1.Research status of GLP-1 receptor agonists in the treatment of obesity
Yacong ZHAO ; Chen WANG ; Jianzhong DI
Journal of Chongqing Medical University 2025;50(8):1011-1015
As a chronic and complex disease,obesity can cause many other diseases.Obesity is influenced by many factors.At present,the main treatment methods for obesity are behavioral intervention,medication,endoscopic therapy,and sleeve gastrectomy.New break-throughs and progress have achieved in medication.This article mainly introduces the latest clinical situation and adverse reactions of several representative drugs in glucagon-like peptide-1 receptor agonists,such as liraglutide,semaglutide,and tirzepatide.This article mainly aims to analyze the safety and efficacy of these anti-obesity drugs and provide guidance for future clinical medication.
2.Progress in clinical research on gut microbiota related to obesity
Linwei LI ; Luyao LIU ; Chen WANG ; Jianzhong DI
International Journal of Surgery 2025;52(5):354-360
The gut microbiota plays a crucial role in regulating energy metabolism and obesity progression through mechanisms involving short-chain fatty acid and bile acid metabolism pathways. Obese individuals often exhibit gut microbiota dysbiosis, which can influence lipid metabolism and insulin sensitivity through microbial metabolites and signaling mechanisms. Dietary, pharmaceutical, and bariatric metabolism surgery can modulate the gut microbial, strongly correlating with weight reduction and metabolic benefits. Emerging microbiome-modulating strategies, such as probiotics, prebiotics, synbiotics, and fecal microbiota transplantation, can restore microbial homeostasis and improve bile acid processing, but results differ among people. Moreover, the structural specificity of dietary fibers enables targeted microbial modulation, which provide new perspectives for developing anti-obesity therapies. This review summarizes the mechanisms of interaction between gut microbiota and the host and the clinical research progress in obesity intervention.
3.Construction and identification of a sizeable naive human Fab phage display antibody library
Yakun ZHAO ; Xiaoyue WEI ; Fanliang MENG ; Wentao LIU ; Jiaming FAN ; Lijin LONG ; Wanting WANG ; Jianling CHEN ; Jianzhong ZHANG ; Lihua HE ; Liyong LIU ; Rui ZHAO ; Di SUN ; Xuezhen YUAN ; Xiaomei YAN
Chinese Journal of Epidemiology 2025;46(2):288-295
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.
4.Association of preoperative hepatorenal function and lipid profile with improvement in disordered eating symptoms after bariatric metabolic surgery
Huilin ZHANG ; Ting XU ; Chen WANG ; Hongwei ZHANG ; Jianzhong DI
Chinese Journal of General Surgery 2025;34(4):698-707
Background and Aims:Obesity is often accompanied by symptoms of disordered eating.Although bariatric metabolic surgery can alleviate these symptoms,there are significant individual differences in postoperative outcomes,and effective predictive indicators are lacking.Liver and kidney function,along with lipid profiles,are closely related to metabolic status and may serve as useful markers for preoperative risk stratification and prognosis prediction.This study was conducted to explore the relationship between preoperative metabolic indicators and symptoms of disordered eating,thereby identifying postoperative recovery patterns among obese patients to support individualized management strategies.Methods:A total of 41 obese patients who underwent sleeve gastrectomy at Shanghai Sixth People's Hospital between September 2020 and June 2023 were enrolled,along with 36 healthy volunteers recruited during the same period.Participants completed the Eating Disorder Inventory-2(EDI-2)questionnaire,and serum samples were collected to assess liver function,kidney function,and lipid levels prior to surgery.The Mantel test was used to analyze correlations between metabolic indicators and EDI-2 scores.Latent profile analysis(LPA)was conducted using the indicators significantly correlated with EDI-2 scores to identify subgroups within the obese cohort.Linear mixed models were then applied to examine the trajectories of postoperative symptom changes across subgroups.Results:Levels of cystatin C,cholinesterase,gamma-glutamyl transferase,triglycerides,and apolipoprotein E were significantly higher in the obese group compared to the healthy group(all P<0.05),and EDI-2 total score was also significantly elevated(P<0.05);the prealbumin level in the healthy group was significantly higher than that in the obese group(P<0.05).These six indicators were positively correlated with EDI-2 score(all r>0.20,P<0.05).Based on these markers,the LPA classified the obese group into two subgroups,with subgroup 2 exhibiting higher levels of most metabolic indicators than subgroup 1.During the 18-month postoperative follow-up,both subgroups showed reductions in EDI-2 score,but symptom improvement in subgroup 2 occurred later(month 6)compared to subgroup 1(month 4).Conclusion:Preoperative levels of cholinesterase,gamma-glutamyl transferase,prealbumin,triglycerides,and apolipoprotein E may serve as predictive indicators for improvement in disordered eating symptoms.Recovery patterns after bariatric surgery vary among obese patients with different metabolic profiles,highlighting the need for tailored intervention strategies.
5.Construction and identification of a sizeable naive human Fab phage display antibody library
Yakun ZHAO ; Xiaoyue WEI ; Fanliang MENG ; Wentao LIU ; Jiaming FAN ; Lijin LONG ; Wanting WANG ; Jianling CHEN ; Jianzhong ZHANG ; Lihua HE ; Liyong LIU ; Rui ZHAO ; Di SUN ; Xuezhen YUAN ; Xiaomei YAN
Chinese Journal of Epidemiology 2025;46(2):288-295
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.
6.Exploration of the Implementation Path for the Improvement Goals of National Medical Quality and Safety Based on the Objective and Key Results Method
Ruo JIANG ; Jianzhong DI ; Chengfang HU ; Longjun HU ; Ya YANG ; Jialin YANG ; Songxuan YU ; Mingxiao MA ; Lengchen HOU
Chinese Hospital Management 2025;45(1):70-73
To achieve the national objectives of improving medical quality and safety,the Shanghai Shenkang Hospital Development Center has formulated a list of major targets,tasks,and key results based onthe Objective and Key Results (OKR) method.The primary approaches adopted include establishing an organizational structure to advance medical quality and safety supervision,setting up a series of quantitative indicators for medical quality and safety targets,formulating standardized management systems,building an information platform,and strengthening supervision.It argues that the adoption of OKR can effectively promote the implementation of national target management for improving medical quality and safety,establish a cross-institutional management network for medical quality and safety,strengthen process management,and effectively drive continuous improvement in medical quality and safety.
7.Association of preoperative hepatorenal function and lipid profile with improvement in disordered eating symptoms after bariatric metabolic surgery
Huilin ZHANG ; Ting XU ; Chen WANG ; Hongwei ZHANG ; Jianzhong DI
Chinese Journal of General Surgery 2025;34(4):698-707
Background and Aims:Obesity is often accompanied by symptoms of disordered eating.Although bariatric metabolic surgery can alleviate these symptoms,there are significant individual differences in postoperative outcomes,and effective predictive indicators are lacking.Liver and kidney function,along with lipid profiles,are closely related to metabolic status and may serve as useful markers for preoperative risk stratification and prognosis prediction.This study was conducted to explore the relationship between preoperative metabolic indicators and symptoms of disordered eating,thereby identifying postoperative recovery patterns among obese patients to support individualized management strategies.Methods:A total of 41 obese patients who underwent sleeve gastrectomy at Shanghai Sixth People's Hospital between September 2020 and June 2023 were enrolled,along with 36 healthy volunteers recruited during the same period.Participants completed the Eating Disorder Inventory-2(EDI-2)questionnaire,and serum samples were collected to assess liver function,kidney function,and lipid levels prior to surgery.The Mantel test was used to analyze correlations between metabolic indicators and EDI-2 scores.Latent profile analysis(LPA)was conducted using the indicators significantly correlated with EDI-2 scores to identify subgroups within the obese cohort.Linear mixed models were then applied to examine the trajectories of postoperative symptom changes across subgroups.Results:Levels of cystatin C,cholinesterase,gamma-glutamyl transferase,triglycerides,and apolipoprotein E were significantly higher in the obese group compared to the healthy group(all P<0.05),and EDI-2 total score was also significantly elevated(P<0.05);the prealbumin level in the healthy group was significantly higher than that in the obese group(P<0.05).These six indicators were positively correlated with EDI-2 score(all r>0.20,P<0.05).Based on these markers,the LPA classified the obese group into two subgroups,with subgroup 2 exhibiting higher levels of most metabolic indicators than subgroup 1.During the 18-month postoperative follow-up,both subgroups showed reductions in EDI-2 score,but symptom improvement in subgroup 2 occurred later(month 6)compared to subgroup 1(month 4).Conclusion:Preoperative levels of cholinesterase,gamma-glutamyl transferase,prealbumin,triglycerides,and apolipoprotein E may serve as predictive indicators for improvement in disordered eating symptoms.Recovery patterns after bariatric surgery vary among obese patients with different metabolic profiles,highlighting the need for tailored intervention strategies.
8.Exploration of the Implementation Path for the Improvement Goals of National Medical Quality and Safety Based on the Objective and Key Results Method
Ruo JIANG ; Jianzhong DI ; Chengfang HU ; Longjun HU ; Ya YANG ; Jialin YANG ; Songxuan YU ; Mingxiao MA ; Lengchen HOU
Chinese Hospital Management 2025;45(1):70-73
To achieve the national objectives of improving medical quality and safety,the Shanghai Shenkang Hospital Development Center has formulated a list of major targets,tasks,and key results based onthe Objective and Key Results (OKR) method.The primary approaches adopted include establishing an organizational structure to advance medical quality and safety supervision,setting up a series of quantitative indicators for medical quality and safety targets,formulating standardized management systems,building an information platform,and strengthening supervision.It argues that the adoption of OKR can effectively promote the implementation of national target management for improving medical quality and safety,establish a cross-institutional management network for medical quality and safety,strengthen process management,and effectively drive continuous improvement in medical quality and safety.
9.Cell softness reveals tumorigenic potential via ITGB8/AKT/glycolysis signaling in a mice model of orthotopic bladder cancer
Shi QIU ; Yaqi QIU ; Linghui DENG ; Ling NIE ; Liming GE ; Xiaonan ZHENG ; Di JIN ; Kun JIN ; Xianghong ZHOU ; Xingyang SU ; Boyu CAI ; Jiakun LI ; Xiang TU ; Lina GONG ; Liangren LIU ; Zhenhua LIU ; Yige BAO ; Jianzhong AI ; Tianhai LIN ; Lu YANG ; Qiang WEI
Chinese Medical Journal 2024;137(2):209-221
Background::Bladder cancer, characterized by a high potential of tumor recurrence, has high lifelong monitoring and treatment costs. To date, tumor cells with intrinsic softness have been identified to function as cancer stem cells in several cancer types. Nonetheless, the existence of soft tumor cells in bladder tumors remains elusive. Thus, our study aimed to develop a microbarrier microfluidic chip to efficiently isolate deformable tumor cells from distinct types of bladder cancer cells.Methods::The stiffness of bladder cancer cells was determined by atomic force microscopy (AFM). The modified microfluidic chip was utilized to separate soft cells, and the 3D Matrigel culture system was to maintain the softness of tumor cells. Expression patterns of integrin β8 (ITGB8), protein kinase B (AKT), and mammalian target of rapamycin (mTOR) were determined by Western blotting. Double immunostaining was conducted to examine the interaction between F-actin and tripartite motif containing 59 (TRIM59). The stem-cell-like characteristics of soft cells were explored by colony formation assay and in vivo studies upon xenografted tumor models. Results::Using our newly designed microfluidic approach, we identified a small fraction of soft tumor cells in bladder cancer cells. More importantly, the existence of soft tumor cells was confirmed in clinical human bladder cancer specimens, in which the number of soft tumor cells was associated with tumor relapse. Furthermore, we demonstrated that the biomechanical stimuli arising from 3D Matrigel activated the F-actin/ITGB8/TRIM59/AKT/mTOR/glycolysis pathways to enhance the softness and tumorigenic capacity of tumor cells. Simultaneously, we detected a remarkable up-regulation in ITGB8, TRIM59, and phospho-AKT in clinical bladder recurrent tumors compared with their non-recurrent counterparts.Conclusions::The ITGB8/TRIM59/AKT/mTOR/glycolysis axis plays a crucial role in modulating tumor softness and stemness. Meanwhile, the soft tumor cells become more sensitive to chemotherapy after stiffening, that offers new insights for hampering tumor progression and recurrence.
10.Optimizing management strategies for blood transfusion in the severe trauma patients in the emergency department
Chinese Journal of Emergency Medicine 2024;33(12):1760-1764
Objectives:To conduct an optimizing blood transfusion process for severe trauma patients in the emergency department and investigate its effectiveness.Methods:Based on the current situation and analysis of the reasons for the current blood transfusion preparation practices for severely injured patients, the optimization was carried out in three aspects: the medical treatment process, departmental responsibilities, and the blood transfusion process. The differences in the key time links of emergency blood transfusion were compared between 40 patients with severe trauma treated by traditional protocols (July-August 2022) and 40 patients treated by optimized process (April 2023) and the treatment effects were also investigated. T-tests were used to compare the key time links, and chi-square tests were used to compare the rates of successful resuscitation before and after optimization.Results:(1) Following process optimization, the average emergency department blood transfusion preparation time for severe trauma patients was significantly reduced compared with the traditional process [(28.40 ± 2.72) min vs. (64.83 ± 11.57) min, P<0.01]. (2) Average blood sample submission time decreased from (20.83 ± 7.88) min to (7.80 ± 1.59) min, and average blood retrieval time decreased from (15.08 ± 5.72) min to (8.10 ± 2.30) min, both with P<0.01. (3) Optimized procedures resulted in a reduction of resuscitation room stay time from (410.40 ± 157.69) min to (337.15 ± 74.09) min ( P<0.01). (4) Post-optimization, the Intensive Care Unit (ICU) length of stay for successfully resuscitated patients was significantly shorter [(13.54 ± 4.82) days vs. (16.61 ± 6.08) days, P<0.05]. Conclusions:Through process optimization, the blood transfusion process for severe trauma emergency patients is further standardized, reducing delays at each stage and improving both transfusion and treatment efficiency.

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