1.Consensus and controversies in the clinical application of translational therapy for liver cancer
Chinese Journal of General Surgery 2025;34(1):47-53
Translational therapy for liver cancer,as an emerging treatment strategy,is driving advancements in the management of intermediate and advanced liver cancer.Through continuous exploration by experts nationwide,translational therapy for liver cancer has reached a consensus,providing valuable scientific guidance for clinical practice.However,as treatment methods continue to evolve,translational therapy still faces numerous urgent challenges,particularly in areas such as personalized treatment,efficacy evaluation,and combined therapeutic strategies.These issues have become contentious and hotly debated topics,creating a situation where"consensus and controversy coexist,and opportunities and challenges intersect."To address these challenges,experts in the field of liver cancer must strengthen collaboration and communication,promote high-quality basic and clinical research,and continuously refine treatment protocols in practice,ultimately offering patients more scientific and precise therapeutic options.
2.Consensus and controversies in the clinical application of translational therapy for liver cancer
Chinese Journal of General Surgery 2025;34(1):47-53
Translational therapy for liver cancer,as an emerging treatment strategy,is driving advancements in the management of intermediate and advanced liver cancer.Through continuous exploration by experts nationwide,translational therapy for liver cancer has reached a consensus,providing valuable scientific guidance for clinical practice.However,as treatment methods continue to evolve,translational therapy still faces numerous urgent challenges,particularly in areas such as personalized treatment,efficacy evaluation,and combined therapeutic strategies.These issues have become contentious and hotly debated topics,creating a situation where"consensus and controversy coexist,and opportunities and challenges intersect."To address these challenges,experts in the field of liver cancer must strengthen collaboration and communication,promote high-quality basic and clinical research,and continuously refine treatment protocols in practice,ultimately offering patients more scientific and precise therapeutic options.
3.Influencing of preoperative biliary drainage on surgery-related complications after pancreatico-duodenectomy
Huajun LIN ; Zhewen FENG ; Chenglin XIN ; Chengjian GUAN ; Xiaodong ZHANG ; Yiyang MIN ; Xiaozhe GU ; Wei GUO ; Dong WANG
Chinese Journal of Digestive Surgery 2023;22(7):909-915
Objective:To investigate the influencing of preoperative biliary drainage on surgery-related complications after pancreaticoduodenectomy.Methods:The retrospective case-control study was conducted. The clinical data of 267 patients with periampullary space-occupying lesion who were admitted to Beijing Friendship Hospital of Capital Medical University from January 2016 to July 2020 were collected. There were 166 males and 101 females, aged 61 (range, 54?84)years. Observation indicators: (1) comparison of preoperative situations in patients with and without preoperative biliary drainage; (2) comparison of intraoperative and postoperative situations in patients with and without preoperative biliary drainage; (3) methods and efficacy of preoperative biliary drainage; (4) factors influencing surgery-related complications after pancreaticoduodenec-tomy. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the t test. Measurement data with skewed distribution were represented as M(rang) or M( Q1, Q3), and comparison between groups was conducted using the Mann-Whitney U test. Count data were described as absolute numbers or percentages, and comparison between groups was conducted using the chi-square test. Univariate analysis was conducted using the corresponding statistical methods based on data type. Multivariate analysis was conducted using the Logistic stepwise regression model. Results:(1) Comparison of preoperative situations in patients with and without preoperative biliary drainage. Of the 267 patients, there were 104 cases with preoperative biliary drainage and 163 cases without preoperative biliary drainage. Cases with malignant tumor, cases with borderline tumor, cases with chronic pancreatitis were 89, 13, 2 in patients with preoperative biliary drainage, versus 111, 41, 11 in patients without preoperative biliary drainage, showing significant differences in pathology type between them ( χ2=10.652, P<0.05). (2) Comparison of intraoperative and postoperative situations in patients with and without preoperative biliary drainage. There was no significant difference in operation time, volume of intra-operative blood loss, postoperative complications, grade B pancreatic fistula, grade C pancreatic fistula, biliary leakage, abdominal or gastrointestinal bleeding, incidence of abdominal infection, white blood cell count at postoperative day 1, white blood cell count at postoperative day 3, neutrophil-to-lymphocyte ratio at postoperative day 1, neutrophil-to-lymphocyte ratio at postoperative day 3, C-reactive protein-albumin ratio at postoperative day 1, C-reactive protein-albumin ratio at post-operative day 3, duration of hospital stay between the 104 patients with preoperative biliary drainage and the 163 patients without preoperative biliary drainage ( P>0.05). (3) Methods and efficacy of preoperative biliary drainage. Of the 104 patients with preoperative biliary drainage, there were 40 cases receiving endoscopic nasobiliary drainage with drainage time as (12±2)days, there were 38 cases receiving percutaneous transhepatic cholangial drainage with drainage time as (7±1)days, and there were 26 cases receiving endoscopic retrograde biliary drainage with drainage time as (19±2)days. The total bilirubin, direct bilirubin, aspartate transaminase, alanine aminotrans-ferase in 104 patients were (223±18)μmol/L, (134±11)μmol/L, (112±10)U/L, (160±16)U/L before biliary drainage and (144±13)μmol/L, (84±8)μmol/L, (79±8)U/L, (109±12)U/L after biliary drainage, showing significant differences in the above indicators ( t=3.544, 3.608, 2.523, 2.509, P<0.05). (4) Factors influencing surgery-related complications after pancreatocoduodenectomy. Results of multi-variate analysis showed that operation time was an independent factor influencing surgery-related complications after pancreaticoduodenectomy ( odds ratio=1.005, 95% confidence interval as 1.002?1.008, P<0.05). Conclusions:Preoperative biliary drainage does not increase the incidence of complications related to pancreaticoduodenectomy in patients with periampullary space-occupying lesion. Operation time is an independent factor influencing postoperative surgery-related complications.
4.Correlation of the duration of preoperative biliary drainage and postoperative complications after pancreaticoduodenectomy
Huajun LIN ; Zhewen FENG ; Chengjian GUAN ; Xiaodong ZHANG ; Chenglin XIN ; Xiaozhe GU ; Yiyang MIN ; Dong WANG ; Wei GUO
Cancer Research and Clinic 2023;35(5):321-327
Objective:To investigate the effect of the duration of preoperative biliary drainage on postoperative complications after pancreaticoduodenectomy.Methods:The clinical data of 102 patients with benign and malignant hepatopancreatic ductal periampullary tumors who underwent pancreaticoduodenectomy and preoperative biliary drainage in Beijing Friendship Hospital, Capital Medical University from January 2016 to July 2020 were retrospectively analyzed. According to the median duration of preoperative biliary drainage, the patients were divided into short-term drainage group (≤ the median duration of biliary drainage) and long-term drainage group (> the median duration of biliary drainage). The general data, the effect of biliary drainage, inflammation-related indicators and postoperative complications were compared between the two groups. Multivariate logistic regression was used to screen the risk factors related to the postoperative severe complications.Results:Of the 102 patients, 68 (66.7%) were males and 34 (33.3%) were females, with a median age of 63 years (43-80 years). The median duration of preoperative biliary drainage was 14 d. There were 68 patients in short-term drainage group and 34 patients in long-term drainage group. There were no statistically significant differences in age, gender, body mass index (BMI), hypertension, diabetes mellitus, surgery history of upper abdominal, American Society of Anesthesiologists (ASA) grade, carcinoembryonic antigen, carbohydrate antigen 125, alpha-fetoprotein, prothrombin time, pancreaticojejunostomy method, operation time, and pathological type between the two groups (all P > 0.05). However, patients in long-term drainage group had higher conversion rate, more blood loss and longer hospital stay compared with those in short-term drainage group (all P < 0.05). Before biliary drainage, alanine aminotransferase (ALT) level in short-term drainage group was higher than that in long-term drainage group ( Z = -2.59, P = 0.009), and there were no statistically significant differences in aspartate aminotransferase (AST), albumin (ALB), total bilirubin (TB) and direct bilirubin (DB) levels between the two groups before biliary drainage (all P > 0.05). After biliary drainage, DB in short-term drainage group was higher than that in long-term drainage group ( Z = -3.34, P = 0.001), and there was no statistically significant difference in ALT, AST, ALB, TB levels between the two groups (all P > 0.05). There were no statistically significant differences in the levels of white blood cells, neutrophils, lymphocytes and the ratio of neutrophils to lymphocytes between the two groups on the 1st and 3rd day after the operation (all P > 0.05). The total incidence of postoperative related complications in short-term drainage group and long-term drainage group was 63.2% (43/68), 70.6% (24/34), respectively, and the difference was statistically significant ( χ2 = 0.54, P = 0.461); the incidences of bile leakage, abdominal or gastrointestinal bleeding, intra-abdominal infection, delayed gastric emptying, all grades of pancreatic leakage, grade B and C pancreatic leakage were not statistically different between the two groups (all P > 0.05); the incidence of severe postoperative related complications in short-term drainage group was higher than that in long-term drainage group [27.9% (19/68) vs. 8.8% (3/34), χ2 = 4.90, P = 0.027]. Multivariate logistic regression analysis showed that the long-term preoperative biliary drainage was an independent protective factor for postoperative severe complications (long-term drainage vs. short-term drainage: OR = 0.253, 95% CI 0.066-0.975, P = 0.046), while BMI ( OR = 1.174, 95% CI 0.986-1.398, P = 0.071) and pathological type (benign or borderline vs. malignant tumor: OR = 0.247, 95% CI 0.043-1.419, P = 0.117) were not independent influencing factors for postoperative severe complications. Conclusions:Short-term biliary drainage (≤14 d) is a risk factor for postoperative severe complications in patients with hepatopancreatic ductal periampullary tumor undergoing preoperative biliary drainage. Preoperative biliary drainage time is not associated with postoperative total complications, pancreatic leakage, bile leakage, abdominal or gastrointestinal bleeding, intra-abdominal infection, delayed gastric emptying.
5.Whole Genome Analyses of Chinese Population and De Novo Assembly of A Northern Han Genome.
Zhenglin DU ; Liang MA ; Hongzhu QU ; Wei CHEN ; Bing ZHANG ; Xi LU ; Weibo ZHAI ; Xin SHENG ; Yongqiao SUN ; Wenjie LI ; Meng LEI ; Qiuhui QI ; Na YUAN ; Shuo SHI ; Jingyao ZENG ; Jinyue WANG ; Yadong YANG ; Qi LIU ; Yaqiang HONG ; Lili DONG ; Zhewen ZHANG ; Dong ZOU ; Yanqing WANG ; Shuhui SONG ; Fan LIU ; Xiangdong FANG ; Hua CHEN ; Xin LIU ; Jingfa XIAO ; Changqing ZENG
Genomics, Proteomics & Bioinformatics 2019;17(3):229-247
To unravel the genetic mechanisms of disease and physiological traits, it requires comprehensive sequencing analysis of large sample size in Chinese populations. Here, we report the primary results of the Chinese Academy of Sciences Precision Medicine Initiative (CASPMI) project launched by the Chinese Academy of Sciences, including the de novo assembly of a northern Han reference genome (NH1.0) and whole genome analyses of 597 healthy people coming from most areas in China. Given the two existing reference genomes for Han Chinese (YH and HX1) were both from the south, we constructed NH1.0, a new reference genome from a northern individual, by combining the sequencing strategies of PacBio, 10× Genomics, and Bionano mapping. Using this integrated approach, we obtained an N50 scaffold size of 46.63 Mb for the NH1.0 genome and performed a comparative genome analysis of NH1.0 with YH and HX1. In order to generate a genomic variation map of Chinese populations, we performed the whole-genome sequencing of 597 participants and identified 24.85 million (M) single nucleotide variants (SNVs), 3.85 M small indels, and 106,382 structural variations. In the association analysis with collected phenotypes, we found that the T allele of rs1549293 in KAT8 significantly correlated with the waist circumference in northern Han males. Moreover, significant genetic diversity in MTHFR, TCN2, FADS1, and FADS2, which associate with circulating folate, vitamin B12, or lipid metabolism, was observed between northerners and southerners. Especially, for the homocysteine-increasing allele of rs1801133 (MTHFR 677T), we hypothesize that there exists a "comfort" zone for a high frequency of 677T between latitudes of 35-45 degree North. Taken together, our results provide a high-quality northern Han reference genome and novel population-specific data sets of genetic variants for use in the personalized and precision medicine.
6.Advances of long-acting recombinant protein therapeutics.
Ying WEI ; Zhewen ZHANG ; Yamin LU ; Yanju CHENG
Chinese Journal of Biotechnology 2018;34(3):360-368
Some of the recombinant protein therapeutics with short half-life requires high frequent dose or injection, which results in poor patient compliance. This challenge has prompted the development of long-acting recombinant proteins in recent years. Four strategies and methods, including chemical modification, protein engineering, fusion proteins and protein glycosylation are used to modify protein molecule and finally obtain improved pharmacokinetics (PK) properties. This article reviews the four strategies of half-life extension and presents a detailed list of long-acting therapeutics on US, EU and China markets.
7.Advances of the effects of antibody heterogeneity on the function and metabolism of monoclonal antibody drugs
Chen WANG ; Zhewen ZHANG ; Yingchun LI ; Xiquan ZHANG ; Wei ZHAO
Journal of China Pharmaceutical University 2017;48(5):614-621
Antibody drugs often show "heterogeneity",including the related isomers differing from one another in glycosylation,charge or molecular size.Most of these isomers come from post-translational modifications,such as aggregation,degradation,glycosylation,oxidation,deamidation or disulfide misfolding,of the recombinant protein in the "cell factories".These modifications not only influence the quality,safety and efficacy of the antibodies,but also serve as an important indication of product quality throughout the whole process of antibody production.This paper reviews the relationship between glycoslation,charge and size heterogeneities of monoclonal antibodies and drug efficacy,safety,pharmacokinetics as well as immunogenicity,contributing to a better understanding of the relationship between antibody structure and function.It will provide some support and guidance for the research and development of antibody drugs,especially biosimilars.

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