral blood stem cells transplantation mobilization by granulocyte colony stimulating factor(GPBSC),followed by 2-4 courses of intensive treatment with medium to high doses of cytarabine combined with GPBSC after achieving complete remission(CR).The therapeutic effects of one and two courses of MST induction therapy on 42 patients who did not reach CR before transplantation were evaluated.Cox proportional hazards regression analysis was used to analyze the impact of donor NK cell dose and KIR genotype,including KIR ligand mismatch,2DS1,haplotype,and HLA-Cw ligands on survival prognosis of patients.Results:Forty-two patients received MST induction therapy,and the CR rate was 57.1％after 1 course and 73.7％after 2 courses.Multivariate analysis showed that,medium and high doses of NK cells was significantly associated with improved disease-free survival(DFS)of patients(HR=0.27,P=0.005;HR=0.21,P=0.001),and high doses of NK cells was significantly associated with improved overall survival(OS)of patients(HR=0.15,P=0.000).Donor 2DS1 positive significantly increases OS of patients(HR=0.25,P=0.011).For high-risk patients under 60 years old,patients of the donor-recipient KIR ligand mismatch group had longer DFS compared to the nonmismatch group(P=0.036);donor 2DS1 positive significantly prolonged OS of patients(P=0.009).Conclusion:NK cell dose,KIR ligand mismatch and 2DS1 influence the therapeutic effect of MST,improve the survival of AML patients.

Objective:To investigate the clinical features and therapeutic efficacy of patients with hereditary leiomyomatosis and renal cell carcinoma(RCC) syndrome-associated RCC (HLRCC-RCC) in China.Methods:The clinical data of 119 HLRCC-RCC patients with fumarate hydratase (FH) germline mutation confirmed by genetic diagnosis from 15 medical centers nationwide from January 2008 to December 2021 were retrospectively analyzed. Among them, 73 were male and 46 were female. The median age was 38(13, 74) years. The median tumor diameter was 6.5 (1.0, 20.5) cm. There were 38 cases (31.9%) in stage Ⅰ-Ⅱand 81 cases (68.1%) in stage Ⅲ-Ⅳ. In this group, only 11 of 119 HLRCC-RCC patients presented with skin smooth muscle tumors, and 44 of 46 female HLRCC-RCC patients had a history of uterine fibroids. The pathological characteristics, treatment methods, prognosis and survival of the patients were summarized.Results:A total of 86 patients underwent surgical treatment, including 70 cases of radical nephrectomy, 5 cases of partial nephrectomy, and 11 cases of reductive nephrectomy. The other 33 patients with newly diagnosed metastasis underwent renal puncture biopsy. The results of genetic testing showed that 94 patients had FH gene point mutation, 18 had FH gene insertion/deletion mutation, 4 had FH gene splicing mutation, 2 had FH gene large fragment deletion and 1 had FH gene copy number mutation. Immunohistochemical staining showed strong 2-succinocysteine (2-SC) positive and FH negative in 113 patients. A total of 102 patients received systematic treatment, including 44 newly diagnosed patients with metastasis and 58 patients with postoperative metastasis. Among them, 33 patients were treated with tyrosine kinase inhibitor (TKI) combined with immune checkpoint inhibitor (ICI), 8 patients were treated with bevacizumab combined with erlotinib, and 61 patients were treated with TKI monotherapy. Survival analysis showed that the median progression-free survival (PFS) of TKI combined with ICI was 18 (5, 38) months, and the median overall survival (OS) was not reached. The median PFS and OS were 12 (5, 14) months and 30 (10, 32) months in the bevacizumab combined with erlotinib treatment group, respectively. The median PFS and OS were 10 (3, 64) months and 44 (10, 74) months in the TKI monotherapy group, respectively. PFS ( P=0.009) and OS ( P=0.006) in TKI combined with ICI group were better than those in bevacizumab combined with erlotinib group. The median PFS ( P=0.003) and median OS ( P=0.028) in TKI combined with ICI group were better than those in TKI monotherapy group. Conclusions:HLRCC-RCC is rare but has a high degree of malignancy, poor prognosis and familial genetic characteristics. Immunohistochemical staining with strong positive 2-SC and negative FH can provide an important basis for clinical diagnosis. Genetic detection of FH gene germ line mutation can confirm the diagnosis. The preliminary study results confirmed that TKI combined with ICI had a good clinical effect, but it needs to be confirmed by the results of a large sample multi-center randomized controlled clinical study.

Objective:To evaluate the efficacy and safety of antaitasvir phosphate 100 mg or 200 mg combined with yiqibuvir for 12 weeks in patients with various genotypes of chronic hepatitis C, without cirrhosis or compensated stage cirrhosis.Methods:Patients with chronic hepatitis C (without cirrhosis or compensated stage cirrhosis) were randomly assigned to the antaitasvir phosphate 100 mg+yiqibuvir 600 mg group (100 mg group) or the antaitasvir phosphate 200 mg+yiqibuvir 600 mg group (200 mg group) in a 1∶1 ratio. The drugs were continuously administered once a day for 12 weeks and observed for 24 weeks after drug withdrawal. The drug safety profile was assessed concurrently with the observation of the sustained virological response (SVR12) in the two patient groups 12 weeks following the drug cessation. The intention-to-treat concept was used to define as closely as possible a full analysis set, including all randomized cases who received the experimental drug at least once. The safety set was collected from all subjects who received the experimental drug at least once (regardless of whether they participated in the randomization group) in this study. All efficacy endpoints and safety profile data were summarized using descriptive statistics. The primary efficacy endpoint was SVR12. The primary analysis was performed on a full analysis set. The frequency and proportion of cases were calculated in the experimental drug group (antaitasvir phosphate capsules combined with yiqibuvir tablets) that achieved "HCV RNA