Objective:To investigate immunotherapy effects and mechanism of BCG and recombinant BCG(rBCG)with c-di-AMP as adjuvant on melanoma in mice model.Methods:Melanoma mice model was established by B16F10 cell subcutaneous injec-tion in groin,and treated with 1×106 CFU of BCG and rBCG by adjacent injection of subcutaneous tumor for 3 times,respectively.Survival of melanotic mice,tumor growth and metastasis were observed.Tumor tissues of mice were isolated to prepare cell suspen-sion,and proportion of immune cells were detected by flow cytometry.Transcriptional levels of immune-related genes in tumor tissues were detected by qRT-PCR.Results:Both BCG and rBCG immunotherapy could significantly inhibit growth in melanoma mice and prolong survival time of mice.rBCG showed better inhibition on metastasis than BCG.Both strains significantly reduced proportion of M2-type macrophages and myeloid-derived suppressor cell associated with tumor growth and metastasis.Both two strains promoted infiltration of lymphocytes in tumor tissues,and rBCG significantly increased proportion of B cells in tumor.BCG immunotherapy upregulated transcription levels of metastasis-related cytokines,while rBCG therapy had no effects on transcriptions of these genes.Conclusion:Both BCG and rBCG have immunotherapeutic effects on melanotic mice,and rBCG with c-di-AMP as adjuvant shows better inhibition on tumor metastasis than BCG,which mechanism was related to regulation of immune response in tumor tissues.

Oral squamous cell carcinoma (OSCC) is a malignant tumor that seriously threatens human health. Its typical biological characteristics include strong local invasiveness, high lymph node metastasis rate, and high recurrence rate after treatment. Hepatocyte growth factor (HGF), cellular-mesenchymal to epithelial transition factor (c-Met), and the HGF/c-Met signaling pathway are involved in the regulation of the occurrence and development of OSCC. HGF and c-Met proteins are overexpressed in OSCC, and multiple studies have suggested that they are significantly associated with the malignant characteristics of tumors and poor prognosis. Furthermore, the abnormal activation of the HGF/c-Met signaling pathway (driven by HGF-dependent autocrine/paracrine or non-dependent mechanisms such as MET gene mutations, amplification, fusion, and protein overexpression) can synergistically promote tumor cell invasion, metastasis, and angiogenesis by activating downstream signaling pathways. However, HGF/c-Met can also mediate immune escape by promoting lactate secretion increase, inducing programmed death ligand 1 (PD-L1) expression upregulation, activating and expanding myeloid-derived suppressor cells, and promoting the proliferation of regulatory T cells (Tregs). In addition, the crosstalk between the HGF/c-Met signaling pathway and key pathways such as phosphatidylinositide 3-kinases (PI3K)/protein kinase B (AKT), epidermal growth factor receptor (EGFR), Janus kinase (JAK)/signal transducer and activator of transcription (STAT3), and non-coding RNAs can also promote tumor progression. Currently, three types of targeted drugs have been developed targeting the HGF/c-Met pathway: HGF monoclonal antibody, c-Met monoclonal antibody, and tyrosine kinase inhibitors. Some of these drugs have entered clinical trials. However, the emergence of drug resistance during treatment, especially the bidirectional compensatory activation of alternative signaling pathways such as EGFR, has become a major challenge in clinical practice. This article aims to provide an in-depth analysis of the mechanism of action of the HGF/c-Met pathway in OSCC and its interaction with other pathways, and to review the current research status of existing therapeutic drugs. The aim is to provide an important theoretical basis for developing more effective combined treatment strategies and achieving individualized precise treatment, ultimately improving the clinical prognosis and quality of life of patients.

The development of 5G remote robot-assisted gastrointestinal surgery is an important breakthrough in remote surgery in the field of four-level surgery. This paper will review the development history of 5G remote robot assisted gastrointestinal surgery, and share the Gansu province people′s hospital in 5G remote robot assisted gastrointestinal surgery about preoperative preparation, network and equipment connection,“3+2” Trocar layout, safety emergency treatment mechanism of exploratory experience, for 5G remote robot assisted gastrointestinal surgery, and the status and prospect of 5G remote robot assisted gastrointestinal surgery.

Objective:To compare the efficacies of endovascular therapy (EVT) and standard medical therapy in acute ischemic stroke (AIS) patients aged ≥85 years, and analyze the independent influencing factors for poor prognosis of AIS patients after EVT.Methods:Sixty-nine AIS patients aged ≥85 years admitted to Department of Neurology, Xi'an Third Hospital from January 2018 to April 2024, including 40 accepted EVT and 28 accepted standard medicinal therapy, were enrolled. Modified Rankin scale (mRS) was used to evaluate the prognosis of the patients 90 days after onset. General data, prognosis and complications between the EVT group and standard medical therapy group were compared. General data, treatment processes and complications between patients with good prognosis and poor prognosis in the EVT group were compared. Multivariate Logistic regression was used to analyze the independent influencing factors for poor prognosis in AIS patients after EVT.Results:Compared with the standard medical therapy, the EVT group had significantly lower NIHSS score at discharge, greater improvement in NIHSS score (NIHSS score at admission-NIHSS score at discharge), lower mRS score 90 days after onset, higher good prognosis rate, lower mortality rate within 90 days of onset, and longer hospital stay ( P<0.05). In the EVT group, 11 patients (27.5%) had good prognosis and 29 patients (72.5%) had poor prognosis 90 days after onset. Compared with the good prognosis group, the poor prognosis group had significantly higher blood glucose level and lower Alberta Stroke Program Early CT Score (ASPECT) on admission ( P<0.05). Multivariate Logistic regression analysis showed that blood glucose on admission ( OR=2.363, 95% CI: 1.134-4.928, P=0.022) and ASPECT score on admission ( OR=0.273, 95% CI: 0.088-0.854, P=0.026) were independent influencing factors for poor prognosis in AIS patients after EVT. Conclusion:AIS patients aged ≥85 years received EVT have better prognosis compared with those accepted standard medical therapy; these patients with high glucose level and low ASPECT score on admission have poor prognosis.

Objective:To investigate immunotherapy effects and mechanism of BCG and recombinant BCG(rBCG)with c-di-AMP as adjuvant on melanoma in mice model.Methods:Melanoma mice model was established by B16F10 cell subcutaneous injec-tion in groin,and treated with 1×106 CFU of BCG and rBCG by adjacent injection of subcutaneous tumor for 3 times,respectively.Survival of melanotic mice,tumor growth and metastasis were observed.Tumor tissues of mice were isolated to prepare cell suspen-sion,and proportion of immune cells were detected by flow cytometry.Transcriptional levels of immune-related genes in tumor tissues were detected by qRT-PCR.Results:Both BCG and rBCG immunotherapy could significantly inhibit growth in melanoma mice and prolong survival time of mice.rBCG showed better inhibition on metastasis than BCG.Both strains significantly reduced proportion of M2-type macrophages and myeloid-derived suppressor cell associated with tumor growth and metastasis.Both two strains promoted infiltration of lymphocytes in tumor tissues,and rBCG significantly increased proportion of B cells in tumor.BCG immunotherapy upregulated transcription levels of metastasis-related cytokines,while rBCG therapy had no effects on transcriptions of these genes.Conclusion:Both BCG and rBCG have immunotherapeutic effects on melanotic mice,and rBCG with c-di-AMP as adjuvant shows better inhibition on tumor metastasis than BCG,which mechanism was related to regulation of immune response in tumor tissues.

Objective:To compare the efficacies of endovascular therapy (EVT) and standard medical therapy in acute ischemic stroke (AIS) patients aged ≥85 years, and analyze the independent influencing factors for poor prognosis of AIS patients after EVT.Methods:Sixty-nine AIS patients aged ≥85 years admitted to Department of Neurology, Xi'an Third Hospital from January 2018 to April 2024, including 40 accepted EVT and 28 accepted standard medicinal therapy, were enrolled. Modified Rankin scale (mRS) was used to evaluate the prognosis of the patients 90 days after onset. General data, prognosis and complications between the EVT group and standard medical therapy group were compared. General data, treatment processes and complications between patients with good prognosis and poor prognosis in the EVT group were compared. Multivariate Logistic regression was used to analyze the independent influencing factors for poor prognosis in AIS patients after EVT.Results:Compared with the standard medical therapy, the EVT group had significantly lower NIHSS score at discharge, greater improvement in NIHSS score (NIHSS score at admission-NIHSS score at discharge), lower mRS score 90 days after onset, higher good prognosis rate, lower mortality rate within 90 days of onset, and longer hospital stay ( P<0.05). In the EVT group, 11 patients (27.5%) had good prognosis and 29 patients (72.5%) had poor prognosis 90 days after onset. Compared with the good prognosis group, the poor prognosis group had significantly higher blood glucose level and lower Alberta Stroke Program Early CT Score (ASPECT) on admission ( P<0.05). Multivariate Logistic regression analysis showed that blood glucose on admission ( OR=2.363, 95% CI: 1.134-4.928, P=0.022) and ASPECT score on admission ( OR=0.273, 95% CI: 0.088-0.854, P=0.026) were independent influencing factors for poor prognosis in AIS patients after EVT. Conclusion:AIS patients aged ≥85 years received EVT have better prognosis compared with those accepted standard medical therapy; these patients with high glucose level and low ASPECT score on admission have poor prognosis.

The development of 5G remote robot-assisted gastrointestinal surgery is an important breakthrough in remote surgery in the field of four-level surgery. This paper will review the development history of 5G remote robot assisted gastrointestinal surgery, and share the Gansu province people′s hospital in 5G remote robot assisted gastrointestinal surgery about preoperative preparation, network and equipment connection,“3+2” Trocar layout, safety emergency treatment mechanism of exploratory experience, for 5G remote robot assisted gastrointestinal surgery, and the status and prospect of 5G remote robot assisted gastrointestinal surgery.

Objective:To explore the impact on the fertility and outcomes of females with squamous intraepithelial lesion (SIL) undergoing in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) and obstetric outcomes after local treatment. Methods:Patients with SIL undergoing IVF/ICSI were set as the SIL group in the Reproductive Center of the Third Affiliated Hospital of Zhengzhou University from January 2016 to December 2020. While, control group was matched using the propensity scoring method in a 1∶3 ratio in accordance with the age, body mass index, and basic follicle-stimulating hormone, antral follicle count and the oocytes retrieval time. Pregnancy outcomes were compared by analyzing the basic conditions of the two groups, the index of the IVF/ICSI cycles, the clinical pregnancy rate and the implantation rate of the fresh cycles, the cumulative pregnancy rate, the cumulative live birth rate, and obstetric outcomes of patients giving live birth after local treatment were also analyzed.Results:The demographic characteristics were of no significant differences between the SIL group and control group (all P>0.05). As for the IVF/ICSI results, no significant differences were observed in the duration of gonadotropins (Gn) used, total dosage of Gn used, No. of oocytes retrieved, normal fertilization rate, No. of available embryos, No. of high-quality embryos, and No. of blastocyst formation between the two groups (all P>0.05). For fresh embryo transfer cycles, the number of transferred embryos was lower, the clinical pregnancy rate and the implantation rate in the SIL group were higher than those in control group, while the differences were not significant (all P>0.05). The differences of time to pregnancy,the cumulative pregnancy rate and the cumulative live birth rate between SIL group and control group were not statistically significant (all P>0.05). There were no statistically significant differences in delivery methods, gestational age, newborn birth weight, and incidence of pregnancy complications between the two groups (all P>0.05). According to local surgical treatment, 79 patients with SIL who achieved live birth were divided into cold knife conization subgroup, loop electrosurgical excisional procedure subgroup, and no-operation subgroup. There were no statistically significant differences in delivery methods, gestational age, newborn birth weight and incidence of pregnancy complications among the three subgroups (all P>0.05). Conclusion:SIL did not affect fertility of patients or assisted pregnancy outcomes of IVF/ICSI, and local surgical treatment does not increase the risk of preterm birth, low birth weight infants.

Objective:To investigate whether there is an association between season, temperature, as well as cumulative sunlight exposure on the day of oocyte retrieval and clinical outcomes of in vitro fertilization (IVF) and fresh embryo transfer. Methods:It was a retrospective cohort study, including patients who underwent IVF in the Reproductive Center of the Third Affiliated Hospital of Zhengzhou University from August 2015 to October 2019. They were divided into four groups according to the oocyte retrieval date. Spring group: the oocyte retrieval date was from March to May. Summer group: the date of oocyte retrieval was from June to August. Autumn group: the date of oocyte retrieval was from September to November. Winter group: the date of oocyte retrieval was from December to February of the next year. The main outcome measures were clinical pregnancy rate and live birth rate. Binary logistic regression was used to explore the factors affecting clinical pregnancy rate and live birth rate.Results:There were no significant differences in the miscarriage rate and the live birth rate among the four groups (all P>0.05). The pairwise comparison between the groups indicated that the clinical pregnancy rate in the winter group [56.9% (816/1 435)] was lower than that in the summer group [61.5% (1 359/2 210), P=0.005]. Taking winter as the reference, the clinical pregnancy rate in summer was higher (a OR=1.25, 95% CI: 1.09-1.44, P=0.002). The clinical pregnancy rate in spring (a OR=1.14, 95% CI: 0.99-1.32, P=0.073) and autumn (a OR=1.09, 95% CI: 0.94-1.26, P=0.254) was not significantly different from winter. Binary logistic regression analysis showed that higher mean temperature was associated with higher clinical pregnancy rate (a OR=1.01, 95% CI: 1.00-1.01, P=0.005). Season, temperature and cumulative sunshine on the day of egg retrieval had no significant effect on the live birth rate. Conclusion:Summer and high temperature are independent and favorable influencing factors of clinical pregnancy rate. However, different seasons, temperatures and cumulative sunshine had no significant effect on live birth rate.

Objective:To explore whether the duration of oral estrogen treatment before progesterone application affects neonatal outcome in single frozen-thawed embryo transfer (FET) with artificial cycles.Methods:It was a retrospective cohort study. Patients who underwent in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI), receiving single frozen blastocyst transfer with artificial cycle and delivering a single live birth in the Reproductive Center of the Third Affiliated Hospital of Zhengzhou University between January 2015 and December 2019 were included. All FET cycles were divided into four groups according to the estrogen treatment duration before progesterone application, ≤12 d ( n=306), 13-15 d ( n=620), 16-18 d ( n=471), and ≥19 d ( n=275). Primary outcome was the incidence of small for gestational age (SGA). Secondary outcomes were the incidence of preterm birth, low birth weight, macrosomia and large for gestational age (LGA). Results:A total of 1 672 single blastocyst transfer cycles were included. The incidence of SGA among the four groups was 7.8% (24/306), 4.8% (30/620), 5.7% (27/471), and 7.6% (21/275), respectively, with no statistically significant difference ( P=0.204). The results of multiple logistic regression analysis showed that the duration of estrogen used before progesterone application did not affect the incidence of SGA in singleton offspring (with ≤12 d as the reference, 13-15 d: a OR=1.37, 95% CI: 0.70-2.70, P=0.361; 16-18 d: a OR=0.74, 95% CI: 0.40-1.36, P=0.336; ≥19 d: a OR=0.81, 95% CI: 0.44-1.49, P=0.501). There were no significant differences in neonatal preterm birth rate ( P=0.204), low birth weight ( P=0.582), incidences of macrosomia ( P=0.201) and LGA infants ( P=0.335) among the four groups. Conclusion:In artificial FET cycle, the duration of oral estrogen treatment before progesterone application does not affect the outcome of singleton offspring after single blastocyst transfer.