Background and purpose:For patients with human epidermal growth factor receptor 2(HER2)-positive metastatic breast cancer,trastuzumab treatment can prolong the overall survival and significantly improve the prognosis of patients.However,the reference original research trastuzumab(Herceptin?)is more expensive.Biosimilars have comparable efficacy and safety profiles while increasing patient access to treatment.This clinical trial aimed to evaluate the efficacy,pharmacokinetics,safety and immunogenicity of the trastuzumab biosimilar AK-HER2 compared to trastuzumab(Herceptin?)in patients with HER2-positive metastatic breast cancer.Methods:This multi-center,randomised,double-blind phase Ⅲ clinical trial was conducted in 43 subcenters in China.This study complied with the research protocol,the ethical principles stated in the Declaration of Helsinki and the quality management standards for drug clinical trials.It was approved by the hospital's medical ethics committee.The clinical trial registration agency is the State Food and Drug Administration(clinical trial approval number:2015L04224;clinical trial registration number:CTR20170516).Written informed consent was obtained from subjects before enrollment.Enrolled patients were randomly assigned to the AK-HER2 group and the control group,respectively receiving AK-HER2 or trastuzumab(initial loading dose 8 mg/kg,maintenance dose 6 mg/kg,every 3 weeks as a treatment cycle,total treatment time is 16 cycles)in combination with docetaxel(75 mg/m2,treatment duration is at least 9 cycles).The primary endpoint of this clinical trial was the objective response rate(ORR9)between the AK-HER2 group and the control group in the 9th cycle.Secondary efficacy endpoints included ORR16,disease control rate(DCR),clinical benefit rate(CBR),progression-free survival(PFS)and 1-year survival rate.In this study,100 subjects(AK-HER2 group to control group=1:1)were randomly selected for blood sample collection after the 6th cycle of medication,The collection time points were 45 minutes after infusion(the end of administration),4,8,24,72,120,168,336,and 504 hours after the end of administration.After collection,blood samples were analyzed by PK parameter set(PKPS).Other evaluation parameters included safety and immunogenicity assessment.Results:A total of 550 patients with HER2-positive metastatic breast cancer were enrolled in this clinical trial between Sep.2017 and Mar.2021.In the AK-HER2 group(n=237),129 subjects in the experimental group achieved complete response(CR)or partial response(PR),and the ORR9 was 54.4%.There were 134 subjects in the control group(n=241)who achieved CR or PR,and the ORR9 was 55.6%.The ORR9 ratio between the AK-HER2 group and the control group was 97.9%[90%confidence interval(CI):85.4%-112.2%,P=0.784],which was not statistically significant.In all secondary efficacy endpoints,no statistically significant differences were observed between the two groups.We conducted a mean ratio analysis of pharmacokinetics(PK)parameters between the AK-HER2 group and the control group,and the results suggested that the pharmacokinetic characteristics of the two drugs are similar.The incidence of treatment emergent adverse event(TEAE)leading to drug reduction or suspension during trastuzumab treatment was 3.6%(10 cases)in the AK-HER2 group and 8.1%(22 cases)in the control group.There was statistically significant difference between the two groups(P=0.027).The incidence rate was significantly lower in the AK-HER2 group than in the control group,and there was no statistically significant difference among the other groups.The differences in the positive rates of anti-drug antibodies(ADA)and neutralizing antibodies(NAB)between groups were of no statistical significance(P=0.385 and P=0.752).Conclusion:In patients with HER2-positive metastatic breast cancer,AK-HER2 was comparable to the trastuzumab(Herceptin?)in terms of drug efficacy,pharmacokinetics,safety and immunogenicity.

Objective To investigate the influence of peripheral blood neutrophil-to-lymphocyte ratio (NLR),monocyte-to-lymphocyte ratio (MLR) and platelet-to-lymphocyte ratio (PLR) on the prognosis in the patients with multiple myeloma (MM).Methods A total of 159 newly diagnosed MM admitted and treated in the Affiliated Hospital of Guizhou Medical University from January 2019 to May 2023 were selected as the study subjects.The general clinical data,blood biochemical and marrow routine detection results before the in-itial treatment were collected.NLR,MLR and PLR were calculated.The univariate and multivariate Cox-re-gression model was adopted to analyze the influencing factors.The receiver operating characteristic (ROC) curve was used to analyze the predictive value.The Kaplan-Meier survival curve and Log-Rank test were used to conduct the survival analysis.Results The ROC curve showed that the critical values of NLR,MLR and PLR were 2.682,0.317 and 147.786 respectively.The patients were divided into the high/low NLR groups (n=61,n=98),high/low MLR group (n=76,n=83) and high/low PLR groups (n=59,n=100).The pro-portions of blood calcium<2.5 mmol/L and creatinine<177 μmmol/L in the low NLR group in the low NLR group were higher compared with the high NLR group (P<0.05);the blood calcium,creatinine and DS stage had statistical differences between the low MLR group and high MLR group (P<0.05);blood calcium had statistical difference between the low PLR group and high PLR group (P<0.05).After 3 treatment courses,the complete remission rate in the high NLR group,high MLR group and high PLR group was significantly lower than that in the corresponding low group (P<0.05).The multivariate Cox-regression analysis results showed that hemoglobin<100 g/L and high PLR were the independent risk factors affecting the progress free survival (PFS) stage in the patients with MM (P<0.05).The age>60 years old was the independent risk factors affecting the overall survival (OS) in the patients with MM (P<0.05).Conclusion NLR,MLR and PLR could serve as the assisted tool to evaluate the prognosis in the patients with MM.

Objective:To evaluate the feasibility and effectiveness of magnetic anchor-guided endoscopic submucosal dissection (MAG-ESD).Methods:A total of 36 patients with gastrointestinal tumors at different sites who underwent MAG-ESD in the First Affiliated Hospital of Xi'an Jiaotong University from March 2020 to October 2022 were enrolled. The anchor success rate, en bloc resection rate, the anchor time, the procedure time, and the complication incidence were observed and analyzed.Results:Among the 36 patients, there were 9 lesions in stomach, 2 in duodenum, 6 in cecum and 19 in colorectum. Thirty-five (97.2%) patients successfully underwent magnetic anchor, and en bloc resection of lesions were completed. No adverse events such as bleeding or perforation occurred. The anchor time and procedure time was 4.0 (2.0-9.5) min and 36 (16-82) min, respectively.Conclusion:MAG-ESD is feasible and effective for gastrointestinal tumors at different sites, with a high anchor success rate and en bloc resection rate, and shorter operation time, especially for difficult submucosal dissection.

【Objective】 To study the role and mechanism of sinomenine in the macrophage polarization induced by gastric cancer cells. 【Methods】 Sinomenine was added to gastric cancer cells BGC-823 and MKN-45， cell viability was measured by CCK-8， cell proliferation was measured by colony formation experiment， Co-culture and Transwell cell migration experiments were used to evaluate the recruitment and polarization of macrophages by sinomenine， flow cytometry was used to evaluate the polarization of macrophages， and qRT-PCR and Western blot were used to detect the expression of gene RNA and protein levels. 【Results】 Sinomenine could inhibit the proliferation of gastric cancer cells and the recruitment of gastric cancer cells to macrophages， thus promoting macrophage M2 polarization. It simultaneously inhibited the expression of STAT6 as well as the expression and phosphorylation of C/EBPβ. When STAT6 is overexpressed， it could reduce these inhibitory effects of sinomenine on gastric cancer cells. Further research found that STAT6 mediated the secretion of IL-6 by gastric cancer cells， which was the cause of sinomenine-mediated macrophage recruitment and M2 polarization. 【Conclusion】 The natural drug sinomenine has a good tumor-suppressing ability against gastric cancer， directly inhibits the survival and migration of gastric cancer cells， and inhibits the expression of IL-6 and the M2 phenotype in the tumor microenvironment， reshapes the tumor environment， and reduces the risk of M2 type macrophages for gastric cancer tumors.

Objective:To evaluate the clinical effect of free anterior lateral thigh flap (ALTF) with cutaneous nerve on repair and reconstruction after radical operation of tongue cancer.Methods:79 patients with tongue cancer who underwent radical resection in the stomatology department of Hunan Provincial People′s Hospital from October 2015 to October 2020 were selected and divided into observation group (38 cases) and control group (41 cases) according to the treatment method. The observation group was reconstructed with free ALTF with cutaneous nerve, and the control group was reconstructed with free ALTF without cutaneous nerve. The survival of the flap was observed and the function and morphology of the reconstructed tongue were evaluated.Results:All flaps survived and had good blood supply; the blood supply was good, the wounds healed in the first stage, and there were no cases of infection and arterial crisis. The appearance of the reconstructed tongue was plump and showed mild atrophy. The observation group was significantly better than the control group in terms of language clarity, masticatory efficiency, sensory excellence rate and University of Washington Quality of Life questionnaire (UW-QOL) score ( P<0.05). Conclusions:The ALTF with cutaneous nerve for repair and reconstruction after radical operation of tongue cancer, can significantly improve the reconstruction of tongue sensory function and the quality of life of patients.

【Objective】 To explore and evaluate infection control measures of preventing cross-contamination of novel coronavirus during gastrointestinal endoscopy treatment. 【Methods】 According to the hospital’s infection control requirements and related documents, infection control measures were formulated and implemented by combining with our actual clinical situation, including the management of the endoscope room, management and protection of patients and endoscopists. Then, we evaluated the effect of these measures. 【Results】 From January 25 to March 10, 2020, a total of 71 patients (53 males and 18 females) completed gastrointestinal endoscopy treatment, with an average age of 54 years (28-81 years). There were 36 (50.7%) cases of emergency treatment. All patients had been kept in quarantine for about 14 days (24±13), and no cross-contamination of novel coronavirus occurred. 【Conclusion】 During the novel coronavirus infection epidemic period, reasonable and effective measures should be taken to minimize the risk of infection in doctors and patients. The endoscope center should strengthen preoperative screening and management of patients, master indications of endoscopic procedures, complete endoscopists’ management and protection work, strictly follow the specifications of sterilizing gastrointestinal endoscopes, and construct the layout of "three zones and two passages".

Objective:To investigate the clinicopathological features, treatment and prognosis of fibrin-associated diffuse large B cell lymphoma (DLBCL) arising within concurrent atrial myxoma.Methods:Six cases of fibrin-associated DLBCL arising within concurrent atrial myxoma diagnosed at the Department of Pathology, Guangdong General Hospital, from 2006 to 2019 were included. The histology, immunophenotype, treatment and prognoses were analyzed.Results:The patients′ age ranged from 46 to 78 years (mean 59 years). There were 3 males and 3 females. The tumors were all discovered incidentally on histological examination of surgical pathology specimens excised for atrial myxoma. All patients appeared to have morphological features of DLBCL, B lineage immunophenotype, high proliferative index and latency type III of Epstein-Barr viral infection. They had complete tumor resections without adjuvant chemotherapy and were healthy at 5- to 120-month follow-ups.Conclusions:Fibrin-associated DLBCL arising within concurrent atrial myxoma is an unusual form of DLBCL associated with chronic inflammation, and its clinical outcome is indolent. The findings suggest that this type of lymphoma does not warrant excessive or unnecessary treatments after complete resection.

Objective: To investigate the clinicopathological features, treatment and prognosis of duodenal-type follicular lymphoma. Methods: Four cases of duodenal-type follicular lymphoma diagnosed at Guangdong General Hospital from 2014 to 2015 with detailed clinical data were included. The histomorphology, immunophenotype, treatment and prognoses were analyzed. Results: The patients′ age ranged from 51 to 57 years (mean 54 years), and there were 2 males and 2 females. The involved sites were gastric fundus in one case, second portion of the duodenum in two cases and terminal ileum in one case. All patients presented with multiple mucosal granules or nodules at endoscopy. Microscopically, there were multiple mucosal neoplastic follicles, constituting grade 1-2 disease based on nodal follicular lymphoma grading system. The tumor cells were positive for CD20, CD10, bcl-6 and bcl-2. CD21 highlighted the follicular dendritic meshwork mainly at the periphery of the follicles. Proliferation index was low. Three patients received rituximab monotherapy for 4 cycles, leading to complete remission. One patient refused therapy and the disease progressed to systemic lymphoma 15 months after the initial diagnosis. Conclusions Duodenal-type follicular lymphoma is a special variant of follicular lymphoma with indolent clinical course. The tumor exhibits morphology of low grade follicular lymphoma with characteristic dendritic meshwork at the periphery of the follicles and a low proliferation index. Prognosis is excellent. Rituximab monotherapy is treatment of choice, but a small minority of patients may progress to systemic disease.

Objective: To investigate MAML2 gene-translocation in primary pulmonary mucoepidermoid carcinoma (PMEC) and pulmanary adenosquamous carcinoma, and the optimal diagnostic immunohistiochemical (IHC) panel in distinguishing PMEC from adenosqumous carcinoma. Methods: Twenty-four cases of PMEC and 44 adenosqumous carcinoma diagnosed in the Guangdong General Hospital were tested for MAML2 translocation by fluorescent in-situ hybridization (FISH) using tissue array. An IHC panel including TTF1, Napsin A, CK5/6, p63, p40 and Ki-67 was performed on the cohort. The clinical data for all cases were collected and all PMEC patients had follow-up information. Results: The patients′ age ranged form 6 to 73 years, with a median age of 32 years. The male to female ratio was 1.4∶1.0. MAML2 translocation was found in 16/24 (66.7%) cases of PMEC whereas all 44 cases adenosqumous carcinoma were negative for translocation. All the cases of the PMEC were negative for TTF1 and Napsin A but positive for CK5/6, p63 and p40 in the intermediate cells and epidermal-like cells. In most PMEC cases, the Ki-67 expression index was lower than 10%. In contrast, most cases of adenosqumous carcinomas expressed TTF1 and Napsin A in the adenomatous component and CK5/6, p63 and p40 in the squamous component, which expression pattern was different from that of PMEC. Based on IHC staining, 2 cases of highly invasive ALK-positive adenocarcinoma mimicing PMEC were also found in the study. Conclusions MAML2 gene translocation can be detected in about two-third of PMEC. Translocation of MAML2 gene and lower morphology grading are associated with good prognosis. The combined use of IHC antibodies panel is helpful to distinguish PMEC from the adenosqumous carcinoma and adenocarcinoma mimicing PMEC.

Objective: To evaluate the feasibility and safety of magnetic tracer technique for preoperative endoscopic marking in laparoscopic surgery. Methods: In the preliminary study, a total of 8 patients with gastric (n=3) or colorectal (n=5) tumors underwent endoscopic magnetic marking before laparoscopic surgery from April to June in 2019. First, a magnet was attached to the lesion by 2 titanium clips under the endoscope. Second, during the subsequent laparoscopic operations, the other magnet was sent to the vicinity of the lesion through the laparoscopic tunnel. The magnet in the abdominal cavity was quickly attracted to the one in the gastrointestinal tract to successfully locate the lesions. Data of preoperative marking and operations of 8 patients were reviewed. Results: All 8 lesions were marked successfully, rapid and accurate intraoperative positioning was achieved. The mean time of endoscopic marking was 5.75±2.45 minutes, and the mean time of intraoperative localization was 1.94±0.56 minutes. All patients underwent laparoscopic tumor resections with accurate localization. The mean proximal and distal resection margins of colorectal tumors were 105 mm and 74 mm respectively. No complications occurred. Conclusion Magnetic tracer technique for laparoscopic localization, simple, safe and accurate for gastrointestinal lesions, can be performed without additional equipment or endoscopic procedures involved.