Four lathyrane diterpenoids from the seeds of Euphorbia lathyris.

Four new diterpenoids, including three secolathyrane diterpenoids (1-3) and one lathyrane diterpenoid (4), together with seven known diterpenoids, were obtained in the shelled seeds of Euphorbia lathyris. In particular, 1-3 possess a rare split ring structure, and currently only one compound with the same skeleton has been identified in E. lathyris. Compound 4 furnishes an unprecedented oxygen bridge structure. The structures were identified using various spectral techniques, including NMR, HR-ESI-MS, single-crystal X-ray diffraction and calculated electronic circular dichroism (ECD). The biosynthetic pathway of 1-4 was inferred. Furthermore, the cytotoxic activities of all compounds (1-11) were measured on three human tumor cells. New compounds 2 and 3 showed moderate cytotoxic activities against U937 cells with IC50 values of 22.18 and 25.41 µM, respectively.

DePARylation is critical for S phase progression and cell survival.

Poly(ADP-ribose)ylation or PARylation by PAR polymerase 1 (PARP1) and dePARylation by poly(ADP-ribose) glycohydrolase (PARG) are equally important for the dynamic regulation of DNA damage response. PARG, the most active dePARylation enzyme, is recruited to sites of DNA damage via pADPr-dependent and PCNA-dependent mechanisms. Targeting dePARylation is considered an alternative strategy to overcome PARP inhibitor resistance. However, precisely how dePARylation functions in normal unperturbed cells remains elusive. To address this challenge, we conducted multiple CRISPR screens and revealed that dePARylation of S phase pADPr by PARG is essential for cell viability. Loss of dePARylation activity initially induced S-phase-specific pADPr signaling, which resulted from unligated Okazaki fragments and eventually led to uncontrolled pADPr accumulation and PARP1/2-dependent cytotoxicity. Moreover, we demonstrated that proteins involved in Okazaki fragment ligation and/or base excision repair regulate pADPr signaling and cell death induced by PARG inhibition. In addition, we determined that PARG expression is critical for cellular sensitivity to PARG inhibition. Additionally, we revealed that PARG is essential for cell survival by suppressing pADPr. Collectively, our data not only identify an essential role for PARG in normal proliferating cells but also provide a potential biomarker for the further development of PARG inhibitors in cancer therapy.

First Report of Colletotrichum gloeosporioides Causing Anthracnose on Euphorbia lathyris in China.

Euphorbia lathyris L. is a biennial herb in the Euphorbiaceae that has been used as a medicinal plant. It is distributed or cultivated worldwide, and the seeds of E. lathyris are the main source of ingenol, which is the precursor of Picato, the first medicine approved by USFDA for the treatment of solar keratosis (Abramovits et al. 2013). However, the production of E. lathyris can be severely hampered by the occurrence of plant diseases. Between 2020-2022 (specifically in October-November of each year), anthracnose-like symptoms were observed on E. lathyris in fields (E 118°49'50″, N 32°3'33″) in Nanjing, Jiangsu Province, China. The incidence of E. lathyris with disease symptoms was between 25%-30% (n = 100). The lesions on the leaves were evident initially as dark brown spots, which expanded into larger necrotic spots, finally resulting in leaves withering and dropping off. In severe cases, stem wilting was also observed. To determine the causal agent, we collected diseased leaf samples (n = 20) from different E. lathyris plants in the field (~ 1800 m2). After cleaning, the junctions of the diseased and healthy parts were excised and sterilized in 75% ethanol for 20-25 seconds, and rinsed with sterile water. After that, they were transferred onto potato sucrose agar (PSA) plates and placed at 25℃ for 3-4 days, until fungal growth was evident. The fungus was purified by recovering single conidia and growing them on PSA (Hu et al. 2015). A consistent fungal colony, based on morphological characteristics, was recovered from 17 samples. The colony color was initially white, green in the middle, and gradually changed into gray green as the colony matured. Conidia were transparent and cylindrical (22-28 µm × 7-9 µm, n = 50). Five loci informative (ITS, TUB, ACT, GAPDH, and CHS-1) (Weir et al. 2012) for Colletotrichum spp. identification were sequenced from two isolates ELC-1 and ELC-2 obtained from different plant individuals. Compared with a reference isolate (Colletotrichum gloeosporioides ZH3), the GAPDH, CHS-1, and TUB2 sequences of ELC-1 and ELC-2 showed 95% (263 bp out of 275 bp), 98% (295 bp out of 299 bp), and 99% (711 bp out of 712 bp and 717 bp out of 719 bp) similarity, respectively. The ITS sequence identities were 100% (577 bp out of 577 bp) and 99% (594 bp out of 597 bp), while the ACT sequence identities were 100% (281 bp out of 281 bp) and 98% (279 bp out of 284 bp). All sequences have been deposited in Genbank database (OR865865-OR865866 and OR873625-OR873632). After performing phylogenetic analysis with Mega 11, the pathogen was confirmed as C. gloeosporioides. To fulfil Koch's postulates, we sprayed six-week-old healthy plants with a conidia suspension of C. gloeosporioides (106 spores/mL) or sterile water (serve as control). The inoculated plants were placed at 25℃, 100% relative humidity, and 12-h photoperiod (Zhang et al. 2021). Six plants were inoculated for each treatment, and the experiment was repeated three times. After 6-8 days, the plants inoculated with C. gloeosporioides showed similar symptoms to those observed on diseased plants in the field, while the control plants remained healthy and free of disease. The pathogens were then re-isolated and identified as C. gloeosporioides. To our knowledge, this is the first report of C. gloeosporioides causing anthracnose on E. lathyris. Anthracnose may cause significant yield losses in E. lathyris production, and our results will provide experimental and theoretical basis for the management of the disease.

Comprehensive Analysis of 11 Species of Euodia (Rutaceae) by Untargeted LC-IT-TOF/MS Metabolomics and In Vitro Functional Methods.

The Euodia genus comprises numerous untapped medicinal plants that warrant thorough evaluation for their potential as valuable natural sources of herbal medicine or food flavorings. In this study, untargeted metabolomics and in vitro functional methods were employed to analyze fruit extracts from 11 significant species of the Euodia genus. An investigation of the distribution of metabolites (quinolone and indole quinazoline alkaloids) in these species indicated that E. rutaecarpa (Euodia rutaecarpa) was the most widely distributed species, followed by E. compacta (Euodia compacta), E. glabrifolia (Euodia glabrifolia), E. austrosinensis (Euodia austrosinensis), and E. fargesii (Euodia fargesii). There have been reports on the close correlation between indole quinazoline alkaloids and their anti-tumor activity, especially in E. rutaecarpa fruits which exhibit effectiveness against various types of cancer, such as SGC-7901, Hela, A549, and other cancer cell lines. Additionally, the E. rutaecarpa plant contains indole quinazoline alkaloids, which possess remarkable antibacterial properties. Our results offer novel insights into the utilization of Euodia resources in the pharmaceutical industry.

Genome-wide CRISPR screen reveals the synthetic lethality between BCL2L1 inhibition and radiotherapy.

Radiation therapy (RT) is one of the most commonly used anticancer therapies. However, the landscape of cellular response to irradiation, especially to a single high-dose irradiation, remains largely unknown. In this study, we performed a whole-genome CRISPR loss-of-function screen and revealed temporal inherent and acquired responses to RT. Specifically, we found that loss of the IL1R1 pathway led to cellular resistance to RT. This is in part because of the involvement of radiation-induced IL1R1-dependent transcriptional regulation, which relies on the NF-κB pathway. Moreover, the mitochondrial anti-apoptotic pathway, particularly the BCL2L1 gene, is crucially important for cell survival after radiation. BCL2L1 inhibition combined with RT dramatically impeded tumor growth in several breast cancer cell lines and syngeneic models. Taken together, our results suggest that the combination of an apoptosis inhibitor such as a BCL2L1 inhibitor with RT may represent a promising anticancer strategy for solid cancers including breast cancer.

Identification of One O-Methyltransferase Gene Involved in Methylated Flavonoid Biosynthesis Related to the UV-B Irradiation Response in Euphorbia lathyris.

Flavonoids are ubiquitous polyphenolic compounds that play a vital role in plants' defense response and medicinal efficacy. UV-B radiation is a vital environmental regulator governing flavonoid biosynthesis in plants. Many plants rapidly biosynthesize flavonoids as a response to UV-B stress conditions. Here, we investigated the effects of flavonoid biosynthesis via UV-B irradiation in Euphorbia lathyris. We found that exposure of the E. lathyris callus to UV-B radiation sharply increased the level of one O-methyltransferase (ElOMT1) transcript and led to the biosynthesis of several methylated flavonoids. The methyltransferase ElOMT1 was expressed heterologously in E. coli, and we tested the catalytic activity of recombinant ElOMT1 with possible substrates, including caffeic acid, baicalin, and luteolin, in vitro. ElOMT1 could efficiently methylate when the hydroxyl groups were contained in the core nucleus of the flavonoid. This molecular characterization identifies a methyltransferase responsible for the chemical modification of the core flavonoid structure through methylation and helps reveal the mechanism of methylated flavonoid biosynthesis in Euphorbiaceae. This study identifies the O-methyltransferase that responds to UV-B irradiation and helps shed light on the mechanism of flavonoid biosynthesis in Euphorbia lathyris.

Genome-Wide Identification and Expression Profiling of Potato (Solanum tuberosum L.) Universal Stress Proteins Reveal Essential Roles in Mechanical Damage and Deoxynivalenol Stress.

Universal stress proteins (USPs) play an important regulatory role in responses to abiotic stress. Most of the research related to USPs so far has been conducted on plant models such as Arabidopsis (Arabidopsis thaliana), rice (Oryza sativa L.), and cotton (Gossypium hirsutum L.). The potato (Solanum tuberosum L.) is one of the four major food crops in the world. The potato is susceptible to mechanical damage and infection by pathogenic fungi during transport and storage. Deoxynivalenol (DON) released by Fusarium can seriously degrade the quality of potatoes. As a result, it is of great significance to study the expression pattern of the potato StUSP gene family under abiotic stress conditions. In this study, a total of 108 USP genes were identified from the genome of the Atlantic potato, divided into four subgroups. Based on their genetic structure, the physical and chemical properties of their proteins and other aspects of their biological characteristics are comprehensively analyzed. Collinear analysis showed that the homologous genes of StUSPs and four other representative species (Solanum lycopersicum, Arabidopsis, Oryza sativa L., and Nicotiana attenuata) were highly conserved. The cis-regulatory elements of the StUSPs promoter are involved in plant hormones, environmental stress, mechanical damage, and light response. RNA-seq analysis showed that there are differences in the expression patterns of members of each subgroup under different abiotic stresses. A Weighted Gene Coexpression Network Analysis (WGCNA) of the central gene showed that the differential coexpression gene is mainly involved in the plant-pathogen response process, plant hormone signal transduction, and the biosynthesis process of secondary metabolites. Through qRT-PCR analysis, it was confirmed that StUSP13, StUSP14, StUSP15, and StUSP41 may be important candidate genes involved in the response to adversity stress in potatoes. The results of this study provide a basis for further research on the functional analysis of StUSPs in the response of potatoes to adversity stress.

Magnetic resonance imaging-guided radiofrequency ablation of breast cancer: a current state of the art review.

With a gradual increase in breast cancer incidence and mortality rates and an urgent need to improve patient prognosis and cosmetology, magnetic resonance imaging (MRI)-guided radiofrequency ablation (RFA) therapy has attracted wide attention as a new treatment method for breast cancer. MRI-RFA results in a higher complete ablation rate and extremely low recurrence and complication rates. Thus, it may be used as an independent treatment for breast cancer or adjuvant to breast-conserving surgery to reduce the extent of breast resection. Furthermore, with MRI guidance, accurate control of RFA can be achieved, and breast cancer treatment can enter a new stage of minimally invasive, safe, and comprehensive therapy. With progress in MR thermometry technology, the applications of MRI are expected to broaden.

DePARylation is critical for S phase progression and cell survival.

Poly(ADP-ribose)ylation or PARylation by PAR polymerase 1 (PARP1) and dePARylation by poly(ADP-ribose) glycohydrolase (PARG) are equally important for the dynamic regulation of DNA damage response. PARG, the most active dePARylation enzyme, is recruited to sites of DNA damage via pADPr-dependent and PCNA-dependent mechanisms. Targeting dePARylation is considered an alternative strategy to overcome PARP inhibitor resistance. However, precisely how dePARylation functions in normal unperturbed cells remains elusive. To address this challenge, we conducted multiple CRISPR screens and revealed that dePARylation of S phase pADPr by PARG is essential for cell viability. Loss of dePARylation activity initially induced S phase-specific pADPr signaling, which resulted from unligated Okazaki fragments and eventually led to uncontrolled pADPr accumulation and PARP1/2-dependent cytotoxicity. Moreover, we demonstrated that proteins involved in Okazaki fragment ligation and/or base excision repair regulate pADPr signaling and cell death induced by PARG inhibition. In addition, we determined that PARG expression is critical for cellular sensitivity to PARG inhibition. Additionally, we revealed that PARG is essential for cell survival by suppressing pADPr. Collectively, our data not only identify an essential role for PARG in normal proliferating cells but also provide a potential biomarker for the further development of PARG inhibitors in cancer therapy.

Simultaneous tensile and shear measurement of the human cornea in vivo using S0- and A0-wave optical coherence elastography.

Understanding corneal stiffness is valuable for improving refractive surgery, detecting corneal abnormalities, and assessing intraocular pressure. However, accurately measuring the elastic properties, specifically the tensile and shear moduli that govern mechanical deformation, has been challenging. To tackle this issue, we have developed guided-wave optical coherence elastography that can simultaneously excite and analyze symmetric (S0) and anti-symmetric (A0) elastic waves in the cornea at around 10 kHz frequencies, enabling us to extract tensile and shear properties from measured wave dispersion curves. We verified the technique using elastomer phantoms and ex vivo porcine corneas and investigated the dependence on intraocular pressure using acoustoelastic theory that incorporates corneal tension and a nonlinear constitutive tissue model. In a pilot study involving six healthy human subjects aged 31 to 62, we measured shear moduli (Gzx) of 94±20 kPa (mean±standard deviation) and tensile moduli (Exx) of 4.0±1.1 MPa at central corneas. Our preliminary analysis of age-dependence revealed contrasting trends: -8.3±4.5 kPa/decade for shear and 0.30±0.21 MPa/decade for tensile modulus. This OCE technique has the potential to become a highly useful clinical tool for the quantitative biomechanical assessment of the cornea. STATEMENT OF SIGNIFICANCE: This article reports an innovative elastography technique using two guided elastic waves, demonstrating the measurement of both tensile and shear moduli in human cornea in vivo with unprecedented precision. This technique paves the way for comprehensive investigations into corneal mechanics and holds clinical significance in various aspects of corneal health and disease management.

Postoperative delirium prediction after cardiac surgery using machine learning models.

OBJECTIVE: Postoperative delirium (POD) is a common postoperative complication in elderly patients, especially those undergoing cardiac surgery, which seriously affects the short- and long-term prognosis of patients. Early identification of risk factors for the development of POD can help improve the perioperative management of surgical patients. In the present study, five machine learning models were developed to predict patients at high risk of delirium after cardiac surgery and their performance was compared. METHODS: A total of 367 patients who underwent cardiac surgery were retrospectively included in this study. Using single-factor analysis, 21 risk factors for POD were selected for inclusion in machine learning. The dataset was divided using 10-fold cross-validation for model training and testing. Five machine learning models (random forest (RF), support vector machine (SVM), radial based kernel neural network (RBFNN), K-nearest neighbour (KNN), and Kernel ridge regression (KRR)) were compared using area under the receiver operating characteristic curve (AUC-ROC), accuracy (ACC), sensitivity (SN), specificity (SPE), and Matthews coefficient (MCC). RESULTS: Among 367 patients, 105 patients developed POD, the incidence of delirium was 28.6 %. Among the five ML models, RF had the best performance in ACC (87.99 %), SN (69.27 %), SPE (95.38 %), MCC (70.00 %) and AUC (0.9202), which was far superior to the other four models. CONCLUSION: Delirium is common in patients after cardiac surgery. This analysis confirms the importance of the computational ML models in predicting the occurrence of delirium after cardiac surgery, especially the outstanding performance of the RF model, which has practical clinical applications for early identification of patients at risk of developing POD.

Bone Marrow-Derived GCA+ Immune Cells Drive Alzheimer's Disease Progression.

Alzheimer's disease (AD) is an age-related degenerative disease of the central nervous system (CNS), whereas the role of bone marrow immune cells in the pathogenesis of AD remains unclear. Here, the study reveals that compared to matched healthy individuals, AD patients have higher circulating grancalcin (GCA) levels, which negatively correlate with cognitive function. Bone marrow-derived GCA+ immune cells, which secret abundant GCA and increase during aging, preferentially invaded the hippocampus and cortex of AD mouse model in a C-C Motif Chemokine Receptor 10 (CCR10)-dependent manner. Transplanting GCA+ immune cells or direct stereotaxic injection of recombinant GCA protein intensified amyloid plaque load and aggravated cognitive and memory impairments. In contrast, genetic ablation of GCA in the hematopoietic compartment improves cognitive and memory function. Mechanistically, GCA competitively binds to the low-density lipoprotein receptor-related protein 1 (LRP1) in microglia, thus inhibiting phagocytosis and clearance of Aß and potentiating neuropathological changes. Importantly, GCA-neutralizing antibody treatment rejuvenated cognitive and memory function and constrained AD progression. Together, the study demonstrates a pathological role of GCA+ immune cells instigating cognitive and memory decline, suggesting that GCA+ immune cells can be a potential target for innovative therapeutic strategies in AD.

Bone marrow immune cells respond to fluctuating nutritional stress to constrain weight regain.

Weight regain after weight loss is a major challenge in the treatment of obesity. Immune cells adapt to fluctuating nutritional stress, but their roles in regulating weight regain remain unclear. Here, we identify a stem cell-like CD7+ monocyte subpopulation accumulating in the bone marrow (BM) of mice and humans that experienced dieting-induced weight loss. Adoptive transfer of CD7+ monocytes suppresses weight regain, whereas inducible depletion of CD7+ monocytes accelerates it. These cells, accumulating metabolic memories via epigenetic adaptations, preferentially migrate to the subcutaneous white adipose tissue (WAT), where they secrete fibrinogen-like protein 2 (FGL2) to activate the protein kinase A (PKA) signaling pathway and facilitate beige fat thermogenesis. Nevertheless, CD7+ monocytes gradually enter a quiescent state after weight loss, accompanied by increased susceptibility to weight regain. Notably, administration of FMS-like tyrosine kinase 3 ligand (FLT3L) remarkably rejuvenates CD7+ monocytes, thus ameliorating rapid weight regain. Together, our findings identify a unique bone marrow-derived metabolic-memory immune cell population that could be targeted to combat obesity.

Simultaneous tensile and shear measurement of the human cornea in vivo using S0- and A0-wave optical coherence elastography.

Understanding corneal stiffness is valuable for improving refractive surgery, detecting corneal abnormalities, and assessing intraocular pressure. However, accurately measuring the elastic properties, particularly the tensile and shear moduli that govern mechanical deformation, has been challenging. To tackle this issue, we have developed guided-wave optical coherence elastography that can simultaneously excite and analyze symmetric (S0) and anti-symmetric (A0) elastic waves in the cornea at frequencies around 10 kHz and allows us to extract tensile and shear properties from measured wave dispersion curves. By applying acoustoelastic theory that incorporates corneal tension and a nonlinear constitutive tissue model, we verified the technique using elastomer phantoms and ex vivo porcine corneas and investigated the dependence on intraocular pressure. For two healthy human subjects, we measured a mean tensile modulus of 3.6 MPa and a mean shear modulus of 76 kPa in vivo with estimated errors of < 4%. This technique shows promise for the quantitative biomechanical assessment of the cornea in a clinical setting.

MatBED_B&C: A 3-dimensional biologically effective dose analytic approach for the retrospective study of gamma knife radiosurgery in a B&C model.

The biological effect of irradiation is not solely determined by the physical dose. Gamma knife radiosurgery may be influenced by dose rate, beam-on-time, numbers of iso-centers, the gap between the individual iso-centers, and the dose‒response of various tissues. The biologically effective dose (BED) for radiosurgery considers these issues. Millions of patients treated with Models B and C provide a vast database to mine BED-related information. This research aims to develop MatBED_B&C, a 3-dimensional (3D) BED analytic approach, to generate a BED for individual voxels in the calculation matrix with related parameters extracted from Gammaplan. This approach calculates the distribution profiles of the BED in radiosurgical targets and organs at risk. A BED calculated on a voxel-by-voxel basis can be used to show the 3D morphology of the iso-BED surface and visualize the BED spatial distribution in the target. A 200 × 200 × 200 matrix can cover a greater range of the organ at risk. The BED calculated by MatBED_B&C can also be used to form BED-volume histograms to generate plan quality metrics, which will be studied in a retrospective study of gamma knife radiosurgery to guide future BED planning.•We develop MatBED_B&C to calculate the 3D BED in radiosurgical targets.•The BED of MatBED_B&C can visualize the BED spatial distribution profiles.•The BED of MatBED_B&C will generate plan quality metrics studied in a retrospective study.

Development and validation of a risk prediction algorithm for evaluating the efficacy of postoperative adjuvant TACE therapy for hepatocellular carcinoma.

BACKGROUND AND PURPOSE: There is a lack of a reliable outcome prediction model for patients evaluating the feasibility of postoperative adjuvant transarterial chemoembolization (PA-TACE) therapy. Our goal was to develop an easy-to-use tool specifically for these patients. METHODS: From January 2013 to June 2017, patients with hepatocellular carcinoma from the Liver Center of the First Affiliated Hospital of Chongqing Medical University received postoperative adjuvant Transarterial chemoembolization (TACE) therapy after liver cancer resection. A Cox proportional hazards model was established for these patients, followed by internal validation (enhanced bootstrap resampling technique) to further evaluate the predictive performance and discriminanceevaluate the predictive performance and discriminance, and compare it with other predictive models. The prognostic factors considered included tumour number, maximum tumor diameter, Edmondson-Steiner (ES) grade, Microvascular invasion (MVI) grade, Ki67, age, sex, hepatitis B surface antigen, cirrhosis, Alpha-fetoprotein(AFP), Albumin-bilirubin (ALBI) grade, Child-pugh grade, body mass index (BMI), Neutrophil-lymphocyte ratio (NLR), Platelet-to-lymphocyte ratio (PLR). RESULTS: The endpoint of the study was overall survival. The median overall survival was 36 (95%CI: 34.0-38.0 ) months, with 1-year, 2-year and 3-year survival rates being 96.3%, 84.0% and 75.3%, respectively. Tumour number, MVI grade, and BMI was incorporated into the model, which had good differentiation and accuracy. Internal validation (enhanced bootstrap ) suggested that Harrell's C statistic is 0.72. The model consistently outperforms other currently available models. CONCLUSION: This model may be an easy-to-use tool for screening patients suitable for PA-TACE treatment and guiding the selection of clinical protocols. But further research and external validation are required.

Comparison of short-term outcomes between robotic and laparoscopic distal gastrectomy performed by the same surgical team during the same period.

Objective: To evaluate the short-term outcomes of laparoscopic distal gastrectomy and robotic distal gastrectomy performed during the same period. Methods: This study enrolled 46 cases of laparoscopic distal gastrectomy and 67 cases of robotic distal gastrectomy that were performed by a single surgeon between April 2020 to October 2021. Baseline characteristics and short-term outcomes of these two groups were then compared. Moreover, the robotic distal gastrectomy group was further divided into two subgroups according to the learning curve. Finally, the baseline characteristics and short-term outcomes of both subgroups were compared with the laparoscopic group, respectively. Results: The baseline characteristics and short-term outcomes of the LDG group and RDG group were comparable. In contrast, the operation time in the laparoscopic group was significantly shorter than that in the early experience robotic group (191.3 ± 37.6 VS 225.1 ± 49, P=0.001). However, the operation time (191.3 ± 37.6 VS 185.3 ± 25.3, P=0.434) was comparable between the laparoscopic group and the late experience robotic group. Likewise, the bleeding volume was comparable between the laparoscopic and early experience robotic groups. However, bleeding volume was significantly lower in the late experience robotic group compared to that in the laparoscopic group (37.5 ± 18.8 VS 49.2 ± 29.0, P=0.049). Conclusions: With surgeons stepping into the stable stage of the robotic learning curve, RDG showed a comparable operation time and lower volume of blood loss compared with LDG. Collectively, our study supports the application of robotic distal gastrectomy in patients diagnosed with gastric cancer.

Wedge resection versus segment IVb and V resection of the liver for T2 gallbladder cancer: a systematic review and meta-analysis.

Objectives: Although guidelines recommend extended cholecystectomy for T2 gallbladder cancer (GBC), the optimal hepatectomy strategy remains controversial. The study aims to compare the prognosis of T2 GBC patients who underwent wedge resection (WR) versus segment IVb and V resection (SR) of the liver. Methods: A specific search of online databases was performed from May 2001 to February 2023. The postoperative efficacy outcomes were synthesized and meta-analyses were conducted. Results: A total of 9 studies involving 2,086 (SR = 627, WR = 1,459) patients were included in the study. The primary outcomes included disease-free survival (DFS) and overall survival (OS). For DFS, the 1-year DFS was statistically higher in patients undergoing SR than WR [risk ratio (RR) = 1.07, 95% confidence interval (CI) = 1.02-1.13, P = 0.007]. The 3-year DFS (P = 0.95), 5-year DFS (P = 0.77), and hazard ratio (HR) of DFS (P = 0.72) were similar between the two groups. However, the 3-year OS was significantly lower in patients who underwent SR than WR [RR = 0.90, 95% CI = 0.82-0.99, P = 0.03]. Moreover, SR had a higher hazard HR of OS [HR = 1.33, 95% CI = 1.01-1.75, P = 0.04]. No significant difference was found in 1-year (P = 0.32) and 5-year (P = 0.9) OS. For secondary outcomes, patients who received SR tended to develop postoperative complications (POC) [RR = 1.90, 95% CI = 1.00-3.60, P = 0.05]. In addition, no significant differences in intrahepatic recurrence (P = 0.12) were observed. Conclusions: In conclusion, SR can improve the prognosis of T2 GBC patients in DFS. In contrast to WR, the high HR and complications associated with SR cannot be neglected. Therefore, surgeons should evaluate the condition of the patients and take their surgical skills into account when selecting SR. Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier, CRD42022362974.