Kaempferide ameliorates cisplatin-induced nephrotoxicity via inhibiting oxidative stress and inducing autophagy.

Acute kidney injury (AKI) caused by anti-tumor drugs, such as cisplatin, is a severe complication with no effective treatment currently, leading to the reduction or discontinuation of chemotherapy. Natural products or herbal medicines are gradually considered as promising agents against cisplatin-induced AKI with the advantages of multi-targeting, multi-effects, and less resistance. In this study, we investigated the effects of kaempferide, a natural flavonoid extracted from the rhizome of Kaempferia galanga, in experimental AKI models in vitro and in vivo. We first conducted pharmacokinetic study in mice and found a relative stable state of kaempferide with a small amount of conversion into kaempferol. We showed that both kaempferide (10 µM) and kaempferol (10 µM) significantly inhibited cisplatin-caused injuries in immortalized proximal tubule epithelial cell line HK-2. In AKI mice induced by injection of a single dose of cisplatin (15 mg/kg), oral administration of kaempferide (50 mg/kg) either before or after cisplatin injection markedly improved renal function, and ameliorated renal tissue damage. We demonstrated that kaempferide inhibited oxidative stress and induced autophagy in cisplatin-treated mice and HK-2 cells, thus increasing tubular cell viability and decreasing immune responses to attenuate the disease progression. In addition, treatment with kaempferide significantly ameliorated ischemia-reperfusion-induced renal injury in vitro and in vivo. We conclude that kaempferide is a promising natural product for treating various AKI. This study has great implications for promotion of its use in healthcare products, and help to break through the limited use of cisplatin in the clinic.

Sapidolide A alleviates acetaminophen-induced acute liver injury by inhibiting NLRP3 inflammasome activation in macrophages.

Macrophages play a critical role in the pathogenesis of acetaminophen (APAP)-induced liver injury (AILI), a major cause of acute liver failure or even death. Sapidolide A (SA) is a sesquiterpene lactone extracted from Baccaurea ramiflora Lour., a folk medicine used in China to treat inflammatory diseases. In this study, we investigated whether SA exerted protective effects on macrophages, thus alleviated the secondary hepatocyte damage in an AILI. We showed that SA (5-20 µM) suppressed the phosphorylated activation of NF-κB in a dose-dependent manner, thereby inhibiting the expression and activation of the NOD-like receptor protein 3 (NLRP3) inflammasome and pyroptosis in LPS/ATP-treated mouse bone marrow-derived primary macrophages (BMDMs). In human hepatic cell line L02 co-cultured with BMDMs, SA (10 µM) protected macrophages from the pyroptosis induced by APAP-damaged L02 cells. Moreover, SA treatment reduced the secondary liver cell damage aggravated by the conditioned medium (CM) taken from LPS/ATP-treated macrophages. The in vivo assessments conducted on mice pretreated with SA (25, 50 mg/kg, ip) then with a single dose of APAP (400 mg/kg, ip) showed that SA significantly alleviated inflammatory responses of AILI by inhibiting the expression and activation of the NLRP3 inflammasome. In general, the results reported herein revealed that SA exerts anti-inflammatory effects by regulating NLRP3 inflammasome activation in macrophages, which suggests that SA has great a potential for use in the treatment of AILI patients.

Natural products: potential treatments for cisplatin-induced nephrotoxicity.

Cisplatin is a clinically advanced and highly effective anticancer drug used in the treatment of a wide variety of malignancies, such as head and neck, lung, testis, ovary, breast cancer, etc. However, it has only a limited use in clinical practice due to its severe adverse effects, particularly nephrotoxicity; 20%-35% of patients develop acute kidney injury (AKI) after cisplatin administration. The nephrotoxic effect of cisplatin is cumulative and dose dependent and often necessitates dose reduction or withdrawal. Recurrent episodes of AKI result in impaired renal tubular function and acute renal failure, chronic kidney disease, uremia, and hypertensive nephropathy. The pathophysiology of cisplatin-induced AKI involves proximal tubular injury, apoptosis, oxidative stress, inflammation, and vascular injury in the kidneys. At present, there are no effective drugs or methods for cisplatin-induced kidney injury. Recent in vitro and in vivo studies show that numerous natural products (flavonoids, saponins, alkaloids, polysaccharide, phenylpropanoids, etc.) have specific antioxidant, anti-inflammatory, and anti-apoptotic properties that regulate the pathways associated with cisplatin-induced kidney damage. In this review we describe the molecular mechanisms of cisplatin-induced nephrotoxicity and summarize recent findings in the field of natural products that undermine these mechanisms to protect against cisplatin-induced kidney damage and provide potential strategies for AKI treatment.

Applications and advances of CRISPR-Cas9 in cancer immunotherapy.

Immunotherapy has emerged as one of the most promising therapeutic strategies in cancer. The clustered regularly interspaced short palindromic repeat (CRISPR)-associated protein 9 (CRISPR-Cas9) system, as an RNA-guided genome editing technology, is triggering a revolutionary change in cancer immunotherapy. With its versatility and ease of use, CRISPR-Cas9 can be implemented to fuel the production of therapeutic immune cells, such as construction of chimeric antigen receptor T (CAR-T) cells and programmed cell death protein 1 knockout. Therefore, CRISPR-Cas9 technology holds great promise in cancer immunotherapy. In this review, we will introduce the origin, development and mechanism of CRISPR-Cas9. Also, we will focus on its various applications in cancer immunotherapy, especially CAR-T cell-based immunotherapy, and discuss the potential challenges it faces.

Comprehensive treatments for hepatocellular carcinoma with portal vein tumor thrombosis.

Portal vein tumor thrombosis (PVTT) is one of the most common complications in hepatocellular carcinoma (HCC). HCC with PVTT usually indicates poor prognosis, which has a number of characteristics including a rapidly progressive disease course, worse liver function, complications connected with portal hypertension, and poorer tolerance to treatment. The exact mechanisms of PVTT remain unknown, even though some concerned signal transduction or molecular pathways have been identified. In western countries, sorafenib is the only recommended therapeutic strategy regardless of PVTT types. However, multiple treatment options including transhepatic arterial chemoembolization, hepatectomy, radiotherapy, and sorafenib available in the clinic. In this review, we enumerate and discuss therapeutics against patients with HCC having PVTT available in the clinic and put forward directions for future research.

Comparative study of laparoscopic-assisted and open total gastrectomy for Siewert Types II and III adenocarcinoma of the esophagogastric junction.

BACKGROUND: The potential advantages of laparoscopic-assisted total gastrectomy (LATG) compared with open total gastrectomy (OTG) for Siewert Types II and III adenocarcinoma of the esophagogastric junction (AEJ) are not very clear. Thus, the aim of this study was to investigate the surgical outcomes and potential advantages of LATG for Siewert Types II and III AEJ. METHODS: The clinical data of 75 patients (32 for LATG and 43 for OTG) with Siewert II or III AEJ from August 2009 to February 2014 were analyzed retrospectively. Patients were followed up by telephone or out-patient examination till August 2015. RESULTS: Two groups of patients were successfully performed with no perioperative death. The mean operation time was 3.23 ± 0.35 hr in LATG group, longer than the OTG group 2.83 ± 0.51 hr. The mean intraoperative bleeding was 122.7 ± 50.6 ml, less than the OTG group 219.2 ± 85.2 ml. The analgesics use was 3.00 ± 0.67 times in the LATG group, less than the OTG group 3.43 ± 1.03 times. The gastrointestinal function recovery time was 2.69 ± 0.46 days in the LATG group, shorter than the OTG group 3.42 ± 0.86 days. The mean postoperative hospital stay was 12.94 + 2.76 days in the LATG group, less than the OTG group 14.57 + 2.35 days (p < 0.05). CONCLUSIONS: LATG and OTG had no significant difference for Siewert II and III AEJ in terms of radical resection and tumor recurrence, but LATG is worthy to be promoted with less bleeding, less postoperative pain, faster recovery of gastrointestinal function, and shorter hospital stay.

Identification of TAF1, HNF4A, and CALM2 as potential therapeutic target genes for liver fibrosis.

The molecular mechanism of liver fibrosis caused by hepatitis C virus (HCV) is not clear. The aim of this study is to understand the molecular mechanism of liver fibrosis induced by HCV and to identify potential therapeutic targets for hepatic fibrosis. We analyzed gene expression patterns between high liver fibrosis and low liver fibrosis samples, and identified genes related to liver fibrosis. We identified TAF1, HNF4A, and CALM2 were related to the development of liver fibrosis. HNF4A is important for hepatic fibrogenesis, and upregulation of HNF4A is an ideal choice for treating liver fibrosis. The gene expression of CALM2 is significantly lower in liver fibrosis samples than nonfibrotic samples. TAF1 may serve as a biomarker for liver fibrosis. The results were further validated by an independent data set GSE84044. In summary, our study described changes in the gene expression during the occurrence and development of liver fibrosis. The TAF1, HNF4A, and CALM2 may serve as novel targets for the treatment of liver fibrosis.

T cell exhaustion in cancer: Mechanisms and clinical implications.

During chronic viral infection or cancer, the immune system usually induces a corresponding immune response against pathogens or cancer cells so as to prevent worsening disease. T cell exhaustion in which reduced and dysfunctional effector T cells lead to immune escape is one of the mechanisms that pathogens or cancer cells get rid of control from the immune system. In this review, we discuss some mechanisms associated with T cell exhaustion and enumerate current methods of reversing T cell exhaustion. We also summarize current targeted treatment strategies and put forward following aspects that required to research.

Malawer limb salvage surgery for the treatment of scapular chondrosarcoma.

Chondrosarcoma is a common malignant bone tumor, which accounts for 20% of all malignant bone tumors. It often occurs in the long bones, but the incidence of scapular chondrosarcoma is rare. Here, we describe a case of a large chondrosarcoma occurring in the scapula which was treated with Malawer limb salvage surgery. The patient retained considerable limb function after complete removal of the tumor tissue as assessed at the follow-up visit two years and ten months following surgery.

Controlled release by novel lysostaphin-loaded hydroxyapatite/chitosan composites.

Lysostaphin is highly effective on eliminating methicillin resistant Staphylococcus aureus (MRSA). In order to achieve controlled release of lysostaphin, a biocompatible drug carrier is needed. Hydroxyapatite/chitosan (HA/CS) composites were chosen to carry lysostaphin and sample composites with different weight ratios of HA to CS, including 80/20, 70/30, 60/40, and 40/60, were prepared. Multiple analyses were performed to determine the structural and physicochemical properties of the composites, including scanning electron microscopy, X-ray diffraction and Fourier transform infrared spectroscopy. We immersed HA/CS composites loaded with 1 wt% lysostaphin to test in vitro release activity and cultured MC3T3-E1 cells to carry out biocompatibility test. The result of the release behavior of the composites revealed that the controlled release of lysostaphin from 60/40 HA/CS composites was the highest release rate of (87.4 ± 2.8)%, which lasted for 120 hours. In biocompatibility testing, MC3T3-E1 cells were able to proliferate on the surface of these composites, and the extract liquid from the composites could increase the growth of the cells. These results demonstrate the controlled release of lysostaphin from HA/CS composites and their biocompatibility, suggesting the potential application of these composites to bone injury and infection applications.

Whole-brain in vivo base editing reverses behavioral changes in Mef2c-mutant mice.

Whole-brain genome editing to correct single-base mutations and reduce or reverse behavioral changes in animal models of autism spectrum disorder (ASD) has not yet been achieved. We developed an apolipoprotein B messenger RNA-editing enzyme, catalytic polypeptide-embedded cytosine base editor (AeCBE) system for converting C·G to T·A base pairs. We demonstrate its effectiveness by targeting AeCBE to an ASD-associated mutation of the MEF2C gene (c.104T>C, p.L35P) in vivo in mice. We first constructed Mef2cL35P heterozygous mice. Male heterozygous mice exhibited hyperactivity, repetitive behavior and social abnormalities. We then programmed AeCBE to edit the mutated C·G base pairs of Mef2c in the mouse brain through the intravenous injection of blood-brain barrier-crossing adeno-associated virus. This treatment successfully restored Mef2c protein levels in several brain regions and reversed the behavioral abnormalities in Mef2c-mutant mice. Our work presents an in vivo base-editing paradigm that could potentially correct single-base genetic mutations in the brain.

Comparison of three different surgical approaches for treatment of thoracolumbar burst fracture.

OBJECTIVE: The main treatment method used for thoracolumbar fractures is open reduction and internal fixation. Commonly there are three surgical approaches: anterior, posterior and paraspinal. We attempt to compare the three approaches based on our clinical data analysis. METHODS: A group of 94 patients with Denis type A or B thoracolumbar burst fracture between March 2008 and September 2010 were recruited in this study. These patients were treated by anterior-, posterior- or paraspinal-approach reduction with or without decompression. The fracture was fixed with titanium mesh and Z-plate via anterior approach (24 patients), screw and rod system via posterior approach (38 patients) or paraspinal approach (32 patients). Clinical evaluations included operation duration, blood loss, incision length, preoperative and postoperative Oswestry disability index (ODI). RESULTS: The average operation duration (94.1 min +/- 13.7 min), blood loss (86.7 ml +/-0.0 ml), length of incision (9.3 mm +/- 0.7 mm) and postoperative ODI (6 +/- 0.5) were significantly lower (P less than 0.05) in paraspinal approach group than in traditional posterior approach group (operation duration 94.1 min +/- 13.7 min, blood loss 143.3 ml +/-28.3 ml, length of incision 15.4 cm +/- 2.1 cm and ODI 12 +/- 0.7) and anterior approach group (operation duration 176.3 min +/- 20.7 min, blood loss 255.1 ml +/- 38.4 ml, length of incision 18.6 cm +/- 2.4 cm and ODI 13 +/- 2.4). There was not statistical difference in terms of Cobb angle on radiographs among the three approaches. CONCLUSION: The anterior approach surgery is convenient for resection of the vertebrae and reconstruction of vertebral height, but it is more complicated and traumatic. Hence it is mostly used for severe Denis type B fracture. The posterior approach is commonly applied to most thoracolumbar fractures and has fewer complications compared with the anterior approach, but it has some shortcomings as well. The paraspinal approach has great advantages compared with the other two approaches. It is in accordance with the concept of minimally invasive surgery and can replace most posterior approach operations.

Zinc finger X-chromosomal protein promotes growth and tumorigenesis in human osteosarcoma cells.

OBJECTIVE: To investigate the role of Zinc finger X-chromosomal protein (ZFX) in oncogenesis of Osteosarcoma tumor. METHODS: Here, we first conducted an expression analysis of ZFX in Osteosarcoma cell lines. Then, we constructed ZFX-specific small interfering RNA (siRNA)-lentiviral vector that is capable of effectively inhibiting the expression of ZFX gene in human Osteosarcoma Saos-2 cells, and investigated systemically the impacts of ZFX silence on the growth and invasive ability of the cancer cells in vitro. Furthermore, we determined the effects of ZFX knockdown on the cell cycle distribution and apoptosis of Saos-2 cells. RESULTS: We found that ZFX inhibition resulted in significantly impaired proliferation and colony formation as well as mitigated invasiveness of Saos-2 cells. Importantly, si-ZFX infected cells exhibited a greater portion of cells at G1 phase, but a minor portion of S and G2/M phase cells. Moreover, a greater portion of sub-G1 apoptotic cells was observed in si-ZFX infected cells. CONCLUSIONS: These results strongly suggest that ZFX is a novel proliferation regulator that promotes growth of Osteosarcoma cells, and downregulation of ZFX expression induces growth suppression of Saos-2 cells via arrested G0/G1 phase cell cycle and apoptosis pathways, thereby indicating that ZFX may serve as a new molecular target for Osteosarcoma tumor therapy.

Effect of hyperbaric oxygen on post-stroke depression.

BACKGROUND: In patients with post-stroke depression (PSD) in diabetes, the situation may be more complex, requiring simultaneous treatment of blood glucose, depressive symptoms, and neurological dysfunction. Hyperbaric oxygen (HBO) therapy can improve tissue oxygen content and improve the situation of ischemia and hypoxia, thus playing a role in protecting brain cells and restoring the function of brain cells. However, there are few studies on HBO therapy for patients with PSD. This study explores the clinical efficacy of such therapy for stroke complicated with depression and diabetes mellitus, and to provide reference and basis for clinical treatment and development through the application of relevant rating scales and laboratory test indicators. AIM: To evaluate the clinical effects of HBO therapy on patients with diabetes with PSD. METHODS: A total of 190 diabetic patients with PSD were randomly divided into observation and control groups (95 patients per group). The control group received escitalopram oxalate 10mg once a day for eight weeks. In addition, the ob-servation group was also given HBO therapy, once a day, five times a week, for eight weeks. The Montgomery Depression Rating Scale (MADRS), National Institutes of Health Stroke Scale (NIHSS), hypersensitive C-reactive protein, tumor necrosis factor (TNF)-α, and fasting glucose levels were compared. RESULTS: There were no significant differences in age, sex, or depression course between the groups (P > 0.05). After HBO treatment, MADRS scores in both groups decreased significantly (14.3 ± 5.2), and were significantly lower in the control group (18.1 ± 3.5). After HBO treatment, NIHSS scores in both groups decreased significantly, and scores in the observation group (12.2 ± 4.0) decreased more than in the control group (16.1 ± 3.4), the difference was statistically significant (P < 0.001). The levels of hypersensitive C-reactive protein and TNF-α in both groups were significantly decreased, and the observation group was significantly lower than the control group (P < 0.001). Fasting blood glucose levels in both groups decreased significantly, and those in the observation group decreased more (8.02 ± 1.10) than in the control group (9.26 ± 1.04), with statistical significance (t = -7.994, P < 0.001). CONCLUSION: HBO therapy can significantly improve depressive symptoms and neurological dysfunction in patients with PSD, and reduce the levels of hypersensitive C-reactive protein, TNF-α and fasting blood glucose.

Paraspinal approach for thoracolumbar fracture.

OBJECTIVE: To explore the advantages and indications of the paraspinal approach by anatomical study and clinical application. METHODS: The anatomical data and clinical practice of 27 cases were analyzed to explore the accurate approach between the paraspinal muscles and the structure of ambient tissues, as well as the results of clinical application of paraspinal approach. The operation time, blood loss, incision length, radiographic result (Cobb angle, height of anterior edge of the vertebrae) were compared with those in 24 cases treated by traditional approach. RESULTS: Complete exposure of the facets could be easily performed by identifying natural cleavage plane between the multifidus and longissimus muscles. The natural muscular cleavage was (1.47+/-0.23) cm lateral to the midline for females, and (1.64+/-0.35) cm for males at T(12) level. The distance was (3.3+/-0.6) cm lateral to the midline for females, and (3.7+/-1.0) cm for males at L(4) level. In paraspinal approach group, the operation time was (76.2+/-15.7) min, blood loss was (91.6+/-16.9) ml and incision length was (7.6+/-0.8) cm. In traditional approach group, the operation time was (121.4+/-19.6) min, blood loss was (218.7+/-32.3) ml and incision length was (17.4+/-2.1) cm. To compare paraspinal approach with traditional approach, the operation time, blood loss and incision length had statistical difference (P less than 0.05) and the radiographic result (Cobb angle, height of anterior edge of the vertebrae) had no statistical difference (P larger than 0.05). CONCLUSIONS: When the paraspinal approach is performed through natural cleavage plane between the multifidus and longissimus muscles, there are no wide muscular disinsertions, leaving the supraspinous and interspinous ligaments intact. The distance of natural cleavage to the midline is different at T(12) and L(4) planes. By this approach, the facet joints can be explored easily and completely, and a clear surgical field will be available for the placement of pedicle screws. As a minimally invasive approach, it can be widely used in thoracolumbar spine surgery.

[Role of Bone Marrow Cell Morphology Combined with Immunohistochemistry Examinations in the Diagnosis of Patients with Primary Bone Marrow Lymphoma].

OBJECTIVE: To explore the diagnostic value of bone marrow cell morphology combined with immunohistochemistry in patients with primary bone marrow lymphoma. METHODS: The clinical data of 23 patients with primary bone marrow lymphoma diagnosed in the First Affiliated Hospital of Xi'an Jiaotong University from January 2010 to December 2019 were collected. The characteristics of bone marrow aspiration, bone marrow biopsy and immunohistochemistry results were analyzed retrospectively, and the diagnostic value of bone marrow cell morphology combined with immunohistochemistry in primary bone marrow lymphoma were clarified. RESULTS: Most of primary bone marrow lymphoma was B-cell lymphoma, among which diffuse large B-cell lymphoma was the most common pathological type. Typical lymphoma cells could be found in all the patients. 78.26% of the patients could be diagnosed as lymphoma with pathological type, while 91.30% were diagnosed as lymphoma through combined with the bone marrow immunohistochemistry. CONCLUSION: Bone marrow cell morphology combined with immunohistochemistry shows very important diagnostic value in patients with primary bone marrow lymphoma.

Three-dimensional gait characteristics of patients after unilateral total knee arthroplasty.

ABSTRACT: The purpose of this study is to evaluate the gait characteristics of bilateral limbs after unilateral total knee arthroplasty (TKA) using three-dimensional (3D) dynamic capture technology.Forty-two patients who underwent TKA were selected from the Orthopedic Medical Center of The Second Hospital of Jilin University from November 2018 to May 2019. We used a 3D dynamic capture system to measure the gait characteristics of patients at 3 months after TKA. The data, including relative position and direction of different body parts, the force between feet and ground, spatial and temporal relationship of the lower limb muscles, were measured. Besides, the surface electromyogram signal and the force plate analog signal were also collected. The walking ability, knee 3D kinematic, and kinetic characteristics were analyzed by the Cortex software.Spatial and temporal parameters, including stride frequency, double support phase, single support phase, step length, step time, step width, stride length, gait cycle, velocity, were no significant difference in bilateral lower extremities (P > .05). The reaction force of hip, knee, and ankle joint in the operation side were less than that of the healthy side, but the difference was not statistically significant (P > .05). However, when compared with the healthy side, the hip joint in operation side had a larger maximum extension angle (P < .001), the knee joint in operation side had a larger maximum valgus angle and valgus activity (P < .05), and had a smaller tibial maximum internal rotation angle (P < .05). Besides, the surface electromyogram signals of tibialis anterior muscles were reduced (P < .05).3D gait analysis, as an objective and quantitative evaluation method, is a safe, effective, and reliable method for evaluating postoperative knee function. The data of gait analysis prove that TKA is a vital treatment to improve the function of patients with knee arthritis. Besides, gait analysis also showed that there were various kinematic and biomechanical abnormalities in the knee after TKA, which may be the reason why the surgical knee could not immediately return to normal level.

Pedicle screw placement in the thoracic spine: a randomized comparison study of computer-assisted navigation and conventional techniques.

OBJECTIVE: To evaluate the accuracy of computer-assisted pedicle screw installation and its clinical benefit as compared with conventional pedicle screw installation techniques. METHODS: Total 176 thoracic pedicle screws placed in 42 thoracic fracture patients were involved in the study randomly, 20 patients under conventional fluoroscopic control (84 screws) and 22 patients had screw insertion under three dimensional (3D) computer-assisted navigation (92 screws). The 2 groups were compared for accuracy of screw placement, time for screw insertion by postoperative thin-cut CT scans and statistical analysis by X(2) test. The cortical perforations were then graded by 2-mm increments: Grade I (good, no cortical perforation), Grade II (screw outside the pedicle less than 2 mm), Grade III (screw outside the pedicle larger than 2 mm). RESULTS: In computer assisted group, 88 (95.65%) were Grade I (good), 4 (4.35%) were Grade II (less than 2mm), no Grade III (larger than 2 mm) violations. In conventional group, there were 14 cortical violations (16.67%), 70 (83.33%) were Grade I (good), 11 (13.1%) were Grade II (less than 2 mm), and 3 (3.57%) were Grade III (larger than 2 mm) violations (P less than 0.001). The number (19.57%) of upper thoracic pedicle screws ( T(1)-T(4) ) inserted under 3D computer-assisted navigation was significantly higher than that (3.57%) by conventional fluoroscopic control (P less than 0.001). Average screw insertion time in conventional group was (4.56+/-1.03) min and (2.54+/-0.63) min in computer assisted group (P less than 0.001). In the conventional group, one patient had pleura injury and one had a minor dura violation. CONCLUSIONS: This study provides further evidence that 3D computer-assisted navigation placement of pedicle screws can increase accuracy, reduce surgical time, and be performed safely and effectively at all levels of the thoracic spine, particularly upper thoracic spine.

A meta-analysis comparing regorafenib with TAS-102 for treating refractory metastatic colorectal cancer.

OBJECTIVE: We performed this meta-analysis to compare the efficacy and toxicity of regorafenib and TAS-102. METHODS: Electronic databases were searched to identify studies comparing the efficacy and safety of regorafenib and TAS-102 in patients with chemotherapy-refractory metastatic colorectal cancer using pooled analyses. RESULTS: Three clinical trials were included in this analysis. Regarding the reasons for treatment discontinuation, regorafenib was significantly associated with disease progression (odds ratio [OR] = 0.33, 95% confidence interval [CI] = 0.21-0.50) and adverse events (OR = 4.38, 95% CI = 2.69-7.13). However, overall (OR = 0.97, 95% CI = 0.81-1.17) and progression-free survival (OR = 1.01, 95% CI = 0.86-1.18) did not significantly differ between the groups. The most common treatment-related adverse events in the regorafenib group were neutropenia (OR = 0.06, 95% CI = 0.03-0.11), hand-foot syndrome (OR = 50.34, 95% CI = 10.44-242.84), and liver dysfunction (OR = 34.51, 95% CI = 8.30-143.43). Conversely, the incidence of thrombocytopenia did not differ between the two groups. CONCLUSIONS: Regorafenib and TAS-102 have similar efficacy but different adverse event profiles. Differences in the toxicity profiles of the two drugs will help guide treatment selection.