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BackgroundThis study conducts a systematic review through meta-analysis, comparing the composition and diversity of the gut microbiome in patients with esophageal cancer and healthy individuals, and explores the relationship between risk factors and related factors of esophageal cancer.MethodsAccording to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA), we comprehensively searched the databases of PubMed, Web of Science, Embase, Cochrane Library. In addition, we applied the R programming language version 4.0.3 and Stata 15.1 software for data analysis. We also implemented the Newcastle-Ottawa Scale (NOS), funnel plot analysis, Egger’s test, and Begg’s test to assess the risk of bias.ResultsIn this study, a total of 328 studies were identified through the literature search. Among them, 117 duplicate studies were removed, and 202 studies were excluded based on inclusion and exclusion criteria. Finally, 9 studies were included in the analysis, involving a total of 216 patients with esophageal carcinoma and 352 healthy controls. Four studies provided Chao1 index for quantitative consolidation (ES = 637.41, 95% CI: 549.16 to 725.66, p = 0.000, I2 = 98.2%). Two studies [27, 29] reported ACE index (ES = 438.89, 95% CI: 362.42 to 515.35, p = 0.000, I2 = 97%). Seven studies [26,27,29,30,32] reported the Shannon index for quantitative consolidation (ES = 4.38, 95% CI: 3.95 to 4.81, p = 0.000, I2 = 99%). At the phylum level, the abundance of Bacteroidetes(ES = 37.8, 95% CI: 25.75 to 49.85, p = 0.000, I2 = 87.2%) and Proteobacteria(ES = 7.48, 95% CI: 5.02 to 8.85, p = 0.04, I2 = 2.4%) have statistical difference between ESCC and HC. There was no significant difference between ESCC and HC in the abundance of genera(p>0.05).ConclusionsThis observational meta-analysis revealed that changes in the GM were correlated with esophageal carcinoma, and variations in some advantageous GM might involve regional differences. Additionally, the study aims to facilitate early diagnosis of esophageal cancer and improve screening and diagnostic efficiency.

BackgroundSolid pseudopapillary neoplasms of the pancreas with hepatic metastases are infrequent and difficult to diagnose, and treatment is uncertain.MethodsA retrospective analysis of clinical data from patients with pancreatic solid pseudopapillary neoplasm (SPN) hepatic metastases who underwent surgery at the First Hospital of Jilin University from January 2005 to December 2021 was conducted. A total of 287 patients with SPN were included in the study, of which 8 (3%) developed liver metastases, all of whom were treated surgically and recovered well after surgery. The clinical presentation, imaging features, surgical treatment, histopathological examination, and postoperative follow-up data (mean 70 months; range 28–138 months) of the patients were recorded and analyzed. Clinical response strategies can be derived by reviewing previous studies on hepatic metastases of SPNs.ResultsFor resectable hepatic metastases from pancreatic solid pseudopapillary neoplasms, early surgery with total resection of the primary tumor and metastasis has shown great efficiency and is associated with patient good prognosis. In patients presenting unresectable hepatic metastases, aggressive tumor reduction surgery resulted in the alleviation of clinical symptoms and reduction of tumor burden while potentially achieving long-term survival.ConclusionFor hepatic metastases of SPNs, a preoperative liver tissue biopsy is beneficial for a definitive diagnosis. Surgery demonstrates excellent therapeutic efficacy and is considered the preferred curative treatment approach. This paper presents clinical experiences with SPN-related hepatic metastases at the Affiliated Hospital of Jilin University, which can be used to guide patient counseling in clinical practice.

Lung cancer stands as a malignant neoplasm bearing the highest burden of morbidity and mortality within the elderly population on a global scale. Among the lung cancer subtypes, non-small cell lung cancer (NSCLC) prevails as the most prevalent. As age advances, elderly patients often present with an increased prevalence of comorbidities, diminished organ reserve function, and alterations in drug pharmacokinetics, including absorption, distribution, metabolism, and clearance. These factors collectively contribute to a reduction in their capacity to tolerate therapeutic interventions. Regrettably, there exists a paucity of research data and evidence regarding the management of elderly patients afflicted by advanced lung cancer. This article endeavors to compile and elucidate strategies for the enhancement of treatment approaches, with the aim of aiding clinical decision-making. Prior to the selection of clinical treatment modalities for elderly patients with advanced NSCLC, a comprehensive assessment should be conducted, taking into account various facets, including tumor characteristics, patient age, physiological status, and the presence of comorbidities. The treatment strategy should be implemented in a tiered fashion, thereby affording the opportunity for the tailoring of individualized therapeutic approaches for elderly patients afflicted by advanced NSCLC. The demographic of elderly patients confronting advanced NSCLC presents a complex landscape marked by intricate underlying conditions, necessitating the imperative optimization of treatment strategies.

BackgroundOur study aimed to develop a nomogram incorporating cytokeratin fragment antigen 21–1 (CYFRA21–1) to assist in differentiating between patients with intrahepatic cholangiocarcinoma (ICC) and hepatocellular carcinoma (HCC).MethodsA total of 487 patients who were diagnosed with ICC and HCC at Qilu Hospital of Shandong University were included in this study. The patients were divided into a training cohort and a validation cohort based on whether the data collection was retrospective or prospective. Univariate and multivariate analyses were employed to select variables for the nomogram. The discrimination and calibration of the nomogram were evaluated using the area under the receiver operating characteristic curve (AUC) and calibration plots. Decision curve analysis (DCA) was used to assess the nomogram’s net benefits at various threshold probabilities.ResultsSix variables, including CYFRA21–1, were incorporated to establish the nomogram. Its satisfactory discriminative ability was indicated by the AUC (0.972 for the training cohort, 0.994 for the validation cohort), sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) values. The Hosmer–Lemeshow test and the calibration plots demonstrated favorable consistency between the nomogram predictions and the actual observations. Moreover, DCA revealed the clinical utility and superior discriminative ability of the nomogram compared to the model without CYFRA21–1 and the model consisting of the logarithm of alpha-fetoprotein (Log AFP) and the logarithm of carbohydrate antigen 19–9 (Log CA19–9). Additionally, the AUC values suggested that the discriminative ability of Log CYFRA21–1 was greater than that of the other variables used as diagnostic biomarkers.ConclusionsThis study developed and validated a nomogram including CYFRA21–1, which can aid clinicians in the differential diagnosis of ICC and HCC patients.

Phosphoinositide 3-kinase (PI3K) inhibitors have shown synergistic anticancer effects with endocrine therapy against ER+/PIK3CA-mutated breast cancer. PI3K inhibitors for cancer therapy are becoming more common. There is an increasing need to understand their cardiac adverse events. In this report, we describe the features of near-fatal mixed arrhythmias in a patient who was undergoing a phase Ib clinical study of PI3Kα inhibitor with fulvestrant. Subsequently, the patient survived by cardiopulmonary resuscitation and therefore did not die. This case highlights that PI3K inhibitors can induce QT/QTc prolongation and predispose patients to TdP. The combination of QT/QTc prolongation in combination with prolonged cardiac repolarization, such as an AV block during treatment with PI3Kα inhibitor, may aggravate the occurrence of TdP. It is likely to be a safer strategy to adjust the standard of discontinuing drugs and continuing drugs (QTc interval was

A 43-year-old woman with a history of uterine fibroids, anemia, and deep vein thrombosis presented with a chief symptom of prolapse of tumor from the perineum, complicated by infection. The case was further complicated by bilateral pulmonary multiple embolism, deep vein thrombosis, acute cardiac insufficiency, acute renal insufficiency, and shock. The patient was treated with preoperative placement of an inferior vena cava filter, open hysterectomy, and perioperative anticoagulation with low-molecular-weight heparin. She smoothly navigated the perioperative period and recovered completely.

BackgroundSolid pseudopapillary neoplasms (SPNs) of the pancreas are indolent rare tumors with malignant potential. The risk factors associated with the malignant behavior of SPNs are still unclear.MethodsA retrospective analysis of patients with SPNs who underwent surgical treatment in the First Hospital of Jilin University from January 2010 to January 2022 was conducted. The clinical baseline data, pathology, imaging, and laboratory indicators of the patients were analyzed by univariate and multivariate logistic regression to identify the independent risk factors associated with the high-risk groups, and a predictive model was established in the form of a nomogram.ResultsIn multivariate analysis, clinical symptoms (P < 0.001), unclear tumor margins (P = 0.001), incomplete tumor capsules (P = 0.005), maximum tumor diameters ≥ 7.2 cm (P = 0.003), and prognostic nutritional index values < 47.45 (P = 0.007) were independent risk factor for SPNs with high-risk groups. A nomogram model was successfully established to predict high-risk groups of SPNs. The area under the receiver operating characteristic curve was 0.856. The calibration prediction curve was in good agreement with the standard curve.ConclusionThe nomogram model based on clinical symptoms, inflammatory markers, and imaging features had a high application value in the preoperative prediction of the high-risk groups of SPNs. A novel nomogram of the affiliated hospital of Jilin University-SPNs risk model was proposed for routine application to guide the patient counseling in clinical practice.

PurposeThe objective of this study was to conduct a meta-analysis comparing the diagnostic efficacy of models based on diffusion-weighted imaging (DWI)-MRI, dynamic contrast enhancement (DCE)-MRI, and combination models (DCE and DWI) in distinguishing benign from malignant non-mass enhancement (NME) breast lesions.Materials and methodsPubMed, Embase, and Cochrane Library were searched, from inception to January 30, 2023, for studies that used DCE or DWI-MRI for the prediction of NME breast cancer patients. A bivariate random-effects model was used to calculate the meta-analytic sensitivity, specificity, and area under the curve (AUC) of the DCE, DWI, and combination models. Subgroup analysis and meta-regression analysis were performed to find the source of heterogeneity.ResultsOf the 838 articles screened, 18 were eligible for analysis (13 on DCE, five on DWI, and four studies reporting the diagnostic accuracy of both DCE and DWI). The funnel plot showed no publication bias (p > 0.5). The pooled sensitivity and specificity and the AUC of the DCE, DWI, and combination models were 0.58, 0.72, and 0.70, respectively; 0.84, 0.69, and 0.84, respectively; and 0.88, 0.79, 0.90, respectively. The meta-analysis found no evidence of a threshold effect and significant heterogeneity among trials in terms of DCE sensitivity and specificity, as well as DWI specificity alone (I2 > 75%). The meta-regression revealed that different diagnostic criteria contributed to the DCE study’s heterogeneity (p < 0.05). Different reference criteria significantly influenced the heterogeneity of the DWI model (p < 0.05). Subgroup analysis revealed that clustered ring enhancement (CRE) had the highest pooled specificity (0.92) among other DCE features. The apparent diffusion coefficient (ADC) with a mean threshold

BackgroundSince no randomized controlled trials have directly compared the efficacy and safety of immunotherapy with daratumumab versus lenalidomide/bortezomib/dexamethasone (RVD) in the frontline treatment of transplant-ineligible newly diagnosed multiple myeloma (TIE-NDMM), this study systematically reviewed the clinical studies regarding immunotherapy with daratumumab and RVD regimen in the treatment of TIE-NDMM to explore the optimization direction of the best first-line therapy.MethodsThe Cochrane Library, PubMed, Embase, and Web of Science databases were searched to collect studies on regimens containing daratumumab or RVD/RVD-lite for TIE-NDMM. Pooled and meta-analysis was then performed to compare the overall response rate (ORR), stringent complete remission (sCR) and CR rate, progression-free survival (PFS), overall survival (OS) and treatment-related discontinuation rate between daratumumab-containing immunotherapy regimen and RVD/RVD-lite regimen by using R 4.3.1 software.ResultsNine prospective clinical trials were included, including 1795 TIE-NDMM or NDMM without intent for immediate ASCT. Among them, 938 patients were treated with daratumumab-based immunotherapy and 857 with RVD/RVD-lite regimens. Meta-analysis results showed that The daratumumab-based regimen showed a significantly higher CR/sCR rate than RVD/RVD-lite for TIE-NDMM (47% vs. 24%, P

BackgroundThe molecular classification of endometrial cancer has previously been shown to be associated with clinical outcomes. However, there are insufficient data to support the routine use of molecular classification for the treatment of patients seeking fertility preservation.MethodsHere, we retrospectively investigated 90 patients received fertility-sparing treatment. We used a next generation sequencing (NGS) panel to classify these patients into four subtypes. All patients received hormonal therapy combined with hysteroscopy. Therapeutic effects were evaluated by hysteroscopy every three months during the treatment.ResultsPatients with POLE mutations had the highest disease progression rate (50.0%, P=0.013), while the microsatellite instability-high (MSI-H) group had the highest recurrence rate (50.0%, P=0.042). PIK3CA mutation (hazard ratio (HR): 0.61; 95% confidence interval (CI): 0.37–0.99; P=0.046), overweight (HR: 0.56; 95% CI: 0.32–0.96; P=0.033) and obesity (HR: 0.44; 95% CI: 0.20–0.95; P=0.036) were associated with a significantly lower cumulative complete response (CR) rate. The combination of gonadotropin-releasing hormone analogues (GnRH-a) and letrozole (HR: 3.43; 95% CI: 1.81–6.52; P< 0.001) was associated with a significantly higher cumulative CR rate. KRAS mutation was significantly associated with disease progression (P=0.002). In wild-type TP53 patients, PTEN and PIK3CA mutations significantly prolonged the duration of treatment to achieve CR (log rank P=0.034; P=0.018).ConclusionThe implementation of molecular classification for EC patients undergoing fertility-sparing treatment is promising and can facilitate the selection of appropriate medical regimes to achieve better outcomes in patients with EC who require fertility preservation treatment.

ObjectivesDue to the increase in life expectancy and the aging of the global population, the “Belt and Road” (“B&R”) countries are faced with varying degrees of lung cancer threat. The purpose of this study is to analyze the differences in the burden and trend of lung cancer disability in the “B&R” countries from 1990 to 2019 so as to provide an analytical strategic basis to build a healthy “B&R”.MethodsData were derived from the Global Burden of Disease 2019 (GBD 2019). Incidence, mortality, prevalence, the years lived with disability (YLDs), and disability-adjusted life years (DALYs) of lung cancer and those attributable to different risk factors were measured from 1990 to 2019. Trends of disease burden were estimated by using the average annual percent change (AAPC), and the 95% uncertainty interval (UI) was reported.ResultsChina, India, and the Russian Federation were the three countries with the highest burden of lung cancer in 2019. From 1990 to 2019, the AAPC of incidence, prevalence, mortality, and DALYs generally showed a downward trend in Central Asia (except Georgia) and Eastern Europe, while in China, South Asia (except Bangladesh), most countries in North Africa, and the Middle East, the trend was mainly upward. The AAPC of age-standardized incidence was 1.33% (1.15%–1.50%); the AAPC of prevalence, mortality, and DALYs from lung cancer in China increased by 24% (2.10%–2.38%), 0.94% (0.74%–1.14%), and 0.42% (0.25%–0.59%), respectively. A downward trend of the AAPC values of age-standardized YLD rate in men was shown in the vast majority of “B&R” countries, but for women, most countries had an upward trend. For adults aged 75 years or older, the age-standardized YLD rate showed an increasing trend in most of the “B&R” countries. Except for the DALY rate of lung cancer attributable to metabolic risks, a downward trend of the DALY rate attributable to all risk factors, behavioral risks, and environmental/occupational risks was shown in the vast majority of “B&R” countries.ConclusionThe burden of lung cancer in “B&R” countries varied significantly between regions, genders, and risk factors. Strengthening health cooperation among the “B&R” countries will help to jointly build a community with a shared future for mankind.

BackgroundA significant level of CD70 can be detected in various types of tumor tissues and CD27 is expressed on Treg cells, but CD70 expression is low in normal tissues. The interaction between CD70 and CD27 can stimulate the proliferation and survival of cancer cells and increase the level of soluble CD27, which is associated with poor prognosis in patients with lymphoma and certain solid tumors. Thus, it is a promising therapeutic target for the treatment of many major CD70+ cancer indications, including CD70+ lymphoma, RCC, NSCLC, HNSCC and OC.MethodsIMM40H was obtained through hybridoma screening and antibody humanization techniques. IMM40H was evaluated for its binding, blocking, Fc-dependent effector functions and antitumor activity characteristics in various in vitro and in vivo systems. The safety and tolerability profile of IMM40H were evaluated through single and repeated administration in cynomolgus monkeys.ResultsIn vitro cell-based assays demonstrated that IMM40H had considerably stronger CD70-binding affinity than competitor anti-CD70 antibodies, including cusatuzumab, which enabled it to block the interaction of between CD70 and CD27 more effectively. IMM40H also exhibited potent Fc-dependent effector functions (ADCC/CDC/ADCP), and could make a strong immune attack on tumor cells and enhance therapeutic efficacy. Preclinical findings showed that IMM40H had potent antitumor activity in multiple myeloma U266B1 xenograft model, and could eradicate subcutaneously established tumors at a low dose of 0.3 mg/kg. IMM40H (0.3 mg/kg) showed therapeutic effects faster than cusatuzumab (1 mg/kg). A strong synergistic effect between IMM01 (SIRPα-Fc fusion protein) and IMM40H was recorded in Burkitt’s lymphoma Raji and renal carcinoma cell A498 tumor models. In cynomolgus monkeys, the highest non-severely toxic dose (HNSTD) for repeat-dose toxicity was up to 30 mg/kg, while the maximum tolerated dose (MTD) for single-dose toxicity was up to 100 mg/kg, confirming that IMM40H had a good safety and tolerability profile.ConclusionIMM40H is a high-affinity humanized IgG1 specifically targeting the CD70 monoclonal antibody with enhanced Fc-dependent activities. IMM40H has a dual mechanism of action: inducing cytotoxicity against CD70+ tumor cells via various effector functions (ADCC, ADCP and CDC) and obstructs the proliferation and activation of Tregs by inhibiting CD70/CD27 signaling.

BackgroundEndoscopic submucosal dissection (ESD) for early gastric cancer (EGC) does not always lead to curative resection. Risk factors of lymph node metastasis (LNM)/local cancer residue after non-curative ESD for EGC have not been fully elucidated. We therefore aimed to clarify them and evaluate whether the “eCura system” is reliable for the risk stratification of LNM after non-curative ESD.MethodsWe conducted a multicenter retrospective study at seven institutions in Zhejiang, China, on 128 patients who underwent non-curative ESD for EGC. We divided the patients into two groups according to their therapeutic regimen after non-curative ESD. We analyzed the risk factors for LNM, local cancer residue, cancer recurrence, and cancer-specific mortality. Furthermore, we compared the outcomes in each risk category after applying the “eCura system”.ResultsAmong 68 patients undergoing additional surgery, LNM was found in three (4.41%) patients, while local cancer residue was found in eight (11.76%) patients. Multivariate analysis showed that upper third location and deep submucosal invasion were independent risk factors of LNM and local cancer residue. Among 60 patients who underwent simple follow-up, local cancer recurrence was found in four (6.67%) patients and cancer-specific mortality was found in one (1.67%) patient. There were no independent risk factors of cancer recurrence and cancer-specific mortality in our study. During the follow-up period, 5-year overall survival (OS) and disease-free survival (DFS) were 93.8% and 88.9%, respectively. Additionally, LNM and cancer recurrence were significantly associated with the eCura scoring system (p = 0.044 and p = 0.017, respectively), while local cancer residue and cancer-specific mortality were not (p = 0.478 and p = 0.131, respectively).ConclusionClinicians should be aware of the risk factors for the prognosis of patients with non-curative ESD to determine subsequent treatment. Through the application of the “eCura system”, additional surgery should be performed in patients with intermediate/high risk of LNM.

BackgroundAnlotinib showed encouraging anti-tumor activity in metastatic colorectal cancer (mCRC). This study was designed to assess the efficacy and safety of anlotinib plus XELOX as first-line therapy in mCRC patients.Materials and MethodsEligible patients aged ≥18 with mCRC were enrolled in this multicenter, single-arm, phase II, exploratory study. Patients received at least 6 cycles of anlotinib, oxaliplatin, and capecitabine as initial therapy. Subsequently, patients received anlotinib monotherapy as maintenance therapy until tumor progression or intolerable toxicity. The primary endpoint was progression-free survival (PFS).ResultsThirty-one patients were included between December 2019 and March 2022. The median follow-up was 17.5 (95% CI, 3.0-17.5) months. The median PFS was 8.3 (95% CI, 6.3-10.0) months, with 6- and 12-month PFS rates of 82.3% (95% CI, 59.2%-93.0%) and 18.9% (95% CI, 4.8%-40.1%), respectively. Fifteen (48.4%) achieved partial response for an ORR of 48.4% (95% CI, 30.2%-66.9%). The disease control rate was 71.0% (95% CI, 52.0%-85.8%) due to 7 (22.6%) stable diseases. The median duration of response was 6.0 (95% CI, 3.6-8.0) months and 1 patient had the longest ongoing response of 17.3 months. Of 24 patients with evaluable imaging, 23 (74.2%) obtained tumor shrinkage. The median PFS (11.0 vs. 6.9 months) and ORR (66.7% vs. 60.0%) for patients with RAS/BRAF wild-type were numerically better than those with mutation. Three patients are still ongoing treatment. The grade 3 or more treatment-emergent adverse events (TEAEs) were mainly hypertension (12.9%) and decreased neutrophil count (12.9%). Four (12.9%) had serious TEAEs, primarily including abdominal pain and incomplete intestinal obstruction.ConclusionAnlotinib plus XELOX as first-line therapy in patients with mCRC showed anti-tumor activity and safety profile, which is worth further investigation.Clinical Trial Registrationchictr.org.cn, identifier ChiCTR1900028417.

BackgroundThe overall survival of peripheral T-cell lymphoma (PTCL) is dismal. Histone deacetylase (HDAC) inhibitors have exhibited promising treatment outcomes for PTCL patients. Therefore, this work aims to systematically evaluate the treatment outcome and safety profile of HDAC inhibitor-based treatment for untreated and relapsed/refractory (R/R) PTCL patients.MethodsThe prospective clinical trials of HDAC inhibitors for the treatment of PTCL were searched on the Web of Science, PubMed, Embase, ClinicalTrials.gov, and Cochrane Library database. The pooled overall response rate, complete response (CR) rate, and partial response rate were measured. The risk of adverse events was evaluated. Moreover, the subgroup analysis was utilized to assess the efficacy among different HDAC inhibitors and efficacy in different PTCL subtypes.ResultsFor untreated PTCL, 502 patients in seven studies were involved, and the pooled CR rate was 44% (95% CI, 39-48%). For R/R PTCL patients, there were 16 studies included, and the CR rate was 14% (95% CI, 11-16%). The HDAC inhibitor-based combination therapy exhibited better efficacy when compared with HDAC inhibitor monotherapy for R/R PTCL patients (P = 0.02). In addition, the pooled CR rate was 17% (95% CI, 13-22%), 10% (95% CI, 5-15%), and 10% (95% CI, 5-15%) in the romidepsin, belinostat, and chidamide monotherapy subgroups, respectively. In the R/R angioimmunoblastic T-cell lymphoma subgroup, the pooled ORR was 44% (95% CI, 35-53%), higher than other subtypes. A total of 18 studies were involved in the safety assessment of treatment-related adverse events. Thrombocytopenia and nausea were the most common hematological and non-hematological adverse events, respectively.ConclusionThis meta-analysis demonstrated that HDAC inhibitors were effective treatment options for untreated and R/R PTCL patients. The combination of HDAC inhibitor and chemotherapy exhibited superior efficacy to HDAC inhibitor monotherapy in the R/R PTCL setting. Additionally, HDAC inhibitor-based therapy had higher efficacy in angioimmunoblastic T-cell lymphoma patients than that in other subtypes.

BackgroundSkin cutaneous melanoma (SKCM) is the deadliest type of cutaneous malignancy. Ubiquitination is a process of protein sorting and degradation that exhibits multiple functions in the progression of various tumors. This study aimed to characterize a set of genes for ubiquitination in SKCM.MethodsThe expression patterns of ubiquitin-associated genes (URGs) and the corresponding clinical information in SKCM tissues were comprehensively analyzed based on The Cancer Genome Atlas (TCGA) database. We performed univariate and multivariate Cox proportional regression models to characterize the risk scores and identify four critical genes related to prognostic ubiquitination (HCLS1, CORO1A, NCF1 and CCRL2), which were used to construct the prognostic signatures. We also studied the effects of HCLS1, CORO1A and CCRL2 on tumor metastasis-related indicators at the cellular level through in vitro experiments.ResultsSKCM patients in the low-risk group showing a longer survival than those in the high-risk group. Characteristic risk scores correlated with several clinicopathological variables and reflected the infiltration of multiple immune cells. In addition, the knockdown of CLS1, CORO1A and CCRL2 affected cellular malignant biological behavior through the EMT signaling pathway.ConclusionThis study provides a novel and prospective strategy to improve the clinical survival of SKCM patients.

BackgroundBabao Dan (BBD) is a traditional Chinese medicine that has been widely used as a complementary and alternative medicine to treat chronic liver diseases. In this study, we aimed to observe the effect of BBD on the incidence of diethylnitrosamine (DEN)-initiated hepatocellular carcinoma formation in rats and explored its possible mechanism.MethodsTo verify this hypothesis, BBD was administrated to rats at a dose of 0.5g/kg body weight per two days from the 9th to 12th week in HCC-induced by DEN. Liver injury biomarkers and hepatic inflammatory parameters were evaluated by histopathology as well as serum and hepatic content analysis. We applied immunohistochemical analysis to investigate the expression of CK-19 and SOX-9 in liver tissues. The expression of TLR4 was determined by immunohistochemical, RT-PCR, and western blot analysis. Furthermore, we also detected the efficacy of BBD against primary HPCs neoplastic transformation induced by LPS.ResultsWe observed that DEN could induce hepatocarcinogenesis, and BBD could obviously decrease the incidence. The biochemical and histopathological examination results confirmed that BBD could protect against liver injury and decrease inflammatory infiltration. Immunohistochemistry staining results showed that BBD could effectively inhibit the ductal reaction and the expression of TLR4. The results showed that BBD-serumcould obviously inhibit primary HPCs neoplastic transformation induced by regulating the TLR4/Ras/ERK signaling pathway.ConclusionIn summary, our results indicate that BBD has potential applications in the prevention and treatment of HCC, which may be related to its effect on hepatic progenitor cells malignant transformation via inhibiting the TLR4/Ras/ERK signaling pathway.

Purpose/backgroundMicrosatellite instability (MSI) status is a significant biomarker for the response to immune checkpoint inhibitors, response to 5-fluorouracil-based adjuvant chemotherapy, and prognosis in colorectal carcinoma (CRC). This study investigated the predictive value of intratumoral-metabolic heterogeneity (IMH) and conventional metabolic parameters derived from 18F-FDG PET/CT for MSI in patients with stage I–III CRC.MethodsThis study was a retrospective analysis of 152 CRC patients with pathologically proven MSI who underwent 18F-FDG PET/CT examination from January 2016 to May 2022. Intratumoral-metabolic heterogeneity (including heterogeneity index [HI] and heterogeneity factor [HF]) and conventional metabolic parameters (standardized uptake value [SUV], metabolic tumor volume [MTV], and total lesion glycolysis [TLG]) of the primary lesions were determined. MTV and SUVmean were calculated on the basis of the percentage threshold of SUVs at 30%–70%. TLG, HI, and HF were obtained on the basis of the above corresponding thresholds. MSI was determined by immunohistochemical evaluation. Differences in clinicopathologic and various metabolic parameters between MSI-High (MSI-H) and microsatellite stability (MSS) groups were assessed. Potential risk factors for MSI were assessed by logistic regression analyses and used for construction of the mathematical model. Area under the curve (AUC) were used to evaluate the predictive ability of factors for MSI.ResultsThis study included 88 patients with CRC in stages I–III, including 19 (21.6%) patients with MSI-H and 69 (78.4%) patients with MSS. Poor differentiation, mucinous component, and various metabolic parameters including MTV30%, MTV40%, MTV50%, and MTV60%, as well as HI50%, HI60%, HI70%, and HF in the MSI-H group were significantly higher than those in the MSS group (all P < 0.05). In multivariate logistic regression analyses, post-standardized HI60% by Z-score (P = 0.037, OR: 2.107) and mucinous component (P < 0.001, OR:11.394) were independently correlated with MSI. AUC of HI60% and our model of the HI60% + mucinous component was 0.685 and 0.850, respectively (P = 0.019), and the AUC of HI30% in predicting the mucinous component was 0.663.ConclusionsIntratumoral-metabolic heterogeneity derived from 18F-FDG PET/CT was higher in MSI-H CRC and predicted MSI in stage I–III CRC patients preoperatively. HI60% and mucinous component were independent risk factors for MSI. These findings provide new methods to predict the MSI and mucinous component for patients with CRC.

BackgroundLiver transplantation (LT) is one of the most effective treatment modalities for hepatocellular carcinoma (HCC), but patients with HCC recurrence after LT always have poor prognosis. This study aimed to evaluate the predictive value of the gamma-glutamyl transpeptidase-to-lymphocyte ratio (GLR) and systemic immune-inflammation index (SII) in terms of HCC recurrence after LT, based on which we developed a more effective predictive model.MethodsThe clinical data of 325 HCC patients who had undergone LT were collected and analyzed retrospectively. The patients were randomly divided into a development cohort (n = 215) and a validation cohort (n = 110). Cox regression analysis was used to screen the independent risk factors affecting postoperative recurrence in the development cohort, and a predictive model was established based on the results of the multivariate analysis. The predictive values of GLR, SII and the model were evaluated by receiver operating characteristic (ROC) curve analysis, which determined the cut-off value for indicating patients’ risk levels. The Kaplan-Meier survival analysis and the competing-risk regression analysis were used to evaluate the predictive performance of the model, and the effectiveness of the model was verified further in the validation cohort.ResultsThe recurrence-free survival of HCC patients after LT with high GLR and SII was significantly worse than that of patients with low GLR and SII (P

IntroductionCurrently, programmed cell death-1 (PD-1)-targeted treatment is ineffective for a sizable minority of patients, and drug resistance still cannot be overcome.MethodsTo explore the mechanisms of immunotherapy and identify new therapeutic opportunities in lung adenocarcinoma (LUAD), data from patients who did and did not respond to the anti-PD-1 treatment were evaluated using single-cell RNA sequencing, and bulk RNA sequencing were collected.ResultsWe investigated the gene expression that respond or not respond to immunotherapy in diverse cell types and revealed transcriptional characteristics at the single-cell level. To ultimately explore the molecular response or resistance to anti-PD-1 therapy, cell-cell interactions were carried out to identify the different LRIs (ligand-receptor interactions) between untreated patients vs. no-responders, untreated patients vs. responders, and responders vs. non-responders. Next, two molecular subgroups were proposed based on 73 LRI genes, and subtype 1 had a poor survival status and was likely to be the immunosuppressive tumor subtype. Furthermore, based on the LASSO Cox regression analysis results, we found that TNFSF13, AXL, KLRK1, FAS, PROS1, and CDH1 can be distinct prognostic biomarkers, immune infiltration levels, and responses to immunotherapy in LUAD.DiscussionAltogether, the effects of immunotherapy were connected to LRIs scores, indicating that potential medications targeting these LRIs could contribute to the clinical benefit of immunotherapy. Our integrative omics analysis revealed the mechanisms underlying the anti-PD-1 therapy response and offered abundant clues for potential strategies to improve precise diagnosis and immunotherapy.

As a recently named rare renal tumor of epithelial origin, papillary renal neoplasm with reverse polarity (PRNRP) has unique histomorphological features and immunophenotypes, often associated with KRAS mutations and showing indolent biological behavior. In this study, we report a case of PRNRP. In this report, nearly all tumor cells were positive for GATA-3, KRT7, EMA, E-Cadherin, Ksp-Cadherin, 34βE12, and AMACR in varying intensities, focally positive for CD10 and Vimentin, while negative for CD117, TFE3, RCC, and CAIX. KRAS mutations (exon 2) were detected by amplification refractory mutation system polymerase chain reaction (ARMS-PCR), while no NRAS (exon 2-4) and BRAF V600 mutations (exon 15) were detected. A transperitoneal Robot-Assisted Laparoscopic Partial Nephrectomy was performed on the reported patient. No recurrence or metastasis was found during the 18 months of follow-up.

IntroductionThe platelet-lymphocyte ratio (PLR), neutrophil-lymphocyte ratio (NLR), and systemic immune-inflammation index (SII) are markers for systemic inflammatory responses and have been shown by numerous studies to correlate with the prognosis of gastric cancer (GC). However, the diagnostic value of these three markers in GC is unclear, and no research has examined them in combination. In this study, we investigated the value of the PLR, NLR, and SII individually or in combination for GC diagnosis and elucidated the connection of these three markers with GC patients’ clinicopathological features.MethodsThis retrospective study was conducted on 125 patients diagnosed with GC and 125 healthy individuals, whose peripheral blood samples were obtained for analysis. The preoperative PLR, NLR, and SII values were subsequently calculated.ResultsThe results suggest that the PLR, NLR, and SII values of the GC group were considerably higher than those of the healthy group (all P ≤ 0.001); moreover, all three parameters were notably higher in early GC patients (stage I/II) than in the healthy population. The diagnostic value of each index for GC was analyzed using receiver operating characteristic (ROC) curve analysis and area under the curve (AUC) calculation. The diagnostic efficacy of the SII alone (AUC: 0.831; 95% confidence interval [CI], 0.777–0.885) was expressively better than those of the NLR (AUC: 0.821; 95% CI: 0.769–0.873, P = 0.017) and PLR (AUC: 0.783; 95% CI: 0.726–0.840; P = 0.020). The AUC value of the combination of the PLR, NLR, and SII (AUC: 0.843; 95% CI: 0.791–0.885) was significantly higher than that of the combination of the SII and NLR (0.837, 95% CI: 0.785–0.880, P≤0.05), PLR (P = 0.020), NLR (P = 0.017), or SII alone (P ≤ 0.001). The optimal cut-off values were determined for the PLR, NLR, and SII using ROC analysis (SII: 438.7; NLR: 2.1; PLR: 139.5). Additionally, the PLR, NLR, and SII values were all meaningfully connected with the tumor size, TNM stage, lymph node metastasis, and serosa invasion (all P ≤ 0.05). Elevated levels of the NLR and SII were linked to distant metastasis (all P ≤ 0.001).DiscussionThese data suggest that the preoperative PLR, NLR, and SII could thus be utilized as diagnostic markers for GC or even early GC. Among these three indicators, the SII had the best diagnostic efficacy for GC, and the combination of the three could further improve diagnostic efficiency.

Cholangiocarcinoma (CCA) is a highly malignant tumor of the hepatobiliary system that has failed to respond to many traditional therapies to a certain extent, including surgery, chemotherapy and radiotherapy. In recent years, the new therapeutic schemes based on immunology have fundamentally changed the systemic treatment of various malignant tumors to a certain extent. In view of the immunogenicity of CCA, during the occurrence and development of CCA, some immunosuppressive substances are released from cells and immunosuppressive microenvironment is formed to promote the escape immune response of its own cells, thus enhancing the malignancy of the tumor and reducing the sensitivity of the tumor to drugs. Some immunotherapy regimens for cholangiocarcinoma have produced good clinical effects. Immunotherapy has more precise characteristics and less adverse reactions compared with traditional treatment approaches. However, due to the unique immune characteristics of CCA, some patients with CCA may not benefit in the long term or not benefit at all after current immunotherapy. At present, the immunotherapy of CCA that have been clinically studied mainly include molecular therapy and cell therapy. In this article, we generalized and summarized the current status of immunotherapy strategies including molecular therapy and cell therapy in CCA in clinical studies, and we outlined our understanding of how to enhance the clinical application of these immunotherapy strategies.

BackgroundNon-muscle-invasive bladder cancer (NMIBC) is categorized into high and low grades with different clinical treatments and prognoses. Thus, accurate preoperative evaluation of the histologic NMIBC grade through imaging techniques is essential.ObjectivesTo develop and validate an MRI-based radiomics nomogram for individualized prediction of NMIBC grading.MethodsThe study included 169 consecutive patients with NMIBC (training cohort: n = 118, validation cohort: n = 51). A total of 3148 radiomic features were extracted, and one-way analysis of variance and least absolute shrinkage and selection operator were used to select features for building the radiomics score(Rad-score). Three models to predict NMIBC grading were developed using logistic regression analysis: a clinical model, a radiomics model and a radiomics–clinical combined nomogram model. The discrimination and calibration power and clinical applicability of the models were evaluated. The diagnostic performance of each model was compared by determining the area under the curve (AUC) in receiver operating characteristic (ROC) curve analysis.ResultsA total of 24 features were used to build the Rad-score. A clinical model, a radiomics model, and a radiomics–clinical nomogram model that incorporated the Rad-score, age, and number of tumors were constructed. The radiomics model and nomogram showed AUCs of 0.910 and 0.931 in the validation set, which outperformed the clinical model (0.745). The decision curve analysis also showed that the radiomics model and combined nomogram model yielded higher net benefits than the clinical model.ConclusionA radiomics–clinical combined nomogram model has the potential to be used as a non-invasive tool for the differentiating low-from high-grade NMIBCs.

BackgroundCarbon nanoparticles (CNs) have been widely used in the protection of the parathyroid gland and act as a tracer agent in central lymph node dissection. However, the right time for CN injection has not been well illustrated in the transoral endoscopic thyroidectomy vestibular approach (TOETVA). The purpose of this study was to evaluate the safety and feasibility of the preoperative injection of CNs in TOETVA for papillary thyroid cancer.MethodsFrom October 2021 to October 2022, a total of 53 consecutive patients with PTC were retrospectively analyzed. All patients underwent unilateral thyroidectomy via the TOETVA. The patients were divided into the preoperative group (n = 28) and the intraoperative group (n = 25) according to CN injection time. In the preoperative group, 0.2 ml of CNs were injected into the thyroid lobules with malignant nodules 1 h before surgery. The numbers of total central lymph node (CLN) and metastatic central lymph node (CLNM), parathyroid autotransplantation, accidental removal of the parathyroid, and the parathyroid hormone level were recorded and analyzed.ResultsThe leakage of CNs happened more frequently in the intraoperative group than in the preoperative group (P = 0.002). The mean number of retrieved CLN and CLNM was similar in the preoperative group and the intraoperative group. In parathyroid protection, more parathyroid was discovered in the preoperative group than in the intraoperative group (1.57 ± 0.54 vs. 1.47 ± 0.50, P = 0.002), but less parathyroid autotransplantation (P = 0.004) and accidental removal of the parathyroid (P = 0.036) were discovered in the preoperative group. However, the PTH level between the two groups was similar after the first day and the first month.ConclusionThe preoperative injection of CNs is a safe and effective method to protect the parathyroid glands (PGs) in patients with PTC undergoing TOETVA. However, the value of preoperative injection of CNs in TOETVA for central lymph node dissection needs to be further studied.

IntroductionHydrometra is a common gynecological disease, especially in postmenopausal women. However, its epidemiology, harmfulness, and value in predicting gynecological tumors have not been clearly elucidated.MethodsIn this study, the prevalence rate of and risk factors for hydrometra were investigated in 3,903 women who underwent screening for gynecological diseases at Zhoupu Hospital in Shanghai from 1 January to 31 December 2021. In addition, pathological distribution of hydrometra and its predictive value in gynecological tumors were studied in another 186 patients in whom hydrometra was diagnosed sonographically at Zhoupu Hospital, from 1 January 2020 to 31 December 2021, and who underwent hysteroscopy and postoperative pathological examination.ResultsThe observed prevalence rate of hydrometra was 10.86%, which was higher than the prevalence of other gynecological diseases. Univariate and multivariate analysis indicated that advanced age (OR 1.11) and vaginitis (OR 3.18) were independent risk factors for hydrometra. Among 186 patients with a sonographic diagnosis of uterine fluid, simple hydrometra accounted for 34.41% of cases, inflammation accounted for 16.23%, and hematometra accounted for 2.15%, while gynecological tumors accounted for 5.91%. Moreover, univariate and multivariate analysis indicated that a higher body mass index (>23.92 kg/m2), greater hydrometra volume (i.e., distance between the two layers of endometrium>4.75 mm), and abnormal vaginal bleeding were high-risk predictive factors for gynecological tumors.DiscussionIn conclusion, hydrometra is a common disease, and is a risk factor for endometrial cancer and cervical cancer, especially in patients with higher hydrometra volume, higher BMI, and abnormal vaginal bleeding. It is necessary to pay more attention to hydrometra.

Cancer immunotherapy shows durable treatment responses and therapeutic benefits compared to other cancer treatment modalities, but many cancer patients display primary and acquired resistance to immunotherapeutics. Immunosuppressive tumor microenvironment (TME) is a major barrier to cancer immunotherapy. Notably, cancer cells depend on high mitochondrial bioenergetics accompanied with the supply of heme for their growth, proliferation, progression, and metastasis. This excessive mitochondrial respiration increases tumor cells oxygen consumption, which triggers hypoxia and irregular blood vessels formation in various regions of TME, resulting in an immunosuppressive TME, evasion of anti-tumor immunity, and resistance to immunotherapeutic agents. In this review, we discuss the role of heme, heme catabolism, and mitochondrial respiration on mediating immunosuppressive TME by promoting hypoxia, angiogenesis, and leaky tumor vasculature. Moreover, we discuss the therapeutic prospects of targeting heme and mitochondrial respiration in alleviating tumor hypoxia, normalizing tumor vasculature, and TME to restore anti-tumor immunity and resensitize cancer cells to immunotherapy.

IntroductionTo explore the prognostic value of CT-based delta radiomics in predicting the prognosis of patients with stage IV gastric cancer treated with immune checkpoint inhibitors (ICI).Materials and methodsForty-two patients with stage IV gastric cancer, who had received ICI monotherapy, were enrolled in this retrospective study. Baseline and first follow-up CT scans were analyzed. Intratumoral and peritumoral regions of interest (ROI) were contoured, enabling the extraction of 192 features from each ROI. The intraclass correlation coefficients were used to select features with high stability. The least absolute shrinkage and selection operator was used to select features with high weights for predicting patient prognosis. Kaplan–Meier analysis and log-rank test were performed to explore the association between features and progression free survival (PFS). Cox regression analyses were used to identify predictors for PFS. The C-index was used to assess the prediction performance of features.ResultsTwo radiomics features of ΔVintra_ZV and postVperi_Sphericity were identified from intratumoral and peritumoral regions, respectively. The Kaplan–Meier analysis revealed significant differences in PFS between patients with low and high feature value (ΔVintra_ZV: P=0.000; postVperi_Sphericity: P=0.012), and the multivariable cox analysis demonstrated that ΔVintra_ZV was independent predictor for PFS (HR, 1.911; 95% CI: 1.163–3.142; P=0.011), with C-index of 0.705.ConclusionsBased on CT scans at baseline and first follow-up, the delta radiomics features could efficiently predict the PFS of gastric cancer patients treated with ICI therapy.

BackgroundHepatocellular carcinoma (HCC) is a well-described complication of Budd-Chiari syndrome (BCS). However, the risk factors of BCS in developing HCC and clinical characteristics and imaging features of BCS-associated HCC is still to be determined.MethodsData from 113 consecutive patients with primary BCS in Qilu hospital were retrospectively studied. The clinical features of 12 HCC patients associated with BCS were also analyzed. Chi-square analysis was performed to analyze the differences in clinical characteristics. The treatment regime and CT imaging features of BCS-associated HCC were also illustrated.Results113 consecutive patients admitted to our hospital between January 2009 and June 2016 with a primary diagnosis of BCS were enrolled. 10.6% (12/113) was diagnosed with HCC. The BCS patients were mainly male gender with an average age of 49.2 years. Symptom duration longer than one year exhibited decreased serum ALT and AST and increased ascites ratio. BCS-associated HCC patients were presented with IVC block and stricture of the hepatic venous outflow tract. Patients with HCC were older and showed elevated serum AST and total bilirubin. Most nodules of HCC located in the right posterior lobe with heterogeneous enhancement during the arterial phase and washout during the delayed phase.ConclusionsThe results indicate that BCS patients with IVC block and stricture of hepatic venous outflow tract seem to be associated with HCC. BCS associated HCC nodules exhibited irregular and heterogeneous enhancement in the arterial phase and washout on the delayed phase.

ObjectivesTo investigate the short-term efficacy and radiotoxicity 3.543of chronoradiotherapy in patients with cervical cancer. We also examined the overall symptom score and quality of life (QOL) of patients who underwent morning radiotherapy and evening radiotherapy.MethodsWe conducted a multicenter randomized controlled trial to compare the effects of morning radiotherapy (9:00–11:00 AM) with evening radiotherapy (7:00–9:00 PM) in cervical cancer patients receiving radiotherapy. From November 2021 to June 2022, 114 cervical cancer patients admitted to eight cancer center hospitals in Tianjin, Chongqing, Hubei, Shanxi, Shandong, Shaanxi, Hebei, and Cangzhou were randomly divided into the morning radiotherapy group (MG; N = 61) and the evening radiotherapy group (EG; N = 53). The short-term efficacy of radiotherapy on cervical cancer patients at different time points and the occurrence of radiotoxicity were explored after patients had undergone radiotherapy.ResultsThe total effective response (partial remission [PR] + complete remission [CR]) rate was similar across the two groups (93.5% vs. 96.3%, p > 0.05). However, the incidence of bone marrow suppression and intestinal reaction in the two groups were significantly different (p < 0.05). The patients in the MG had significantly higher Anderson symptom scores than patients in the EG (21.64 ± 7.916 vs. 18.53 ± 4.098, p < 0.05). In terms of physical activity, functional status, and overall QOL, the MG had significantly lower scores than the EG (p < 0.05). No other measures showed a significant difference between the groups.ConclusionThe radiotherapy effect of the MG was consistent with that of the EG. The incidence of radiation enteritis and radiation diarrhea in the MG was significantly higher than that in the EG; however, bone marrow suppression and blood toxicity in the EG were more serious than in the MG. Because of the small sample size of the study, we only examined the short-term efficacy of radiotherapy. Therefore, further clinical trials are needed to verify the efficacy and side effects of chronoradiotherapy.Clinical Trial Registrationhttp://www.chictr.org.cn/searchproj.aspx, Registration Number: ChiCTR2100047140.

In recent years, many clinical trials have shown the safety and efficacy of Gemogenovatucel-T (Vigil) in the treatment of advanced OC patients. The purpose of this study was to explore the safety and efficacy of Gemogenovatucel-T (Vigil) in the first-line maintenance of advanced ovarian carcinoma based on the randomized controlled trials (RCTs). Randomized controlled trials (RCTs) on Gemogenovatucel-T (Vigil) immunotherapy for advanced ovarian carcinoma were searched in PubMed, Embase, Cochrane Library and Web of Science up to December 31, 2021. The following study characteristics were investigated: baseline study characteristics, overall survival, recurrence free survival, recurrence free survival median time, and complication. A total of 36 articles were obtained, and seven suitable RCTs with a total sample size of 322 patients were eventually included in this meta-analysis. Overall survival (OS): from time of randomization: HR=0.48 (95% CI: 0.32 to 0.72), Z=3.55, P

It has been established that long-chain coding RNA (lncRNA) SLC25A25-AS1 is associated with cancer progression. However, the roles and mechanisms of SLC25A25-AS1 in prostate cancer (PC) have not been reported in the literature. The present study explored the relationship between SLC25A25-AS1 expression and PC progression via comprehensive analysis. The pan-cancer expression of SLC25A25-AS1 was identified using data from The Cancer Genome Atlas (TCGA) database and tissue specimens from our hospital. The expression levels of SLC25A25-AS1 in various subgroups based on the clinical features were identified. The prognostic value of SLC25A25-AS1 and SLC25A25-AS1 co-expressed lncRNAs in PC patients was assessed by survival analysis and ROC analysis, and prognosis-related risk models of SLC25A25-AS1 were constructed. The relationship between SLC25A25-AS1 and the PC immune microenvironment was investigated using correlation analysis. SLC25A25-AS1 expression in PC was significantly increased and correlated with the T stage, clinical stage, Gleason score (GS), and dismal prognosis. SLC25A25-AS1 overexpression exhibited good performance in evaluating the prognosis of PC patients. The area under the curves (AUCs) of the 1-, 3-, and 5-year overall survival (OS) for SLC25A25-AS1 was 1, 0.876, and 0.749. Moreover, the AUCs for the 1-, 3-, and 5-year progress free interval (PFI) for SLC25A25-AS1 were 0.731, 0.701, and 0.718. SLC25A25-AS1 overexpression correlated with the infiltration of CD8 T cells, interstitial dendritic cells (IDC), macrophages and other cells. AC020558.2, ZNF32-AS2, AP4B1-AS1, AL355488.1, AC109460.3, SNHG1, C3orf35, LMNTD2-AS1, and AL365330.1 were significantly associated with SLC25A25-AS1 expression, and short OS and PFI in PC patients. The risk models of the SLC25A25-AS1-related lncRNAs were associated with a dismal prognosis in PC. Overall, SLC25A25-AS1 expression was increased in PC and related to the prognosis and PC immune microenvironment. The risk model of SLC25A25-AS1 have huge prospect for application as prognostic tools in PC.

BackgroundCervical cancer, as a common gynecological disease, endangers female health. Give the lack of effective biomarkers for the diagnosis and treatment of cervical cancer, this paper aims to analyze the Gene Expression Omnibus (GEO) data sets using comprehensive bioinformatics tools, and to identify biomarkers associated with the cancer in patient samples.MethodsThe bioinformatics methods were used to extract genes related to cervical cancer from GSE39001, while the GEO2R online tool to elaborate on differentially expressed genes (DEGs) in normal and cancer samples, and to clarify related genes and functions. The results were verified by IHC, WB, CCK-8, clone formation and flow cytometry experiments.ResultsA total of 2,859 DEGs were identified in the GEO microarray dataset. We extracted genes associated with both ubiquitination and autophagy from the key modules of weighted gene co-expression network analysis (WGCNA), and the analysis showed that TRIM8 was of great significance for the diagnosis and prognosis of cervical cancer. Besides, experimental validation showed the high TRIM8 expression in cervical cancer, as well as its involvement in the proliferation of cervical cancer cells.ConclusionWe identified a biomarker (TRIM8) that may be related to cervical cancer through a series of analyses on the GEO dataset. Experimental verification confirmed the inhibition of cervical cancer cells proliferation by lowering TRIM8 expression. Therefore, TRIM8 can be adopted as a new biomarker of cervical cancer to develop new therapeutic targets.

Non-Down’s syndrome acute megakaryocytic leukemia (non-DS-AMKL) is a subtype of childhood acute myeloid leukemia (AML), whose prognosis, prognostic factors and treatment recommendations have not yet to be defined in children. We conducted a retrospective study with 65 newly diagnosed non-DS-AMKL children from August 2003 to June 2020 to investigate the clinical impact of factors and clinical outcome. Among all 65 patients, 47 of them were treated at our center who received three different regimens due to time point of admission (CAMS-another, CAMS-2009 and CAMS-2016 protocol), and the efficacy were compared. Patients with newly diagnosed non-DS-AMKL accounted for 7.4% of pediatric AML cases. The median age of the patients was 18 months at diagnosis, and over 90% of them were under three-years-old. The overall survival (OS) rates were 33.3% ± 1.7%, 66.7% ± 24.4% and 74.2% ± 4.0% for three groups (CAMS-another, CAMS-2009 and CAMS-2016 regimen), respectively. In CAMS-2016 group, the complete remission (CR) rate after induction was 67.7% (21/31), while the total CR rate after all phases of chemotherapy was 80.6% (25/31). The 2-year survival probability did not significantly improve in patients underwent HSCT when compared with non-HSCT group (75.0% ± 4.7% vs. 73.9% ± 4.6%, p=0.680). Those who had a “dry tap” during BM aspiration at admission had significantly worse OS than those without “dry tap” (33.3% ± 8.6% vs. 84.0% ± 3.6%, p=0.006). Moreover, the results also revealed that patients with CD34+ had significantly lower OS (50.0% ± 6.7% vs. 89.5% ± 3.5%, p=0.021), whereas patients with CD36+ had significantly higher OS than those who were negative (85.0% ± 4.0% vs. 54.5% ± 6.6%, p=0.048). In conclusion, intensive chemotherapy resulted in improved prognosis of non-DS-AMKL children and subclassification may base on “dry tap” and immunophenotypic. Although some progress has been made, outcomes of non-DS-AMKL children remain unsatisfactory, especially in HSCT group, when compared with other AML types.

Liver cancer is one of the most common cancers in the world, and the rate of liver cancer is high due to the of its illness. The main risk factor for liver cancer is infection with the hepatitis B virus (HBV), but a considerable number of genetic and epigenetic factors are also directly or indirectly involved in the underlying pathogenesis of liver cancer. In particular, the apolipoprotein B mRNA editing enzyme, catalytic peptide-like protein (APOBEC) family (DNA or mRNA editor family), which has been the focus of virology research for more than a decade, has been found to play a significant role in the occurrence and development of various cancers, providing a new direction for the research of liver cancer. APOBEC3B is a cytosine deaminase that controls a variety of biological processes, such as protein expression, innate immunity, and embryonic development, by participating in the process of cytidine deamination to uridine in DNA and RNA. In humans, APOBEC3B has long been known as a DNA editor for limiting viral replication and transcription. APOBEC3B is widely expressed at low levels in a variety of normal tissues and organs, but it is significantly upregulated in different types of tumor tissues and tumor lines. Thus, APOBEC3B has received increasing attention in various cancers, but the role of APOBEC3B in the occurrence and development of liver cancer due to infection with HBV remains unclear. This review provides a brief introduction to the pathogenesis of hepatocellular carcinoma induced by HBV, and it further explores the latest results of APOBEC3B research in the development of HBV and liver cancer, thereby providing new directions and strategies for the treatment and prevention of liver cancer.

Transcriptome profiling of hepatocellular carcinoma (HCC) by next-generation sequencing (NGS) technology has been broadly performed by previous studies, which facilitate our understanding of the molecular mechanisms of HCC formation, progression, and metastasis. However, few studies jointly analyze multiple types of noncoding RNAs (ncRNAs), including long noncoding RNAs (lncRNAs), circular RNAs (circRNAs), and micro-RNAs (miRNAs), and further uncover their implications in HCC. In this study, we observed that the circRNA cZRANB1 and lncRNA DUXAP10 were not only significantly upregulated in tumor tissues, but also higher expressed in blood exosomes of HCC as compared with healthy donors. From the analysis of subclass-associated dysregulated ncRNAs, we observed that DLX6-AS1, an antisense RNA of DLX6, and the sense gene DLX6 were highly expressed in S1, a subclass with a more invasive/disseminative phenotype. High correlation between DLX6-AS1 and DLX6 suggested that DLX6-AS1 may function via promoting the transcription of DLX6. Integrative analysis uncovers circRNA–miRNA, lncRNA–miRNA, and competing endogenous RNA networks (ceRNAs). Specifically, cZRANB1, LINC00501, CTD-2008L17.2, and SLC7A11-AS1 may function as ceRNAs that regulate mRNAs by competing the shared miRNAs. Further prognostic analysis demonstrated that the dysregulated ncRNAs had the potential to predict HCC patients’ overall survival. In summary, we identified some novel circRNAs and miRNAs, and dysregulated ncRNAs that could participate in HCC tumorigenesis and progression by inducing transcription of their neighboring genes, increasing their derived miRNAs, or acting as miRNA sponges. Moreover, our systematic analysis provides not only rich data resources for related researchers, but also new insights into the molecular basis of how different ncRNAs coordinately or antagonistically participate in the pathogenesis process of diseases.

Primary vitreoretinal lymphoma (PVRL) is a rare variant of primary central nervous system lymphoma (PCNSL) that presents diagnostic challenges. Here, we focused on circulating cell-free DNA (cfDNA) and interleukin-10 (IL-10) isolated from cerebrospinal fluid. Twenty-three VRL patients (17 PVRL, 2 PCNSL/O, and 4 relapsed VRL, from 10/2018 to 12/2021) and 8 uveitis patients were included in this study. CSF samples from 19 vitreoretinal lymphoma patients had sufficient cfDNA for next-generation sequencing. Of these patients, 73.7% (14/19) had at least one meaningful non-Hodgkin lymphoma-related mutation. The characteristic MYD88L265P mutation was detected in the CSF of 12 VRL patients, with a sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of 63.2%, 100%, 100%, and 46.2%, respectively. No meaningful lymphoma related mutations were found in CSF samples from uveitis controls with typical intraocular lesions. Meanwhile, CSF IL-10 levels were elevated in 95.7% of the VRL patients, with a sensitivity, specificity, PPV, and NPV of 95.7%, 100%, 100% and 88.9%, respectively. Key somatic mutations like MYD88L265P and CD79B detected from CSF cfDNA and elevated CSF IL-10 levels can be promising adjuncts for primary vitreoretinal lymphoma diagnosis.

Antibodies targeting the programmed cell death protein-1 (PD-1) molecule have been reported to hold promising antitumor activities in patients with nasopharyngeal carcinoma (NPC). However, only a small subset of NPC patients benefits from the anti-PD-1 monotherapy and factors that affect the treatment response need further investigation. This study aimed to examine the impact of multiple genetic and environmental factors on outcome of anti-PD-1 immunotherapy by identifying tumor size, tumor mutation burden (TMB) based on whole exon sequencing, human leukocyte antigen class I (HLA-I) homo-/heterozygosity and supertypes, blood Epstein-Barr virus (EBV) DNA load, T cell proportions, and interferon-γ(IFN-γ) levels in a cohort of 57 NPC patients that received Nivolumab or Camrelizumab treatment. Moreover, we profiled the longitudinal changes in gut microbiota composition using shotgun metagenomics sequencing. We observed that high TMB combined with HLA-I heterozygosity was associated with improved clinical outcomes. In agreement with previous studies, we found that patients with higher plasma EBV DNA load showed worse progression-free survival. We found no evidence for an effect of gut bacterial diversity on the treatment response, but identified a higher abundance of seven specific gut bacteria at baseline of non-responders, including Blautia wexlera and Blautia obeum, as well as four other bacteria belonging to the Clostridiales order, and one Erysipelatoclostridium. Combined, this study provides insight into the influence of several genetic and environmental factors on anti-PD-1 immunotherapy responses in NPC patients.

BackgroundTreatments for patients with early‐stage hepatocellular carcinoma (HCC) include liver transplantation (LT), liver resection (LR), radiofrequency ablation (RFA), and microwave ablation (MWA), are critical for their long-term survival. However, a computational model predicting treatment-independent prognosis of patients with HCC, such as overall survival (OS) and recurrence-free survival (RFS), is yet to be developed, to our best knowledge. The goal of this study is to identify prognostic factors associated with OS and RFS in patients with HCC and develop nomograms to predict them, respectively.MethodsWe retrospectively retrieved 730 patients with HCC from three hospitals in China and followed them up for 3 and 5 years after invasive treatment. All enrolled patients were randomly divided into the training cohort and the validation cohort with a 7:3 ratio, respectively. Independent prognostic factors associated with OS and RFS were determined by the multivariate Cox regression analysis. Two nomogram prognostic models were built and evaluated by concordance index (C-index), calibration curves, area under the receiver operating characteristics (ROC) curve, time-dependent area under the ROC curve (AUC), the Kaplan–Meier survival curve, and decision curve analyses (DCAs), respectively.ResultsPrognostic factors for OS and RFS were identified, and nomograms were successfully built. Calibration discrimination was good for both the OS and RFS nomogram prediction models (C-index: 0.750 and 0.746, respectively). For both nomograms, the AUC demonstrated outstanding predictive performance; the DCA shows that the model has good decision ability; and the calibration curve demonstrated strong predictive power. The nomograms successfully discriminated high-risk and low-risk patients with HCC associated with OS and RFS.ConclusionsWe developed nomogram survival prediction models to predict the prognosis of HCC after invasive treatment with acceptable accuracies in both training and independent testing cohorts. The models may have clinical values in guiding the selection of clinical treatment strategies.

BackgroundEstablishing risk-based follow-up management strategies is crucial to the surveillance of subsolid pulmonary nodules (SSNs). However, the risk factors for SSN growth are not currently clear. This study aimed to perform a systematic review and meta-analysis to identify clinical and CT features correlated with SSN growth.MethodsRelevant studies were retrieved from Web of Science, PubMed, Cochrane Library, and EMBASE. The correlations of clinical and CT features with SSN growth were pooled using a random-effects model or fixed-effects model depending on heterogeneity, which was examined by the Q test and I2 test. Pooled odds ratio (OR) or pooled standardized mean differences (SMD) based on univariate analyses were calculated to assess the correlation of clinical and CT features with SSN growth. Pooled ORs based on multivariate analyses were calculated to find out independent risk factors to SSN growth. Subgroup meta-analysis was performed based on nodule consistency (pure ground-glass nodule (pGGN) and part-solid nodule (PSN). Publication bias was examined using funnel plots.ResultsNineteen original studies were included, consisting of 2444 patients and 3012 SSNs. The median/mean follow-up duration of these studies ranged from 24.2 months to 112 months. Significant correlations were observed between SSN growth and eighteen features. Male sex, history of lung cancer, nodule size > 10 mm, nodule consistency, and age > 65 years were identified as independent risk factors for SSN growth based on multivariate analyses results. Eight features, including male sex, smoking history, nodule size > 10 mm, larger nodule size, air bronchogram, higher mean CT attenuation, well-defined border, and lobulated margin were detected to be significantly correlated with pGGNs growth. Smoking history showed no significant correlation with pGGN growth based on the multivariate analysis results.ConclusionsEighteen clinical and CT features were identified to be correlated with SSN growth, among which male sex, history of lung cancer, nodule size > 10 mm, nodule consistency and age > 65 years were independent risk factors while history of lung cancer was not correlated with pGGN growth. These factors should be considered when making risk-based follow-up plans for SSN patients.

ObjectiveThe mortality rate of ovarian cancer (OC) is the highest among all gynecologic cancers. To predict the prognosis and the efficacy of immunotherapy, we identified new biomarkers.MethodsThe Cancer Genome Atlas (TCGA) and the Genotype-Tissue Expression Project (GTEx) databases were used to extract ovarian cancer transcriptomes. By performing the co-expression analysis, we identified necroptosis-associated long noncoding RNAs (lncRNAs). We used the least absolute shrinkage and selection operator (LASSO) to build the risk model. The qRT-PCR assay was conducted to confirm the differential expression of lncRNAs in the ovarian cancer cell line SK-OV-3. Gene Set Enrichment Analysis, Kaplan-Meier analysis, and the nomogram were used to determine the lncRNAs model. Additionally, the risk model was estimated to evaluate the efficacy of immunotherapy and chemotherapy. We classified necroptosis-associated IncRNAs into two clusters to distinguish between cold and hot tumors.ResultsThe model was constructed using six necroptosis-associated lncRNAs. The calibration plots from the model showed good consistency with the prognostic predictions. The overall survival of one, three, and five-year areas under the ROC curve (AUC) was 0.691, 0.678, and 0.691, respectively. There were significant differences in the IC50 between the risk groups, which could serve as a guide to systemic treatment. The results of the qRT-PCR assay showed that AL928654.1, AL133371.2, AC007991.4, and LINC00996 were significantly higher in the SK-OV-3 cell line than in the Iose-80 cell line (P < 0.05). The clusters could be applied to differentiate between cold and hot tumors more accurately and assist in accurate mediation. Cluster 2 was more vulnerable to immunotherapies and was identified as the hot tumor.ConclusionNecroptosis-associated lncRNAs are reliable predictors of prognosis and can provide a treatment strategy by screening for hot tumors.

BackgroundOrthotopic liver transplantation (OLT) is a life-saving option for patients with hepatocellular carcinoma (HCC), but the expanded OLT criteria remain controversial.ObjectiveThe study aimed to explore whether expanded OLT criteria can be applied to Chinese cirrhotic patients with HCC.MethodsThis retrospective study analyzed risk factors for HCC recurrence and death and compared patients’ tumor characteristics and outcomes in groups of Milan, “Up-to-seven,” and Hangzhou criteria, and groups between met and unmet the combinative criteria of “Up-to-seven” and AFP of < 1000 ng/mL.ResultsAmong 153 patients who underwent OLT for HCC from January 2015 to February 2019 in 4 years of follow-up, 20 (13.1%) patients had HCC recurrence, and 11 (7.2%) had HCC-related death. Multivariate Cox regression analysis showed that preoperative alpha-fetoprotein (AFP) of > 1000 ng/mL (hazard ratio [HR]: 10.05, 95% confidence interval [CI]: 2.45–41.13, P = 0.001) was an independent risk factor for HCC recurrence and HCC-related death (HR: 6.63, 95%CI: 1.31–33.52, P = 0.022). Patients who did not meet Milan criteria but satisfied the “Up-to-seven” criteria had no differences in overall survival (OS) (P = 0.69) and disease-free survival (DFS) (P = 0.35) than patients who met the Milan criteria. The combination of “Up-to-seven” criteria and AFP of < 1000 ng/mL differed significantly (HR: 18.9; 95% CI: 4.0–89.2; P < 0.001). Patients with HCC who met the “Up-to-seven” criteria and AFP of < 1000 ng/mL (n = 121) had excellent survival with 4-year OS of 91.6% (P < 0.001) and DFS of 90.8% (P < 0.001), which is significantly better compared to the other group (n = 32) (OS of 67.5% and DFS of 46.5%) and patients who met the Milan criteria (n = 108, OS of 89.8%, DFS of 89.6%), allowing 28.9% (13/45) of patients who did not meet the Milan criteria to benefit from OLT.ConclusionChinese cirrhotic patients with HCC who met the combinative criteria of “Up-to-seven” and AFP of < 1000 ng/mL had better survival than those who met the Milan criteria, and these combinative criteria benefited more patients and may become a better option for OLT.

Sintilimab combined with pemetrexed and platinum met the primary endpoint of improving progression-free survival (PFS) as a first-line therapy for nonsquamous non-small cell lung cancer (NSCLC) in the phase 3 trial ORIENT-11 (NCT03607539). As seen in similar trials, the addition of sintilimab, a PD-1 inhibitor, to chemotherapy improved the PFS without significantly worsening the toxicity, with improvements in response rate and duration of response. In contrast to previous trials, the ORIENT-11 trial was conducted completely in China. Both intrinsic and extrinsic factors are important to consider when reviewing foreign clinical trial data, as they may influence the efficacy and the safety outcomes. Here we discuss the applicability of ORIENT-11 clinical results to a Western population.

Background and AimsAptamers are artificial ligands that bind to biological targets with high specificity and affinity. We previously selected a group of aptamers against the serum of primary hepatic carcinoma (PHC) via systematic evolution of ligands by exponential and enrichment (SELEX) method, and some of the aptamers were valuable for PHC diagnosis in polyacrylamide gel electrophoresis (PAGE) analysis. Here, we used aptamers to develop a novel method suitable for the clinical diagnosis of PHC.MethodsThe intensities of serum autofluorescence, cell-free DNA (cfDNA)-related fluorescence and aptamer-related fluorescence, named the aptamer-based triple serum fluorescence intensity (ATSFI), were sequentially measured at 8 °C and 37 °C in one tube by using a real-time polymerase chain reaction (PCR) system as a fluorimeter in patients with PHC (n=346) or liver cirrhosis (n=321). The diagnostic performances of ATSFI indicators alone and in combination were evaluated by area under the receiver operator characteristic curve (AUROC), and the underlying clinical mechanisms were analyzed by bivariate correlation.ResultsThe measurement of ATSFI was high throughput, rapid, convenient, and low cost. The aptamer-related fluorescence indicator SEA-SE37 was the most valuable for PHC diagnosis among all fluorescence indicators and superior to alpha-fetoprotein (AFP) (AUROC 0.879 vs. 0.836). The logistic model of ATSFI indicators exhibited excellent diagnostic performance for PHC, including AFP-negative, early and small PHCs, with AUROCs of 0.935-0.950 and accuracies of 86.8-88.3%. The diagnostic performance was further improved when ATSFI indicators were combined with AFP, with AUROCs of approximately 0.95 and accuracies of approximately 90%, suggesting ATSFI was independent of but complementary to AFP in PHC diagnosis. ATSFI models were highly valuable in clinical decision-making. The aptamer-related fluorescence intensity was generally independent of the clinicopathological characteristics of PHC but correlated with laboratory characteristics of PHC serum.ConclusionsThe ATSFI assay is a novel, robust and feasible method for the clinical diagnosis of PHC.

Estrogen receptor (ER)-positive breast cancer is the main subtype of breast cancer (BRCA) with high incidence and mortality. Andrographolide (AD), a major active component derived from the traditional Chinese medicine Andrographis paniculate, has substantial anti-cancer effect in various tumors. However, the antitumor efficacy and the underlying molecular mechanisms of AD on ER-positive breast cancer are poorly understood. In the present study, we demonstrated that andrographolide (AD) significantly inhibited the growth of ER-positive breast cancer cells. Mechanistically, AD suppressed estrogen receptor 1 (ESR1, encodes ER-α) transcription to inhibit tumor growth. Further studies revealed that AD induced ROS production to down-regulate FOXM1-ER-α axis. Conversely, inhibiting ROS production with N-acetylcysteine (NAC) elevated AD-decreased ER-α expression, which could be alleviated by FOXM1 knockdown. In addition, AD in combination with fulvestrant (FUL) synergistically down-regulated ER-α expression to inhibit ER-positive breast cancer both in vitro and in vivo. These findings collectively indicate that AD suppresses ESR1 transcription through ROS-FOXM1 axis to inhibit ER-positive breast cancer growth and suggest that AD might be a potential therapeutic agent and fulvestrant sensitizer for ER-positive breast cancer treatment.

BackgroundHepatocellular carcinoma (HCC) is inflammation-related cancer. Persistent inflammatory injury of the liver is an important factor mediating the occurrence and development of liver cancer. Hepatic macrophages play an important role in the inflammatory microenvironment, which mediates tumor immune escape, tumor growth, and metastasis. Previous studies have suggested that L-3,5,3-triiodothyronine (T3) can regulate inflammation; however, its use is associated with serious cardiac side effects, and its role in hepatocarcinogenesis remains unclear. In this study, we aimed to develop an effective T3 delivery system with reduced cardiac toxicity and to explore its effects on HCC occurrence.MethodsT3 liposomes (T3-lipo) were prepared using the thin-film hydration method, and their characteristics, including particle size, polydispersity index, zeta potential, encapsulation efficiency, drug loading, drug release, and stability, were evaluated in vitro. We assessed the effect of T3-lipo on hepatocarcinogenesis in diethylnitrosamine (DEN)–induced primary HCC in rats and examined the biodistribution of T3 and T3-lipo by high-performance liquid chromatography–mass spectrometry. Furthermore, we explored the potential molecular mechanism of T3-lipo in hepatocarcinogenesis by immunohistochemistry and immunofluorescence analyses, Bio-Plex assays, real-time polymerase chain reaction analysis, and Western blotting assays.ResultsCompared with T3, T3-lipo had an enhanced inhibitory effect on hepatocarcinogenesis and reduced cardiac side effects in DEN-induced primary HCC in rats. Mechanistically, T3-lipo were absorbed by hepatic macrophages and regulated the secretion of inflammatory cytokines in macrophages by inhibiting inflammatory signaling pathways.ConclusionsT3-lipo may suppress hepatocarcinogenesis by regulating the inflammatory microenvironment in the liver and reduce the cardiac side effects meanwhile.

To further emphasize the clinical–genetic features and prognosis of CDKN2A/B deletions in childhood acute lymphoblastic leukemia (ALL), we retrospectively analyzed 819 consecutive B-ALL patients treated with the Chinese Children’s Cancer Group ALL-2015 (CCCG-ALL-2015) protocol, and fluorescence in situ hybridization (FISH) analysis on CDKN2A/B deletion was available for 599 patients. The prevalence of CDKN2A/B gene deletions was 20.2% (121/599) of B-ALL. CDKN2A/B deletions were significantly associated with older age, higher leukocyte counts, a higher percentage of hepatosplenomegaly, and a higher frequency of BCR-ABL (p < 0.05). Those patients achieved similar minimal residual disease (MRD) clearance and complete remission compared to patients without CDKN2A/B deletion. The CDKN2A/B deletions were correlated with inferior outcomes, including a 3-year event-free survival (EFS) rate (69.8 ± 4.6 vs. 89.2 ± 1.6%, p = 0.000) and a 3-year overall survival (OS) rate (89.4% ± 2.9% vs. 94.7% ± 1.1%, p = 0.037). In multivariable analysis, CDKN2A/B deletion was still an independent prognostic factor for EFS in total cohorts (p < 0.05). We also detected a multiplicative interaction between CDKN2A/B deletions and TP53 deletion on dismal prognosis (p-interaction < 0.05). In conclusion, CDKN2A/B deletion is associated with distinct characteristics and serves as a poor prognostic factor in pediatric ALL, especially in TP53 deletion carriers.