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:This study collected a real-world data on survival and efficacy of gemcitabine-containing therapy in advanced breast cancer. Aimed to find the main reasons of affecting the duration of gemcitabine-base therapy in advanced breast cancer patients.Methods:Advanced breast cancer patients who received gemcitabine-base therapy from January 2017 to January 2019 were enrolled(10 hospitals). The clinicopathological data, the number of chemotherapy cycles and the reasons for treatment termination were collected and analyzed. To identify the reasons related with continuous treatment for advanced breast cancer and the factors which affect the survival and efficacy.Results:A total of 224 patients with advanced breast cancer were enrolled in this study, with a median age of 52 years (26-77 years), 55.4%(124/224) was postmenopausal. Luminal type were 83 cases, TNBC were 97 cases, and human epidermal growth factor receptor 2 (HER's-2) overexpression were 44. At the analysis, 224 patients who received the gemcitabine-based regimens were evaluated, included 5 complete reponse (CR), 77 partial response (PR), 112 stable disease (SD) and 27 progressive disease (PD). The objective response rate (ORR) was 36.6%(82/224). Seventy patients had serious adverse diseases, including leukopenia (9), neutrophilia (49), thrombocytopenia (15), and elevated transaminase (2). The median follow-up time was 41 months (26~61 months), and the median PFS was 5.6 months. The reasons of termination treatment were listed: disease progression were 90 patients; personal reasons were 51 patients; adverse drug reactions were 18 patients; completed treatment were 65 patients. It was found that progression-free survival (PFS) was significantly longer in patients receiving >6 cycles than that in patients with ≤6 cycles (8.2 months vs 5.4 months, HR=2.474, 95% CI: 1.730-3.538, P＜0.001). Conclusions:Gemcitabine-based regimen is generally well tolerated in the Chinese population and has relatively ideal clinical efficacy in the real world. The median PFS is significantly prolonged when the number of treatment cycles are appropriately increased.

Objective:This study collected a real-world data on survival and efficacy of gemcitabine-containing therapy in advanced breast cancer. Aimed to find the main reasons of affecting the duration of gemcitabine-base therapy in advanced breast cancer patients.Methods:Advanced breast cancer patients who received gemcitabine-base therapy from January 2017 to January 2019 were enrolled(10 hospitals). The clinicopathological data, the number of chemotherapy cycles and the reasons for treatment termination were collected and analyzed. To identify the reasons related with continuous treatment for advanced breast cancer and the factors which affect the survival and efficacy.Results:A total of 224 patients with advanced breast cancer were enrolled in this study, with a median age of 52 years (26-77 years), 55.4%(124/224) was postmenopausal. Luminal type were 83 cases, TNBC were 97 cases, and human epidermal growth factor receptor 2 (HER's-2) overexpression were 44. At the analysis, 224 patients who received the gemcitabine-based regimens were evaluated, included 5 complete reponse (CR), 77 partial response (PR), 112 stable disease (SD) and 27 progressive disease (PD). The objective response rate (ORR) was 36.6%(82/224). Seventy patients had serious adverse diseases, including leukopenia (9), neutrophilia (49), thrombocytopenia (15), and elevated transaminase (2). The median follow-up time was 41 months (26~61 months), and the median PFS was 5.6 months. The reasons of termination treatment were listed: disease progression were 90 patients; personal reasons were 51 patients; adverse drug reactions were 18 patients; completed treatment were 65 patients. It was found that progression-free survival (PFS) was significantly longer in patients receiving >6 cycles than that in patients with ≤6 cycles (8.2 months vs 5.4 months, HR=2.474, 95% CI: 1.730-3.538, P＜0.001). Conclusions:Gemcitabine-based regimen is generally well tolerated in the Chinese population and has relatively ideal clinical efficacy in the real world. The median PFS is significantly prolonged when the number of treatment cycles are appropriately increased.

Objective To monitor the antifungal resistance of clinical isolates of Candida spp.in the East China region.Methods MALDI-TOF MS or molecular methods were used to re-identify the strains collected from January 2018 to December 2022.Antifungal susceptibility testing was performed using the broth microdilution method.The susceptibility test results were interpreted according to the breakpoints of 2022 Clinical and Laboratory Standards Institute(CLSI)documents M27 M44s-Ed3 and M57s-Ed4.Results A total of 3 026 strains of Candida were collected,65.33％of which were isolated from sterile body sites,mainly from blood(38.86％)and pleural effusion/ascites(10.21％).The predominant species of Candida were Candida albicans(44.51％),followed by Candida parapsilosis complex(19.46％),Candida tropicalis(13.98％),Candida glabrata(10.34％),and other Candida species(0.79％).Candida albicans showed overall high susceptibility rates to the 10 antifungal drugs tested(the lowest rate being 93.62％).Only 2.97％of the strains showed dose-dependent susceptibility(SDD)to fluconazole.Candida parapsilosis complex had a SDD rate of 2.61％and a resistance rate of 9.42％to fluconazole,and susceptibility rates above 90％to other drugs.Candida glabrata had a SDD rate of 92.01％and a resistance rate of 7.99％to fluconazole,resistance rates of 32.27％and 48.24％to posaconazole and voriconazole non-wild-type strains(NWT),respectively,and susceptibility rates above 90％to other drugs.Candida tropicalis had resistance rates of 29.55％and 26.24％to fluconazole and voriconazole,respectively,resistance rates of 76.60％and 21.99％to posaconazole and echinocandins non-wild-type strains(NWT),and a resistance rate of 2.36％to echinocandins.Conclusions The prevalence and species distribution of Candida spp.in the East China region are consistent with previous domestic and international reports.Candida glabrata exhibits certain degree of resistance to fluconazole,while Candida tropicalis demonstrates higher resistance to triazole drugs.Additionally,echinocandins resistance has emerged in Candida albicans,Candida glabrata,Candida tropicalis,and Candida parapsilosis.

Goniotomy (GT) is a safe and effective type of minimally invasive glaucoma surgery (MIGS) extensively utilized in China.It is particularly suited for treating primary open-angle glaucoma and advanced primary angle-closure glaucoma.Although GT is generally safe, hyphema and postoperative intraocular pressure (IOP) spikes remain common complications after GT.Currently, there is no standardized protocol for managing these issues, which can impact clinicians' assessment of surgical outcomes and potentially affect the prognosis.Therefore, it is crucial to establish comprehensive and detailed management protocols for perioperative hyphema and IOP spike following GT.This will guide clinical practitioners in managing complications appropriately and systematically, thereby promoting the further development and refinement of MIGS.To address these concerns, several domestic glaucoma treatment experts along with members of the Glaucoma Society of Ophthalmology, Guangdong Medical Association reviewed existing literature and held recommendation meetings to develop a guideline for managing perioperative hyphema and IOP spikes following GT.It includes defining perioperative hyphema in GT, discussing its high-risk factors and outcomes, exploring methods for prevention prior to surgery and techniques to reduce bleeding during the procedure, and managing postoperative hemorrhage.Additionally, it covers defining IOP spikes after GT, investigates their causes and contributing factors, and outlines management strategies and anticipated outcomes to provide a valuable resource for clinicians.

Objective:To analyze the distribution and genomic characteristics of SARS-CoV-2 variants isolated from imported cases of COVID-19 in Sichuan Province from December 2022 to January 2023.Methods:This study selected 108 nasal and throat swab samples with fluorescence threshold (Ct)≤32 that were collected from imported COVID-19 cases in Sichuan Province from December 2022 to January 2023. Targeted amplification and Illumina NextSeq? 2000 system were used for whole-genome sequencing. Nextclade and Pangolin online platforms were used to determine the virus genotypes and analyze the mutation loci. A phylogenetic tree was constructed using maximum likelihood.Results:A total of 55 SARS-CoV-2 whole genome sequences with coverage of >95% were obtained, and all of the strains were Omicron variants. Compared with the sequence of reference strain Wuhan-Hu-1, the median number of nucleotide mutation sites of 21L, 22B, 22D, 22E, and 22F genotypes were 93, 75, 92, 78, and 92, and the median number of amino acid mutation sites were 68, 53, 68, 69, and 65, respectively. From December 2022 to January 2023, the predominant circulating SARS-CoV-2 variants from imported cases in Sichuan Province were BA.5.2 (10.91%, 6/55), XBB.1.1 (9.10%, 5/55), BF.7.14 (7.23%, 4/55), and BQ.1.1 (7.23%, 4/55).Conclusions:The distribution of SARS-CoV-2 variants can reflect the global epidemic trend to a certain extent. However, it is different from the distribution of local circulating variants in the Chinese mainland. The XXB variants with transmission advantages can be detected in large numbers of inbound travelers before becoming the predominant circulating strains in the Chinese mainland.

For adapting to the change of modern medical model and suiting social demand of high quality dentists, this paper compares the differences of undergraduate education in stomatology between China and Russia by using the method of Bereday comparative education, trying to provide some reference for the reform of Chinese stomatology education. Curriculum arrangement in China is being constantly explored based on the Russian model. In China, courses are divided into basic medicine, clinical medicine and stomatology in three stages, making students relatively passive in learning. And the ratio of practice to lecture is far more higher in Russia than that in China. Thus, it's necessary to optimize structure and balance the distribution of stomatological curriculum in China, improve and popularize learning models such as problem -based learning (PBL) and so on, so as to promote the development of stomatology education of China to a higher level.

Objective:To explore the CT imaging and clinical features of gastritis cystica profunda (GCP) and improve the level of diagnosis.Methods:From June 2015 to August 2019, the clinical and CT imaging data of 9 GCP patients confirmed by pathology in the First Affiliated Hospital of Zhengzhou University were retrospectively collected. These 9 GCP patients included 3 male and 6 female, aged from 44 to 66 years, with an avereage age of (59±7) years. All the 9 patients underwent plain and enhanced abdominal CT scan. The location, shape, size, margin, density, enhancement pattern and enhancement degree of the lesions were analyzed and summarized.Results:The lesions are more common in gastric antrum (3 cases) and gastric fundus (3 cases). CT imaging showed thickening gastric wall thickening in 3 cases, circular ovoid or circular mass shadow protruding into the gastric cavity in 6 cases. Solid components were dominant in 2 cases and cystic components were dominant in 7 cases. In arterial phase, solid components showed significantly enhancement in 6 cases and moderate enhancement in 3 cases, while muscle layer of lesions were characterized by mild enhancement in 5 cases and moderate enhancement in 4 cases. In venous phase, solid components illustrated as significantly enhancement in 6 cases with progressive pattern and moderate enhancement in 3 cases, while the muscle layer of lesions were featured as progressive moderate enhancement in 4 cases and there is no significant enhancement in the rest 5 cases whose enhancement degree were similar to that of normal gastric wall. Additionally, the surface of the cyst covered with intact mucosa in 7 cases and in other 2 cases without complete mucosa.Conclusion:On the basis of accurate localization, CT scan could provide rich information including size, shape, internal structure and state around the lesion, which is of great value for the diagnosis of GCP.

Objective:To understand the diagnostic value of multiplex PCR (RespiFinder?SMART 22 test kits) and respiratory pathogen screening microfluid chip (TaqMan array cards, TAC) in acute respiratory infection (ARI) in children.Methods:A total of 275 respiratory samples were collected from the Chengdu Children′s Specialist Hospital with respiratory symptoms between August 2018 and August 2019. We randomly selected 120 samples from these respiratory samples. Virus nucleic acid detection of 120 samples were performed with the RespiFinder? SMART 22 and TAC, respectively. And then, we compared the advantages and disadvantages of the two different detection methods.Results:One hundred and twenty samples were detected by RespiFinder?SMART22 and TAC, the positive rates were 88.33% and 93.33%, respectively. The mixed infection rate was 26.67% and 35%, respectively. Among the 120 samples, the consistency rate of the two methods was 88.33%, of which the positive concordance was found in106 samples and the negative concordance was in 7 samples. For 7 cases the result were discordant.Conclusions:In this experimental test, multiplex PCR and TAC have a high consistency in the positive samples, both of which have good clinical application value for the detection of respiratory virus.

Objective: To understand the epidemiological characteristics of influenza A(H1N1)pdm09 virus in Sichuan population during the monitoring period of 2018-2019, and to clarify the antigenic variation, the gene characteristics and the matching of current epidemic strains, vaccine strains, representative strains at home and abroad. Methods: A total of 118 strains of influenza A(H1N1)pdm09 virus isolated in Sichuan region influenza network laboratory from April 2018 to March 2019 were selected. The hemagglutination inhibition (HI) assay was conducted for antigen analysis. The HA and NA genes of 16 strains with low-response strains were sequenced. Phylogenetic analysis and amino acid locus variation analysis were applied using BioEdit and MEGA5.0 software. Results: The result of the antigen analysis demonstrated that more than 95% of the A(H1N1) pdm09 influenza viruses detected were similar to the WHO recommended vaccine strain A/Michigan/45/2015. The analysis of HA gene characteristics showed that some low-response strains had amino acid site variation in the Sa, Sb and Cb regions of the HA protein. A total of 15 low-response strains belonged to the 6B.1 branch. And their evolutionary relationship were close to the representative strains A/beijin-xicheng/SWL1633/2018 and A/brisbane/02/2018, which were popular at home and abroad. Compared with A/sichuan/1/2009, there are mutations involving 6, 14 and 1 amino acid sites in the antigen-determining regions (Sa, Sb, Ca and Cb), non-determined regions and receptor binding site(RBS) respectively. No amino acid site mutations related to resistance to NA gene were found. Conclusions In 2018-2019, the epidemic A(H1N1) pdm09 influenza virus in Sichuan is consistent with the global epidemic characteristics, which also matched with vaccine strains recommended by WHO in the northern hemisphere. Compared with A/sichuan/1/2009 which was the first isolated in China in 2009, there were amino acid sites mutations in antigen-determining region and receptor binding site of the HA protein, and the transmembrane region of the NA protein, drug and antibody binding sites.