Design strategy and preliminary antiproliferative investigation of a modified lignan skeleton derived from aryne and statin.

The biological activities of natural products (NPs) provided precious resources for the development of new drugs. Numerous studies have shown that statins exhibit cytotoxic potential, which is now an extensive focus of investigation. Herein, a remarkably efficient method for modification of statins using hexadehydro-Diels-Alder (HDDA) arynes has been described. Notably, lactone, as the biologically active group of statins, was removed during the reaction and a novel modified lignan skeleton was generated via the Alder-ene process. Unexpectedly, these statin-derived novel chemical scaffolds exhibited moderate inhibition effects on the proliferation of cancer cells as determined by CCK-8 assays, and the IC50 values were in the micromolar range.

Anal canal duplication with heterotopic gastric mucosa and anal stenosis: first case report and literature review.

Introduction: Anal canal duplication (ACD) is a rare entity of gastrointestinal duplication that may be asymptomatic or present complications, such as abscess, fistulae, or malignant changes. The diagnosis and rational management of ACD still need to be clarified. Case presentation: We present a case of an 18-month-old girl with intractable perianal erosion and painful bowel movements for one year, and chronic constipation for six months. Fistulography revealed a tubular structure (3 cm in length), located posterior to the native anal canal. Mucosectomy was performed through a perineal approach combined with a coccigeal approach, and the postoperative course was uneventful. The pathological findings confirmed the diagnosis of ACD with heterotopic gastric mucosa, a rare combination that has not been described in the literature before. A literature search was conducted on the Medline database for studies reporting ACD in children. The study pool consisted of 77 cases of ACD from 32 studies, including the present case. According to our case report and in line with the literature, 43 cases (55.84%) were incidentally found; the most frequent symptom was constipation (14.29%), followed by painful anal mass or sacral pain (10.39%), and recurrent fistula (7.79%). Coexisting diseases were observed in 31 patients (40.26%), including 19 (24.68%) cases associated with presacral masses. Surgical management was employed in 73 patients (94.81%). ACD excision was performed in 47 patients (64.38%), combined with presacral mass resection or coccygectomy in 19 cases (26.03%). Conclusion: Preoperative imaging, including fistulography, ultrasonography, and magnetic resonance imaging, can provide useful information, especially for screening its associated anomalies. To prevent potential complications, surgical removal of ACD and associated anomalies is recommended. Mucosectomy may be one of the most effective surgical options for ACD due to its excellent functional outcome.

Influence of initial stresses and stress paths on the deformation and failure mechanism of sandy slate.

Rocks exhibit various mechanical properties under different stress conditions, with changes during unloading having significant implications for geological engineering safety. This study carried out triaxial loading and unloading mechanical tests on sandy slate to investigate its mechanical properties, deformation characteristics, and failure mechanisms at different initial stress levels and stress paths. The results showed that during the unloading process, the deformation modulus (E) of the sandy slate decreased, and the Poisson's ratio (µ) gradually increased. This indicates that significant volume expansion of the rock is the dominant factor in its deformation and failure. The exponential function can be used to describe the evolution of E and µ with confining pressure during unloading. The damage stress of the rock under unloading conditions was lower than that under loading conditions, suggesting that unloading led to an earlier onset of volumetric expansion in the sandy slate. Under conditions where the initial axial stress level approached the damage stress, the mechanical properties were most significantly affected by unloading. Compared to loading conditions, when the initial axial stress level was at 70% of the peak strength, the cohesion (c) decreased by 15.77 to 29.37%, while the internal friction angle (φ) increased by 1.88 to 5.14%. The rock's failure process can be divided into four stages based on the development of microcracks. Unloading during the stages of microcrack initiation and propagation can lead to tensile cracks of varying degrees, resulting in different mechanical properties and failure characteristics under loading and unloading conditions.

Early identification of hepatocellular carcinoma patients at high-risk of recurrence using the ADV score: a multicenter retrospective study.

BACKGROUND: Postoperative recurrence is a vital reason for poor 5-year overall survival in hepatocellular carcinoma (HCC) patients. The ADV score is considered a parameter that can quantify HCC aggressiveness. This study aimed to identify HCC patients at high-risk of recurrence early using the ADV score. METHODS: The medical data of consecutive HCC patients undergoing hepatectomy from The First Affiliated Hospital of Nanjing Medical University (TFAHNJMU) and Nanjing Drum Tower Hospital (NJDTH) were retrospectively reviewed. Based on the status of microvascular invasion and the Edmondson-Steiner grade, HCC patients were divided into three groups: low-risk group (group 1: no risk factor exists), medium-risk group (group 2: one risk factor exists), and high-risk group (group 3: coexistence of two risk factors). In the training cohort (TFAHNJMU), the R package nnet was used to establish a multi-categorical unordered logistic regression model based on the ADV score to predict three risk groups. The Welch's T-test was used to compare differences in clinical variables in three predicted risk groups. NJDTH served as an external validation center. At last, the confusion matrix was developed using the R package caret to evaluate the diagnostic performance of the model. RESULTS: 350 and 405 patients from TFAHNJMU and NJDTH were included. HCC patients in different risk groups had significantly different liver function and inflammation levels. Density maps demonstrated that the ADV score could best differentiate between the three risk groups. The probability curve was plotted according to the predicted results of the multi-categorical unordered logistic regression model, and the best cut-off values of the ADV score were as follows: low-risk ≤ 3.4 log, 3.4 log < medium-risk ≤ 5.7 log, and high-risk > 5.7 log. The sensitivities of the ADV score predicting the high-risk group (group 3) were 70.2% (99/141) and 78.8% (63/80) in the training and external validation cohort, respectively. CONCLUSION: The ADV score might become a valuable marker for screening patients at high-risk of HCC recurrence with a cut-off value of 5.7 log, which might help surgeons, pathologists, and HCC patients make appropriate clinical decisions.

Research progress of protein induced by vitamin K absence or antagonist II in liver transplantation for hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is the most common pathologic type of primary liver cancer. Liver transplantation (LT) is a radical strategy for treating patients with early-stage HCC, which may lead to a better prognosis compared to hepatectomy and ablation. However, survival of patients who develop HCC recurrence after LT is short, and early recurrence is the most common cause of death. Thus, efficient biomarkers are also needed in LT to guide precision therapy to improve patient prognosis and 5-year survival. Protein induced by vitamin K absence or antagonist II (PIVKA-II) is an abnormal prothrombin that cannot activate coagulation, and it is significantly increased in patients with HCC, obstructive jaundice, and those taking vitamin K antagonists. Over the past decades, substantial progress has been made in the study of PIVKA-II in diagnosing, surveilling, and treating HCC, but its role in LT still needs to be elaborated. In this review, we focused on the role of PIVKA-II as a biomarker in LT for HCC, especially its relationship with clinicopathologic features, early recurrence, long-term survival, and donor-recipient selection.

Radiomic Features at Contrast-Enhanced CT Predict Virus-Driven Liver Fibrosis: A Multi-Institutional Study.

INTRODUCTION: Liver fibrosis is a major cause of morbidity and mortality among in patients with chronic hepatitis. Radiomics, particularly of the spleen, may improve diagnostic accuracy and treatment strategies. External validations are necessary to ensure reliability and generalizability. METHODS: In this retrospective study, we developed 3 radiomics models using contrast-enhanced computed tomography scans from 167 patients with liver fibrosis (training group) between January 2020 and December 2021. Radiomic features were extracted from arterial venous, portal venous, and equilibrium phase images. Recursive feature selection random forest and the least absolute shrinkage and selection operator logistic regression were used for feature selection and dimensionality reduction. Performance was assessed by area under the curve, C-index, calibration plots, and decision curve analysis. External validation was performed on 114 patients from 2 institutions. RESULTS: Twenty-five radiomic features were significantly associated with fibrosis stage, with 80% of the top 10 features originating from portal venous phase spleen images. The radiomics models showed good performance in the validation cohort (C-indices 0.723-0.808) and excellent calibration. Decision curve analysis indicated clinical benefits, with machine learning-based radiomics models (Random Forest score and support vector machine based radiomics score) providing more significant advantages. DISCUSSION: Radiomic features offer significant benefits over existing serum indices for staging virus-driven liver fibrosis, underscoring the value of radiomics in enhancing diagnostic accuracy. Specifically, radiomics analysis of the spleen presents additional noninvasive options for assessing fibrosis, highlighting its potential in improving patient management and outcomes.

Erratum: Linc-KILH potentiates Notch1 signaling through inhibiting KRT19 phosphorylation and promotes the malignancy of hepatocellular carcinoma: Erratum.

[This corrects the article DOI: 10.7150/ijbs.52279.].

Construction of an Electron Capture and Transfer Center for Highly Efficient and Selective Solar-Light-Driven CO2 Conversion.

Exploring high-efficiency photocatalysts for selective CO2 reduction is still challenging because of the limited charge separation and surface reactions. In this study, a noble-metal-free metallic VSe2 nanosheet was incorporated on g-C3N4 to serve as an electron capture and transfer center, activating surface active sites for highly efficient and selective CO2 photoreduction. Quasi in situ X-ray photoelectron spectroscopy (XPS), soft X-ray absorption spectroscopy (sXAS), and femtosecond transient absorption spectroscopy (fs-TAS) unveiled that VSe2 could capture electrons, which are further transferred to the surface for activating active sites. In situ diffuse reflectance infrared Fourier transform spectroscopy (DRIFTS) and density functional theory (DFT) calculations revealed a kinetically feasible process for the formation of a key intermediate and confirmed the favorable production of CO on the VSe2/PCN (protonated C3N4) photocatalyst. As an outcome, the optimized VSe2/PCN composite achieved 97% selectivity for solar-light-driven CO2 conversion to CO with a high rate of 16.3 µmol·g-1·h-1, without any sacrificial reagent or photosensitizer. This work offers new insights into the photocatalyst design toward highly efficient and selective CO2 conversion.

Assessing the impact of dust events on the Holiday Climate Index in the Taklimakan Desert region.

As a significant sector within the tourism industry, desert tourism has developed rapidly in recent years, contributing significantly to local economic development. On the other hand, desert tourism is constantly influenced by the desert climate, characterized by high temperatures, aridity, and dust events. This study examines and analyzes the impact of dust events on the Holiday Climate Index (HCI) using an improved methodology. It incorporates comprehensive meteorological data including temperature, relative humidity, cloud cover, precipitation, wind speed and dust events of Tazhong, located in the heart of the Taklimakan Desert. The results indicate that the maximum mean monthly HCI dips from an ideal level (91) to a very good level (73), the minimum dips from good level (66) to a marginal level (47), and the annual comfortable days (HCI ≥ 80) decrease from 180.5 to 95.3 after considering the impacts of dust events. The corrective HCI indicates that autumn, especially October, offers relatively comfortable climatic conditions for tourism, with the mean monthly comfortable days reach 20.1. These findings can better guide desert tourism activities and also demonstrate that the impact of dust weather on tourism activities cannot be ignored.

Clinical evaluation of a new COVID-19 antigen rapid test kit for detection of SARS-CoV-2.

The antigen rapid diagnostic test (Ag-RDT) is an assay kit for detecting the SARS-COV-2 nucleocapsid proteins, based on the colloidal gold method.Accurate diagnosis has an important role in limiting the transmission of SARS-COV-2, and also helps patients to receive earlier treatment .The object of this study was to perform the clinical evaluation of a novel Ag-RDTs with samples collected from two different swabs.DEEPBLUE®COVID-19 antigen detection kit used for the examination of the subjects in the experiment.For antigen testing on samples collected with nasal swabs, sensitivity was 91.7 % (95 % CI 83.6-96.6 %) and specificity was 100 %(95 %CI 98.1-100 %).For nasopharyngeal swabs, the sensitivity was 96.8 % (95 % CI 93.6-98.7 %) and the specificity was 100 % (95 % CI 98.2-100 %).Fisher Precision test showed a significant correlation between nasopharyngeal swab Ag-RDTs and nasal swab Ag-RDTs and RT-qPCR test (p-value <0.001).The results showed that the patients use the kit for testing were comparable to the RT-qPCR.

Toddler with giant omental cyst, profound anemia, and shock: case report and review of the literature.

Giant greater omental cysts with associated massive hemorrhage are rare. We encountered a 16-month-old boy with a four-day history of acute abdominal pain, distension, and paleness. Physical examination revealed a blood pressure of 74/27 mmHg. No well-defined masses were observed on abdominal palpation. The hemoglobin level on admission was 24 g/L. After initial resuscitation and blood transfusion, a computed tomography (CT) scan was performed, revealing a giant cystic mass with an intracystic hemorrhage. The diagnosis was confirmed via exploratory laparotomy, and the cyst, with the attached partial omentum was removed. Pathological findings revealed a simple cyst originating from the greater omentum. The patient recovered uneventfully and remained well during the two-year follow-up period. We reviewed the literature published over the last 27 years on cases of omental cysts to evaluate demographic characteristics, clinical presentations, complications, diagnostic tool options, and surgical approaches.

A Novel Nomogram for the Preoperative Prediction of Edmondson-Steiner Grade III-IV in Hepatocellular Carcinoma Patients.

Background: Edmondson-Steiner (E-S) grade is a pathological indicator of the degree of hepatocellular carcinoma (HCC) differentiation, and E-S grade III-IV is a poor prognostic factor for HCC patients. Predicting poorly differentiated HCC has essential significance for clinical decision-making. Although some studies have developed predictive models based on magnetic resonance imaging (MRI) and radiomics, radiomic features that require specific software for analysis are impractical for clinical work. This study aims to develop a novel and user-friendly nomogram model to predict E-S grade III-IV. Patients and Methods: Medical data on patients meeting the inclusion criteria were obtained from the Nanjing Drum Tower Hospital HCC database (January 2020 to December 2022). Univariate analysis was used to screen for risk factors associated with E-S grade III-IV. A novel nomogram was established based on the subsequent multivariate logistic regression analysis. The performance of the established model was evaluated through diagnostic ability, calibration, and clinical benefits. Results: Overall, 240 HCC patients were included in this study. Among them, 103 were highly differentiated (E-S grade I-II) HCC and 137 were poorly differentiated (E-S grade III-IV) HCC. A nomogram model that integrated alpha-fetoprotein (AFP), des-γ-carboxy prothrombin (DCP), hepatitis B virus surface antigen (HBsAg), hepatitis C virus antibodies (HCVAb), aspartate aminotransferase to lymphocyte ratio index (ALRI), and macrovascular invasion was established. The novel model had a good diagnostic performance with an area under the curve (AUC) value of 0.763. Meanwhile, the model had a diagnostic accuracy of 72.5%, a sensitivity of 78.1%, and a specificity of 65.1%. The calibration curve showed good calibration of the nomogram model (mean absolute error = 0.043), and the decision curve analysis (DCA) demonstrated that the clinical benefit was provided. Conclusion: Our developed nomogram model could successfully predict E-S grade III-IV in HCC patients, which may be helpful in clinical decision-making.

A decision tree model to predict liver cirrhosis in hepatocellular carcinoma patients: a retrospective study.

Background: The severity of liver cirrhosis in hepatocellular carcinoma (HCC) patients is essential for determining the scope of surgical resection. It also affects the long-term efficacy of systemic anti-tumor therapy and transcatheter arterial chemoembolization (TACE). Non-invasive tools, including aspartate aminotransferase to platelet ratio index (APRI), fibrosis-4 (FIB-4), and γ-glutamyl transferase to platelet ratio (GPR), are less accurate in predicting cirrhosis in HCC patients. We aimed to build a novel decision tree model to improve diagnostic accuracy of liver cirrhosis. Patients and Methods: The Mann-Whitney U test, χ2 test, and multivariate logistic regression analysis were used to identify independent cirrhosis predictors. A decision tree model was developed using machine learning algorithms in a training cohort of 141 HCC patients. Internal validation was conducted in 99 HCC patients. The diagnostic accuracy and calibration of the established model were evaluated using receiver operating characteristic (ROC) and calibration curves, respectively. Results: Sex and platelet count were identified as independent cirrhosis predictors. A decision tree model integrating imaging-reported cirrhosis, APRI, FIB-4, and GPR was established. The novel model had an excellent diagnostic performance in the training and validation cohorts, with area under the curve (AUC) values of 0.853 and 0.817, respectively. Calibration curves and the Hosmer-Lemeshow test showed good calibration of the novel model. The decision curve analysis (DCA) indicated that the decision tree model could provide a larger net benefit to predict liver cirrhosis. Conclusion: Our developed decision tree model could successfully predict liver cirrhosis in HCC patients, which may be helpful in clinical decision-making.

Circular RNA in cholangiocarcinoma: A systematic review and bibliometric analysis.

BACKGROUND: Cholangiocarcinoma (CCA) is a common primary liver malignancy with a poor prognosis. Many studies have demonstrated the involvement of circular RNAs (circRNAs) in tumorigenesis and progression. METHODS: Four online databases (PubMed, Web of Science, Embase, and Scopus) were searched on May 04, 2023, for original papers regarding CCA and circRNAs. Bibliometric analysis of included studies was performed on R Studio and GraphPad Prism. RESULTS: Thirty studies were included in the systematic review and bibliometric analysis. The systematic review showed that circRNAs were involved in CCA proliferation, invasion, metastasis, chemotherapy resistance, and other biological processes and were related to the prognosis of patients and many clinicopathological features. Exosomal circRNAs provide a new idea for the early diagnosis of CCA. The bibliometric analysis showed a significant upward trend in the number of studies on CCA and circRNAs. The 30 included papers had 201 authors and were published in 22 English journals. The first paper was published in 2018, and the second paper was the most cited (148 citations). CONCLUSION: This systematic review and bibliometric analysis demonstrates that circRNAs in CCA have not been studied enough. CircRNAs play an important role in the occurrence and progression of CCA. They may become new targets for the diagnosis, treatment, and prognostic monitoring of CCA.

The value of RACK1 and peripheral blood M2/M1 monocyte ratio on the prognosis of patients with oral squamous cell carcinoma.

This study is to evaluate the effect of receptor for activated c kinase 1 (RACK1) and peripheral blood M2/M1 monocytes ratio on the prognosis of patients with oral squamous cell carcinoma (OSCC). A total of 115 OSCC patients who underwent radical surgery in North China University of Science and Technology Affiliated Hospital from January 2015 to December 2015 were included in the experimental group and 34 healthy individuals after a physical examination during the same period were included in the control group. Cancer and para-cancerous tissues were collected and the relationship between RACK1 and M2/M1 ratio and the prognosis of OSCC patients and its predictive value were analyzed. RACK1, M2/M1 ratio, clinical stages, lymphatic metastasis, recurrence and metastasis were considered independent factors for the prognosis of OSCC patients (p<0.05); In addition, RACK1 and the M2/M1 ratio were proven to be of significant predictive values for the prognosis of OSCC patients (p<0.05). RACK1 and peripheral blood M2/M1 monocytes ratio demonstrate great potential as prognostic predictors of OSCC patients.

Liquid Biopsy in Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is one of the most deadly neoplasms with a poor prognosis. Due to the significant tumor heterogeneity of HCC, alpha-fetoprotein (AFP) or liver biopsy has not yet met the clinical needs in terms of early diagnosis or determining prognosis. In recent years, liquid biopsy techniques that analyze tumor by-products released into the circulation have shown great potential. Its ability to monitor tumors in real time and respond to their global characteristics is expected to improve the management of HCC patients clinically. This review discusses some of the findings of a liquid biopsy in terms of diagnosis and prognosis of HCC.

The XOR-IDH3α axis controls macrophage polarization in hepatocellular carcinoma.

BACKGROUND & AIMS: Tumor-associated macrophages (TAMs) are indispensable in the hepatocellular carcinoma (HCC) tumor microenvironment. Xanthine oxidoreductase (XOR), also known as xanthine dehydrogenase (XDH), participates in purine metabolism, uric acid production, and macrophage polarization to a pro-inflammatory phenotype. However, the role of XOR in HCC-associated TAMs is unclear. METHODS: We evaluated the XOR level in macrophages isolated from HCC tissues and paired adjacent tissues. We established diethylnitrosamine/carbon tetrachloride (CCl4)-induced and orthotopically implanted HCC mouse models using mice with Xdh-specific depletion in the myeloid cell lineage (Xdhf/fLyz2cre) or Kupffer cells (Xdhf/fClec4fcre). We determined metabolic differences using specific methodologies, including metabolomics and metabolic flux. RESULTS: We found that XOR expression was downregulated in HCC TAMs and positively correlated with patient survival, which was strongly related to the characteristics of the tumor microenvironment, especially hypoxia. Using HCC-inflicted mice (Xdhf/fLyz2cre and Xdhf/fClec4fcre), we revealed that XOR loss in monocyte-derived TAMs rather than Kupffer cells promoted their M2 polarization and CD8+ T-cell exhaustion, which exacerbated HCC progression. In addition, the tricarboxylic acid cycle was disturbed, and the generation of α-ketoglutarate was enhanced within XOR-depleted macrophages. XOR inhibited α-ketoglutarate production by interacting with IDH3α catalytic sites (K142 and Q139). The increased IDH3α activity caused increased adenosine and kynurenic acid production in TAMs, which enhanced the immunosuppressive effects of TAMs and CD8+ T cells. CONCLUSIONS: The XOR-IDH3α axis mediates TAM polarization and HCC progression and may be a small-molecule therapeutic or immunotherapeutic target against suppressive HCC TAMs. IMPACT AND IMPLICATIONS: Immunotherapies have been widely applied to the treatment of hepatocellular carcinoma (HCC), but to date they have been associated with unsatisfactory efficacy. The tumor microenvironment of HCC is full of different infiltrating immune cells. Tumor-associated macrophages (TAMs) are vital components in the tumor microenvironment and are involved in HCC progression. Herein, we confirm the downregulation of XOR expression in TAMs isolated from human HCC. The loss of XOR in monocyte-derived macrophages increases IDH3 activity and results in an increase in α-ketoglutarate production, which can promote M2-like polarization. Additionally, XOR-null TAMs derived from monocytes promote CD8+ T-cell exhaustion via the upregulation of immunosuppressive metabolites, including adenosine and kynurenic acid. Given the prevalence and high rate of incidence of HCC and the need for improved therapeutic options for patients, our findings identify potential therapeutic targets that may be further studied to develop improved therapies.

Three-Dimensional Macroporous rGO-Aerogel-Based Composite Phase-Change Materials with High Thermal Storage Capacity and Enhanced Thermal Conductivity.

Three-dimensional porous network encapsulation strategy is an effective means to obtain composite phase-change materials (PCMs) with high heat storage capacity and enhanced thermal conductivity. Herein, macroporous reduced graphene oxide (rGO) aerogels with adjustable pore size are prepared by the emulsion template method and hydrothermal reduction process. Further, the shape-stabilized rGO-aerogel-based composite PCMs are constructed after the combination of 3D porous rGO supports and paraffin wax (PW) through vacuum melting infiltration. By regulating the pore structure of the rGO aerogel network, the rGO-based composite PCMs achieve excellent energy storage properties with a phase-change enthalpy of 179.94 J/g for the loading amount of 95.61 wt% and an obvious enhancement in thermal conductivity of 0.412 W/m-1·K-1, which is 54.89% higher than pristine PW and enduring thermal cycling stability. The obtained macroporous rGO-aerogel-based composite PCMs with high thermal storage and heat transfer performance effectively broaden the application of PCMs in the field of thermal energy storage.

Conversion therapy for massive hepatocellular carcinoma: A case report and literature review.

Key Clinical Message: For potentially resectable HCC, a more aggressive conversion therapy strategy (high-intensity combined with multiple treatment modalities) can be used. Abstract: Hepatocellular carcinoma (HCC) is the sixth most common malignancy worldwide. The best treatment for HCC is radical surgical resection, but 70%-80% of patients are ineligible for surgery. Although conversion therapy is an established treatment strategy for various solid tumors, there is no uniform protocol for treating HCC. In this case, we present a 69-year-old male patient diagnosed with massive HCC with Barcelona clinical liver cancer (BCLC) stage B. Because of the insufficient volume of the future liver remnant, we believed radical surgical resection was temporarily impossible. Therefore, the patient received conversion therapy, including four cycles of transcatheter arterial embolization (TAE) and hepatic arterial infusion chemotherapy (HAIC-Folfox), lenvatinib (8 mg orally once a day), and tislelizumab (an anti-PD-1 antibody, 200 mg intravenously once every 3 weeks). Fortunately, the patient achieved a good treatment response (smaller lesions and improved liver function) and underwent radical surgery finally. There was no clinical evidence of recurrence at 6 months of follow-up. For potentially resectable HCC, this case reveals that a more aggressive conversion therapy strategy (high-intensity combined with multiple treatment modalities) can be used.

Study on the mechanical properties of unloading damaged sandstone under cyclic loading and unloading.

To reveal the mechanical properties of rocks under stress disturbance and unloading confining pressure, conventional triaxial compression tests, triaxial compression tests on unloading damaged sandstone, and cyclic loading and unloading tests on unloading damaged sandstone were conducted. Then, the evolutionary characteristics of dissipated energy in sandstone under cyclic loading and unloading were explored, and damage variables were proposed. The crack development characteristics were analyzed from a microscopic perspective. The study results reveal that: (1) the sandstone exhibits obvious brittle failure under different stress paths, and the macroscopic failure mode is dominated by shear failure. As the number of cycles increases, the load-bearing capacity, elastic modulus, and deformation modulus of the sandstone will be significantly reduced if it suffers greater unloading damage. (2) The cyclic action in the early stage inhibits the development of the internal fracture. However, the inhibitory effect is significantly reduced for specimens with larger unloading quantities. The damage variable in the cyclic loading and unloading is about 50.00% of that in the unloading, indicating that unloading confining pressure is the dominant factor for specimen failure. (3) The extension of microcracks within the sandstone is dominated by intergranular cracks, and the number of cracks increases with the increase of unloading quantity. After cyclic loading and unloading, the structure becomes looser. The test results deepen the understanding of rock mechanical behavior and fracture evolution under cyclic loading and can provide a basis for structural stability improvement under stress disturbance and unloading confining pressure.