Objective To evaluate the efficacy and safety of enteric-coated metformin hydrochloride capsules(Junlida?)in patients with T2DM and poor glycemic control under lifestyle interventions.Methods In this study,419 patients with T2DM were recruited from 15 research centers from July 2020 to March 2022,and randomly divided into observation(Obs)group(n=209)and control group(Con,n=210)using a multicenter,randomized,double-blind,non-inferiority trial design.Patients in the Obs group were treated with enteric-coated Metformin hydrochloride capsules(Junlida?),and patients in the Con group were treated with Metformin hydrochloride tablets(Glucophage?).The optimal effective dose of 2 g/d was achieved within 4 weeks,and the reasonable dose was maintained until the end of treatment.The treatment period was 24 weeks.HbA1c and its compliance rate,FPG,and body weight were compared between the two groups in full analysis set(FAS)and protocol set(PPS).Safety and adverse events(AE)were evaluated in safety set(SS).Results A total of 414 participants were randomized(207 cases in Obs group and 207 cases in Con group).414 cases in FAS population(207 cases in Obs group and 207 cases in Con group),and 328 cases in PPS population(164 cases in Obs group and 164 cases in Con group),and 414 cases in SS population(207 cases in Obs group and 207 cases in Con group).After treatment,HbA1c,FPG and body weight were lower in both groups(P<0.05)in FAS and PPS.HbA1c compliance rate was not significantly different between the two groups in FAS and PPS(P>0.05).The results of non-inferiority test showed that the lower limit was>-0.4%in both FAS(-0.154,95%CI-0.384～0.069)and PPS(-0.139,95%CI-0.390～0.112),and the Obs group reached non-inferiority end point.The achievement rate,compliance rate,safety index and incidence of AE were not significantly different between the two groups(P>0.05).Conclusions Junlida? demonstrated non-inferiority to Glucophage? in glycemic control and can be safely and effectively used in patients with diabetes.

Purpose To investigate the clinicopathological characteristics of the gastric oxyntic gland adenoma(GOGA).Methods We collected 18 samples of GOGA,histopathological features and immunohistochemical staining were assessed.Main features of pathological diagnosis,treatment methods and follow-up were retrospectively analyzed.Results There were 18 patients,including 9 females and 9 males,aged from 36 to 86 years old.The endoscopic im-age showed a flat lesion with whitish in color or a polypoid protrusions.The size ranged from 0.3 cm to 0.8 cm.Hema-toxylin and eosin staining showed irregular glandular structures in the mucosal lamina propria,with branched and anas-tomosed patterns.The tumour demonstrating composed of chief cells hyperplasia with mild nuclear atypia.All lesions were confined to the mucous lamina propria.There was no atrophic within the peripheral gastic mucosa.Immunohisto-chemical examination showed positive for Pepsinogen-Ⅰ and MUC6.Gene mutation were analyzed in 2 cases using next generation sequence technology,and no KRAS and GNAS mutation had been detected.Endoscopic surgical treatment was performed in 11 cases,and biopsy forceps removal was carried out in 7 cases.No recurrence or metastasis was ob-served during the follow-up period of 1 to 58 months.Conclusion GOGA is a rare lesion,and appears to behave bio-logically benign.A full understanding of its histological morphology and biological behavior can improve the diagnostic ability of clinincans,and facilitate further research in the future.

Objective:To evaluate the survival benefit of surgical treatment for intrahepatic cholangiocarcinoma.Methods:This study is conducted based on the hepatobiliary tumor registry database. From May 2009 to December 2022,a total of 704 patients who were initially diagnosed with intrahepatic cholangiocarcinoma and underwent liver resection were consecutively enrolled at the Hepatobiliary Center of the First Affiliated Hospital of Nanjing Medical University. Among them,there were 380 males and 324 females,aged ( M(IQR)) 61(15) years(range:27 to 88 years). Twenty-six (3.7%) patients received neoadjuvant therapy before surgery. The overall survival(OS) and disease-free survival(DFS) rates were estimated by life table method, and Kaplan-Meier survival curves were plotted. Log-rank test was used to compare the survival difference among tumor-node-metastasis(TNM) staging or three periods. The OS and DFS differences among lymph node groups or adjuvant treatment groups were quantified as HR with 95% CI estimated using Cox proportional-hazards model with adjustment for prognostic factors. Results:Among the 704 patients,349 cases(49.6%) underwent major hepatectomy (≥3 segments),331(47.0%) had lymph node resection during surgery,and 524 cases(74.4%) achieved R0 resection. The morbidity of Clavien-Dindo grade Ⅲ or higher complications was 16.5%(116/704),with a mortality rate of 3.0%(21/704) within 30 days post-surgery. The median OS time was 27.1 months, and the OS rates at 1-,3-,5- and 10-year were 69.1%, 42.4%,34.1% and 24.5%,respectively. The median DFS time was 10.5 months,and the corresponding DFS rates were 46.0%,25.4%,21.9% and 16.9%,respectively. According to the 8 th edition of AJCC staging system, the 5-year survival rates for ⅠA,ⅠB,Ⅱ,ⅢA,ⅢB and Ⅳ were 68.4%, 43.2%, 30.3%,32.2%,14.0% and 0,respectively. The corresponding DFS rates were 55.8%, 28.1%,13.8%,21.2%,3.3% and 0,respectively. There were no statistically significant differences of OS or DFS between stage ⅠB and Ⅱ, stage ⅠB and ⅢA, or between stage Ⅱ and ⅢA(Log-rank test:all P>0.05),while there were significant differences of OS and DFS among other stages(Log-rank test:all P<0.05). Using Cox model with adjustment for prognostic factors, there were no statistically significant differences of OS and DFS between non-lymphadenectomy group or the biopsy-N0 group and dissection-N0 group(both P>0.05). However,the overall and disease-free survival of the biopsy-N1 group or dissection-N1 group were worse than those of dissection-N0 group(both P<0.05),with overall survival being better in dissection-N1 group than biopsy-N1 group( P=0.017). Overall survival in the period from 2019 to 2022 were significantly superior to that during the periods from 2009 to 2013 and 2014 to 2018(both P<0.01). Adjusting for prognostic factors, the disease-free and overall survival of the postoperative adjuvant therapy group were significantly better than those of the observation group in the period 2019 to 2022(both P<0.01). Conclusions:Surgery remains a milestone for achieving long-term survival for patients with intrahepatic cholangiocarcinoma. Regional lymph node dissection is required for patients with lymph node metastasis. Adjuvant therapy can significantly reduce tumor recurrence and prolong overall survival.

The standardized implementation of intraoperative nerve monitoring technology significantly minimizes surgical injury risks. Its application in endoscopic and robotic thyroid surgeries enhances procedural safety. Building upon standardized protocols, our team has innovated technical extensions through accumulated clinical experience, systematically formulated as operational guidelines. This article elucidated these technical extensions through pictures and videos, aiming to improve the safety and procedural fluency of endoscopic and robotic thyroidectomies.

Objective To investigate the safety and efficacy of mechanical thrombectomy combined with umbilical cord blood mononuclear cell microtransplantation in the treatment of patients with acute ischemic stroke due to large vessel occlusion. Methods A prospective study was conducted among 61 patients with acute ischemic stroke due to large vessel occlusion in the anterior intracranial circulation who underwent mechanical thrombectomy in our hospital from February 2021 to February 2023， and they were randomly divided into experimental group and control group. The patients in the experimental group underwent mechanical thrombectomy combined with umbilical cord blood mononuclear cell microtransplantation， while those in the control group underwent mechanical thrombectomy alone， and there was no difference in conventional drug treatment between the two groups. The Mann-Whitney U test， chi-square test， and logistic regression analysis were used， with P<0.05 indicating statistical significance. Results There were no significant abnormalities in blood tests and imaging findings in either group at 90 days and 6 months after treatment. There was no significant difference in the degree of neurological deficit （NIHSS score） between the two groups before surgery and on days 1，3，7， and 30 after surgery （P>0.05）. The experimental group had a higher overall response rate （the proportion of patients with an mRS score of ≤2 on day 90 after surgery） than the control group [41.4% （12/29） vs 32.2% （10/31）， P>0.05]. There was no significant difference in limb motor function [Fugl-Meyer Assessment （FMA） score] between the two groups before surgery（P>0.05）， and the experimental group had a better FMA score than the control group on day 90 after surgery（P<0.05）. Conclusion Mechanical thrombectomy combined with umbilical cord blood mononuclear cell microtransplantation can effectively improve the long-term functional prognosis of patients， with a favorable safety profile.

Objective To investigate the potential risk factors for hemorrhagic transformation（HT）after mechanical thrombectomy（MT）in patients with acute ischemic stroke due to anterior circulation large vessel occlusion（AIS-AC-LVO），and to provide a scientific evidence for reducing post-thrombectomy HT and improving the prognosis of patients. Methods retrospective analysis was performed for the data of 605 patients with AIS-AC-LVO. The Logistic regression analysis was performed for related clinical data to identify independent predictive factors for HT after MT，with a significance threshold of P<0.05. Results A total of 605 patients were included in this study，among whom 207（34.2%）developed HT after MT，while 398（65.8%）did not experience HT. The statistical analysis showed that multiple attempts of thrombectomy（OR=1.340，P=0.003），a prolonged time of operation（OR=1.005，P=0.024），a low ASPECTS score before surgery（OR=0.798，P<0.001），postoperative mTICI≤2a（OR=6.329，P=0.032），a low platelet count before surgery（OR=0.995，P=0.008），and a high level of blood glucose before surgery（OR=1.088，P=0.009）were independent predictive factors for HT. Symptomatic intracranial hemorrhage（sICH）was observed in 68 patients（11.2%），and a history of atrial fibrillation（OR=3.151，P=0.003），a low ASPECTS score before surgery（OR=0.868，P=0.007），a prolonged time of operation（OR=1.009，P<0.001），poor collateral circulation（ASITN/SIR<2）（OR=2.307，P=0.035），a low platelet count before surgery（OR=0.993，P=0.012），a high level of D-dimer before surgery（OR=1.050，P=0.012），and a high level of blood glucose before surgery（OR=1.138，P=0.013）were independent predictive factors for sICH. Conclusion Multiple attempts of thrombectomy，a prolonged time of operation，a low ASPECTS score before surgery，postoperative mTICI≤2a，a low platelet count before surgery，and a high level of blood glucose before surgery are independent predictive factors for HT. A history of atrial fibrillation，a low ASPECTS score before surgery，a prolonged time of operation，poor collateral circulation（ASITN/SIR<2），a low platelet count before surgery，a high level of D-dimer before surgery，and a high level of blood glucose before surgery are independent predictive factors for sICH. Identifying such risk factors is crucial for reducing HT after MT and improving the efficacy of thrombectomy.

Objective:To construct a sizeable naive human Fab phage display antibody library to screen high-affinity specific antibodies in vitro. Methods:Total RNA was extracted from peripheral blood mononuclear cells (PBMCs) of 126 healthy individuals, subsequently reverse-transcribed into cDNA, and used as a template. PCR amplification was performed to obtain the V H from IgG, IgM and light chain κ, λ, separately, with the initial PCR products serving as templates for a second round of PCR. Overlap extension PCR was employed to generate fragments of the κ and λ light chains. These fragments were ligated with the phage vector pNC3, which harbors the variable region 1 of the heavy chain, to construct a recombinant phage plasmid. This plasmid was then electroporated into competent Escherichia Coli TG1 cells to establish a naive human Fab phage display antibody library. One hundred clones were randomly selected for identification and sequencing, and antibody gene polymorphisms were analyzed using the IMGT database and MAFFT software. Recombinant α-hemolysin from Staphylococcus aureus was utilized to screen Fab antibody fragments through biopanning of the antibody library, followed by random selection of phage ELISA-identified clones. The positive clones (antigen A450∶blank control A450≥2.1) were sequenced. Results:Two large naive Fab phage display antibody libraries were successfully constructed, in which the capacity of κ and λ chain antibody libraries were 1.25×10 11 and 1.54×10 11, respectively. The titers for two antibody libraries were 6.04×10 13 CFU/ml and 3.50×10 13 CFU/ml. The positive transformation insertion rates for κ and λ chain antibody libraries were 96% (96/100) and 100% (100/100), respectively. Sequence analysis revealed that all antibody sequences were unique. The amino acid sequences in the skeletal region were relatively conserved. In contrast, significant variations in the length of the complementarity determining region (CDR) were found, and the diversity of amino acid sequence of the complementary determining region was high, especially the CDR3. Analysis using the IMGT database indicated that the sequences exhibited a broad distribution across variable-diversity-joining gene families. After six rounds of panning, specific phage antibodies enrichment targeting α-hemolysin were achieved. A total of 142 monoclonal antibodies were sequenced, yielding 8 distinct Fab antibody sequences. Conclusion:This study successfully constructed two naive human Fab phage display antibody libraries with large capacity and good diversity, which can be used for screening human antibodies for serum epidemiology.

Objective:To construct a sizeable naive human Fab phage display antibody library to screen high-affinity specific antibodies in vitro. Methods:Total RNA was extracted from peripheral blood mononuclear cells (PBMCs) of 126 healthy individuals, subsequently reverse-transcribed into cDNA, and used as a template. PCR amplification was performed to obtain the V H from IgG, IgM and light chain κ, λ, separately, with the initial PCR products serving as templates for a second round of PCR. Overlap extension PCR was employed to generate fragments of the κ and λ light chains. These fragments were ligated with the phage vector pNC3, which harbors the variable region 1 of the heavy chain, to construct a recombinant phage plasmid. This plasmid was then electroporated into competent Escherichia Coli TG1 cells to establish a naive human Fab phage display antibody library. One hundred clones were randomly selected for identification and sequencing, and antibody gene polymorphisms were analyzed using the IMGT database and MAFFT software. Recombinant α-hemolysin from Staphylococcus aureus was utilized to screen Fab antibody fragments through biopanning of the antibody library, followed by random selection of phage ELISA-identified clones. The positive clones (antigen A450∶blank control A450≥2.1) were sequenced. Results:Two large naive Fab phage display antibody libraries were successfully constructed, in which the capacity of κ and λ chain antibody libraries were 1.25×10 11 and 1.54×10 11, respectively. The titers for two antibody libraries were 6.04×10 13 CFU/ml and 3.50×10 13 CFU/ml. The positive transformation insertion rates for κ and λ chain antibody libraries were 96% (96/100) and 100% (100/100), respectively. Sequence analysis revealed that all antibody sequences were unique. The amino acid sequences in the skeletal region were relatively conserved. In contrast, significant variations in the length of the complementarity determining region (CDR) were found, and the diversity of amino acid sequence of the complementary determining region was high, especially the CDR3. Analysis using the IMGT database indicated that the sequences exhibited a broad distribution across variable-diversity-joining gene families. After six rounds of panning, specific phage antibodies enrichment targeting α-hemolysin were achieved. A total of 142 monoclonal antibodies were sequenced, yielding 8 distinct Fab antibody sequences. Conclusion:This study successfully constructed two naive human Fab phage display antibody libraries with large capacity and good diversity, which can be used for screening human antibodies for serum epidemiology.

Objective To evaluate the efficacy and safety of enteric-coated metformin hydrochloride capsules(Junlida?)in patients with T2DM and poor glycemic control under lifestyle interventions.Methods In this study,419 patients with T2DM were recruited from 15 research centers from July 2020 to March 2022,and randomly divided into observation(Obs)group(n=209)and control group(Con,n=210)using a multicenter,randomized,double-blind,non-inferiority trial design.Patients in the Obs group were treated with enteric-coated Metformin hydrochloride capsules(Junlida?),and patients in the Con group were treated with Metformin hydrochloride tablets(Glucophage?).The optimal effective dose of 2 g/d was achieved within 4 weeks,and the reasonable dose was maintained until the end of treatment.The treatment period was 24 weeks.HbA1c and its compliance rate,FPG,and body weight were compared between the two groups in full analysis set(FAS)and protocol set(PPS).Safety and adverse events(AE)were evaluated in safety set(SS).Results A total of 414 participants were randomized(207 cases in Obs group and 207 cases in Con group).414 cases in FAS population(207 cases in Obs group and 207 cases in Con group),and 328 cases in PPS population(164 cases in Obs group and 164 cases in Con group),and 414 cases in SS population(207 cases in Obs group and 207 cases in Con group).After treatment,HbA1c,FPG and body weight were lower in both groups(P<0.05)in FAS and PPS.HbA1c compliance rate was not significantly different between the two groups in FAS and PPS(P>0.05).The results of non-inferiority test showed that the lower limit was>-0.4%in both FAS(-0.154,95%CI-0.384～0.069)and PPS(-0.139,95%CI-0.390～0.112),and the Obs group reached non-inferiority end point.The achievement rate,compliance rate,safety index and incidence of AE were not significantly different between the two groups(P>0.05).Conclusions Junlida? demonstrated non-inferiority to Glucophage? in glycemic control and can be safely and effectively used in patients with diabetes.

Purpose To investigate the clinicopathological characteristics of the gastric oxyntic gland adenoma(GOGA).Methods We collected 18 samples of GOGA,histopathological features and immunohistochemical staining were assessed.Main features of pathological diagnosis,treatment methods and follow-up were retrospectively analyzed.Results There were 18 patients,including 9 females and 9 males,aged from 36 to 86 years old.The endoscopic im-age showed a flat lesion with whitish in color or a polypoid protrusions.The size ranged from 0.3 cm to 0.8 cm.Hema-toxylin and eosin staining showed irregular glandular structures in the mucosal lamina propria,with branched and anas-tomosed patterns.The tumour demonstrating composed of chief cells hyperplasia with mild nuclear atypia.All lesions were confined to the mucous lamina propria.There was no atrophic within the peripheral gastic mucosa.Immunohisto-chemical examination showed positive for Pepsinogen-Ⅰ and MUC6.Gene mutation were analyzed in 2 cases using next generation sequence technology,and no KRAS and GNAS mutation had been detected.Endoscopic surgical treatment was performed in 11 cases,and biopsy forceps removal was carried out in 7 cases.No recurrence or metastasis was ob-served during the follow-up period of 1 to 58 months.Conclusion GOGA is a rare lesion,and appears to behave bio-logically benign.A full understanding of its histological morphology and biological behavior can improve the diagnostic ability of clinincans,and facilitate further research in the future.