Hypofractionated versus Conventional Postmastectomy Irradiation for Breast Cancer: Comparison of Acute Skin Toxicity.

Purpose: Breast cancer is the leading cause of cancer mortality among women. Radiotherapy can reduce recurrence and prolong survival of patients accepting breast-conserving surgery (BCS). This study aims to compare acute skin reactions in patients receiving hypofractionated versus conventional radiotherapy at a single institution and to summarize the relevant influencing factors. Methods: This study analyzed 152 patients who underwent either hypofractionated or conventional whole-breast irradiation (WBI) after BCS. Acute skin toxicity was assessed according to the Radiation Therapy Oncology Group (RTOG) criteria. Predictive factors for acute skin toxicity were identified using multivariate analysis and visualized using a forest spot. Results: Grade 0 reactions occurred in 75.34% vs 70.89%, grade 1 in 16.44% vs 15.19%, grade 2 in 8.22% vs 12.66%, and grade 3 in 0% vs 1.27% of patients receiving hypofractionated and conventional WBI, respectively. There was no statistically significant difference in acute skin reaction in patients treated with hypofractionated radiation compared with conventional radiation (P = 0.62). Multivariate analysis revealed that metastatic lymph nodes (P = 0.021), whole-breast planning target volume (PTV-WB) (P < 0.001), and tumor bed planning target volume (PTV-TB) (P = 0.002) were significantly correlated with higher rates of acute skin toxicity. Conclusion: Hypofractionated WBI demonstrated similar acute skin adverse reactions compared to conventional WBI. These findings indicate that hypofractionated radiotherapy offers comparable tolerance, equivalent curative effect, convenience, and economic benefits, supporting its clinical promotion.

Targeting DKK1 enhances the antitumor activity of paclitaxel and alleviates chemotherapy-induced peripheral neuropathy in breast cancer.

Chemotherapy in combination with immunotherapy has gradually shown substantial promise to increase T cell infiltration and antitumor efficacy. However, paclitaxel in combination with immune checkpoint inhibitor targeting PD-1/PD-L1 was only used to treat a small proportion of metastatic triple-negative breast cancer (TNBC), and the clinical outcomes was very limited. In addition, this regimen cannot prevent paclitaxel-induced peripheral neuropathy. Therefore, there was an urgent need for a novel target to enhance the antitumor activity of paclitaxel and alleviate chemotherapy-induced peripheral neuropathy in breast cancer. Here, we found that Dickkopf-1 (DKK1) expression was upregulated in multiply subtypes of human breast cancer specimens after paclitaxel-based chemotherapy. Mechanistic studies revealed that paclitaxel promoted DKK1 expression by inducing EGFR signaling in breast cancer cells, and the upregulation of DKK1 could hinder the therapeutic efficacy of paclitaxel by suppressing the infiltration and activity of CD8+ T cells in tumor microenvironment. Moreover, paclitaxel treatment in tumor-bearing mice also increased DKK1 expression through the activation of EGFR signaling in the primary sensory dorsal root ganglion (DRG) neurons, leading to the development of peripheral neuropathy, which is charactered by myelin damage in the sciatic nerve, neuropathic pain, and loss of cutaneous innervation in hindpaw skin. The addition of an anti-DKK1 antibody not only improved therapeutic efficacy of paclitaxel in two murine subtype models of breast cancer but also alleviated paclitaxel-induced peripheral neuropathy. Taken together, our findings providing a potential chemoimmunotherapy strategy with low neurotoxicity that can benefit multiple subtypes of breast cancer patients.

Factors influencing parental fatigue in children with retinoblastoma based on the unpleasant symptoms theory.

Parents of children with retinoblastoma, the most common primary ocular malignant tumour in childhood, bear a heavy caregiving burden and are very susceptible to fatigue. However, little is known about their current status of fatigue and factors influencing fatigue; therefore,this study, based on the theory of unpleasant symptoms, and included 317 parents of children with retinoblastoma in China, whose general demographic data were collected, and on whom the fatigue severity scale (FSS), the generalized anxiety disorder (GAD-7) and 2-item patient health questionnaire (PHQ-2) were administered, from 9 March to 1 June 2020. The parents' FSS score and fatigue incidence were 4.41 ± 1.14 and 67.19%, respectively. The fatigue level was positively correlated with anxiety, depression, education, times of hospitalisations, and treatment types (r = 0.125-0.468, P < 0.05) and negatively correlated with health status, sleep quality, economic status, and family economic situation (r = - 0.120 to - 0.322, P < 0.05). Parent's anxiety level, being an only child and female sex of child influenced parents' fatigue. Healthcare personnel need to focus their attention on this high-risk fatigue group and implement appropriate interventions to reduce their fatigue level, promote their physical and mental health, and facilitate better care for children.

Nurse-led medication management as a critical component of transitional care for preventing drug-related problems.

Drug-related problems (DRPs) are critical medical issues during transition from hospital to home with high prevalence. The application of a variety of interventional strategies as part of the transitional care has been studied for preventing DRPs. However, it remains challenging for minimizing DRPs in patients, especially in older adults and those with high risk of medication discrepancies after hospital discharge. In this narrative review, we demonstrated that age, specific medications and polypharmacy, as well as some patient-related and system-related factors all contribute to a higher prevalence of transitional DPRs, most of which could be largely prevented by enhancing nurse-led multidisciplinary medication reconciliation. Nurses' contributions during transitional period for preventing DRPs include information collection and evaluation, communication and education, enhancement of medication adherence, as well as coordination among healthcare professionals. We concluded that nurse-led strategies for medication management can be implemented to prevent or solve DRPs during the high-risk transitional period, and subsequently improve patients' satisfaction and health-related outcomes, prevent the unnecessary loss and waste of medical expenditure and resources, and increase the efficiency of the multidisciplinary teamwork during transitional care.

Herb pair of Huangqi-Danggui exerts anti-tumor immunity to breast cancer by upregulating PIK3R1.

BACKGROUND: According to traditional Chinese medicine (TCM), drugs supplementing the vital energy, Qi, can eliminate tumors by restoring host immunity. The objective of this study is to investigate the underlying immune mechanisms of anti-tumor activity associated with Qi-supplementing herbs, specifically the paired use of Huangqi and Danggui. METHODS: Analysis of compatibility regularity was conducted to screen the combination of Qi-supplementing TCMs. Using the MTT assay and a transplanted tumor mice model, the anti-tumor effects of combination TCMs were investigated in vitro and in vivo. High content analysis and flow cytometry were then used to evaluate cellular immunity, followed by network pharmacology and molecular docking to dissect the significant active compounds and potential mechanisms. Finally, the anti-tumor activity and the mechanism of the active ingredients were verified by molecular experiments. RESULTS: There is an optimal combination of Huangqi and Danggui that, administered as an aqueous extract, can activate immunity to suppress tumor and is more effective than each drug on its own in vitro and in vivo. Based on network pharmacology analysis, PIK3R1 is the core target for the anti-tumor immunity activity of combined Huangqi and Danggui. Molecular docking analysis shows 6 components of the combined Danggui and Huangqi extract (quercetin, jaranol, isorhamnetin, kaempferol, calycosin, and suchilactone) that bind to PIK3R1. Jaranol is the most important component against breast cancer. The suchilactone/jaranol combination and, especially, the suchilactone/kaempferol combination are key for immunity enhancement and the anti-tumor effects of the extract. CONCLUSIONS: The combination of Huangqi and Danggui can activate immunity to suppress breast cancer and is more effective than the individual drugs alone.

Social support, health behavior self-efficacy, and anxiety on physical activity levels among lung cancer survivors: a structural equation modeling.

PURPOSE: The study aims to investigate the relationship among social support, health behavior self-efficacy, anxiety, and the physical activity (PA) levels of lung cancer survivors, and to analyze whether health behavior self-efficacy and anxiety mediate the relationship between social support and PA levels. METHODS: In a cross-sectional study of 1128 lung cancer survivors from 16 Chinese hospitals, we collected demographic data and administered the Social Support Rating Scale (SSRS), Self-Rated Abilities for Health Practices Scale (SRAHP), Anxiety Scale (AS), and International Physical Activity Questionnaire (IPAQ). SPSS 25.0 was used for descriptive analyses, while the structural equation model in SPSS AMOS 24.0 was used to identify the direct, indirect, and total effects among variables. RESULTS: There were significant correlations among SSRS, SRAHP, AS, and PA (P < 0.01). Model outcomes revealed a positive association between social support and health behavior self-efficacy (ß = 0.732, P < 0.001). Health behavior self-efficacy positively correlated with PA levels (ß = 0.228, P < 0.001) and negatively with anxiety (ß=-0.252, P = 0.001). Moreover, health behavior self-efficacy was found to partially mediate the relationship between social support and PA (ß = 0.174, P < 0.001). CONCLUSIONS AND IMPLICATIONS FOR CANCER SURVIVORS: This study revealed a positive correlation between social support and health behavior self-efficacy, and between health behavior self-efficacy and PA levels among lung cancer survivors. Additionally, health behavior self-efficacy mediated the relationship between social support and PA levels. In future clinical practice, medical and nursing staff should assess social support and health behavior self-efficacy in lung cancer survivors to inform personalized PA interventions.

[A qualitative study on the needs of patients with mandibular defects for occlusal function].

PURPOSE: To understand the current situation and needs of occlusal function exercise in patients with mandibular defects after oral tumor surgery. METHODS： Twenty-seven patients with mandibular defects after oral tumor surgery were interviewed semi-structurally by objective sampling method. The three-level coding system of rooting theory was used for reference, and Nvivo11 qualitative analysis software was used for bottom-up coding analysis. RESULTS: The current situation and needs of occlusal function exercise in patients with mandibular defects can be summarized into five themes, the impact of mandibular defects on patients, lack of knowledge related to occlusal function exercise, demand for content of occlusal function exercise (looking forward to professional health guidance), demand for education methods of occlusal function exercise(expecting diversified education methods and various obstacles to reduce patient compliance). CONCLUSIONS: To establish a unified and standardized program of occlusal function exercise, doctors and nurses should pay attention to various obstacles of patients, adjust the psychological state of patients, and maximize the compliance of patients with occlusal function exercise.

Ghrelin Induces the Production of Hypothalamic NPY Through the AMPK-mTOR Pathway to Alleviate Cancer-induced Bone Pain.

BACKGROUND/AIM: Cancer-induced bone pain (CIBP) is one of the most common symptoms of bone metastasis of tumor cells. The hypothalamus may play a pivotal role in the regulation of CIBP. However, little is known about the exact mechanisms. MATERIALS AND METHODS: First, we established a CIBP model to explore the relationship among hypothalamic ghrelin, NPY and CIBP. Then, we exogenously administered NPY and NPY receptor antagonists to investigate whether hypothalamic NPY exerted an antinociceptive effect through binding to NPY receptors. Finally, we exogenously administered ghrelin to investigate whether ghrelin alleviated CIBP by inducing the production of hypothalamic NPY through the AMPK-mTOR pathway. Body weight, food intake and behavioral indicators of CIBP were measured every 3 days. Hypothalamic ghrelin, NPY and the AMPK-mTOR pathway were also measured. RESULTS: The expression of hypothalamic ghrelin and NPY was simultaneously decreased in cancer-bearing rats, which was accompanied by CIBP. Intracerebroventricular (i.c.v.) administration of NPY significantly alleviated CIBP in the short term. The antinociceptive effect of NPY was reversed with the i.c.v. administration of the Y1R and Y2R antagonists. The administration of ghrelin activated the AMPK-mTOR pathway and induced hypothalamic NPY production to alleviate CIBP. This effect of ghrelin on NPY and antinociception was reversed with the administration of a GHS-R1α antagonist. CONCLUSION: Ghrelin could induce the production of hypothalamic NPY through the AMPK-mTOR pathway to alleviate CIBP, which can provide a novel therapeutic mechanism for CIBP.

Rehabilitation strategies for trismus post oral cancer treatment: Progress in the study of mouth opening exercises.

Oral cancer is a significant public health issue worldwide. Although its treatment methods effectively control tumor growth, they can lead to complications, including Trismus, severely affecting patients' quality of life. The practice standards for mouth opening exercises, a rehabilitative method to prevent and treat Trismus, are not yet clear. Therefore, this article aims to review the research progress of mouth opening exercises in the rehabilitation of Trismus post oral cancer treatment, providing a scientific and effective rehabilitation plan for oral cancer patients to improve their quality of life.

Allicin Overcomes Doxorubicin Resistance of Breast Cancer Cells by Targeting the Nrf2 Pathway.

Breast cancer (BC) is a lethal disorder that threatens the life safety of the majority of females globally, with rising morbidity and mortality year by year. Doxorubicin is a cytotoxic anthracycline antibiotic that is widely used as one of the first-line chemotherapy agents for patients with BC. However, the efficacy of doxorubicin in the clinic is largely limited by its serious side effects and acquired drug resistance. Allicin (diallyl thiosulfinate), as the major component and key active compound present in freshly crushed garlic, has shown potential effects in suppressing chemotherapy resistance in various cancers. Our research aimed to explore the relationship between allicin and doxorubicin resistance in BC. To generate doxorubicin-resistant BC cell lines (MCF-7/DOX and MDA-MB-231/DOX), doxorubicin-sensitive parental cell lines MCF-7 and MDA-MB-231 were continuously exposed to stepwise increased concentrations of doxorubicin over a period of 6 months. CCK-8, colony formation, flow cytometry, RT-qPCR, and western blotting assays were performed to investigate the effects of allicin and/or doxorubicin treatment on the viability, proliferation and apoptosis and the expression of Nrf2, HO-1, phosphate AKT and AKT in doxorubicin-resistant BC cells. Our results showed that combined treatment of allicin with doxorubicin exhibited better effects on inhibiting the proliferation and enhancing the apoptosis of doxorubicin-resistant BC cells than treatment with allicin or doxorubicin alone. Mechanistically, allicin suppressed the levels of Nrf2, HO-1, and phosphate AKT in doxorubicin-resistant BC cells. Collectively, allicin improves the doxorubicin sensitivity of BC cells by inactivating the Nrf2/HO-1 signaling pathway.

Acute Administration of Lactate Exerts Antidepressant-like Effect Through cAMP-dependent Protein Synthesis.

Lactate acts as an important metabolic substrate and signalling molecule modulating neural activities in the brain, and recent preclinical and clinical studies have revealed its antidepressant effect after acute or chronic peripheral administration. However, the neural mechanism underlying the antidepressant effect of lactate, in particular when lactate is acutely administered remains largely unknown. In the current study, we focused on forced swimming test (FST) to elucidate the neural mechanisms through which acute intracerebroventricular (ICV) infusion of lactate exerts antidepressant-like effect. A total of 238 male Sprague Dawley rats were used as experimental subjects. Results showed lactate produced antidepressant-like effect, as indicated by reduced immobility, in a dose- and time-dependent manner. Moreover, the antidepressant-like effect of lactate was dependent of new protein synthesis but not new gene expression, lactate's metabolic effect or hydroxy-carboxylic acid receptor 1 (HCAR1) activation. Furthermore, lactate rapidly promoted dephosphorylation of eukaryotic elongation factor 2 (eEF2) and increased brain-derived neurotrophic factor (BDNF) protein synthesis in the hippocampus in a cyclic adenosine monophosphate (cAMP)-dependent manner. Finally, inhibition of cAMP production blocked the antidepressant-like effect of lactate. These findings suggest that acute administration of lactate exerts antidepressant-like effect through cAMP-dependent protein synthesis.

NUAK1 promotes tumor metastasis through upregulating slug transcription in esophageal squamous cell carcinoma.

BACKGROUND: Metastasis is still a major cause of poor pathological outcome and prognosis in esophageal squamous cell carcinoma (ESCC) patients. NUAK1 has been reported highly expressed in many human cancers and is associated with the poor prognosis of cancer patients. However, the role of NUAK1 and its underlying signaling mechanism in ESCC metastasis remain unclear. METHODS: Expression of NUAK1 in ESCC was detected by real-time quantitative RT-PCR (qRT-PCR), Western blotting and immunohistochemical staining. MTT, colony formation, wound-healing and transwell assays were used to determine the role NUAK1 in vitro. Metastasis was evaluated by use of an experimental pulmonary metastasis model in BALB/c-nu/nu mice. The mechanisms were assessed by using coimmunoprecipitation, immunofluorescence and dual-luciferase reporter gene experiments. RESULTS: NUAK1 was highly expressed in ESCC tissues compared with the adjacent normal esophageal epithelial tissues. Moreover, the elevated expression of NUAK1 positively correlated with tumor invasion depth, lymph node metastasis, pathological TNM stage, and poor survival in ESCC patients. Further experiments showed that NUAK1 overexpression did not change the cell viability and colony formation of ESCC cells, while remarkably promoted the migration and invasion in vitro and experimental pulmonary metastasis in vivo. Mechanistically, NUAK1 enhanced the transcription level of Slug, which enhanced the migratory and invasive capability of ESCC cells. Consistently, silencing Slug almost completely diminished the migration and invasion of NUAK1-overexpressing ESCC cells. Further studies demonstrated that NUAK1 upregulated the transcription activity of Slug through activating the JNK/c-Jun pathway. CONCLUSION: These results demonstrated that NUAK1 promoted the metastasis of ESCC cells through activating JNK/c-Jun/Slug signaling, indicating NUAK1 is a promising therapeutic target for metastatic ESCC.

[Electrophysiological appropriateness technique based on TCM meridian theory for postoperative pain after urethral reconstruction: A real-world study].

OBJECTIVE: To investigate the clinical efficacy of electrophysiological appropriateness technique (EAT) therapy based on the traditional Chinese medicine (TCM) meridian theory in managing postoperative pain after urethral reconstruction surgery. METHODS: Using the real-world study approach, we enrolled 61 male patients undergoing urethral reconstruction and divided them into a control group (n = 30) and an observation group (n = 31), the former receiving patient-controlled intravenous analgesia (PCIA), while the latter PCIA plus EAT at 4 pairs of acupoints (Hegu, Neiguan, Zusanli and Sanyinjiao bilaterally) and the Ashi point, with 100 mg tramadol hydrochloride given orally as remedial analgesia in both groups in case of postoperative Visual Analogue Scale (VAS) score ≥4. We compared the VAS scores at 4, 12, 24 and 48 hours postoperatively, the dose of cumulative fentanyl used at 48 hours, the number of cases needing remedial analgesia, the time to first flatus and the incidence of adverse reactions between the two groups of patients. RESULTS: The VAS scores were markedly lower in the observation than in the control group at 4, 12, 24 and 48 hours after surgery (P < 0.05), with statistically significant differences in time-dependent effect and interactive effect (P < 0.05). Significant reduction was observed in the doses of cumulative fentanyl (P < 0.05) and remedial tramadol analgesia (P < 0.05), time to first flatus (P < 0.05), and incidence of adverse reactions (P < 0.05) in the observation group in comparison with the controls. CONCLUSION: Electrophysiological therapy based on the TCM meridian theory can safely and effectively alleviate postoperative pain after urethral reconstruction, reduce opioid consumption, and decrease adverse events.

Evaluation of Mobile Health Technology Interventions for the Postdischarge Management of Patients With Head and Neck Cancer: Scoping Review.

BACKGROUND: Patients with head and neck cancer (HNC) often experience various types and degrees of complications and functional impairment following surgery or radiotherapy. Consequently, these patients require extensive postdischarge rehabilitation, either at home or in the community. Numerous studies have shown the advantages of mobile Health (mHealth) technology in assisting patients with cancer with self-management and rehabilitation during the postdischarge period. However, few reviews have focused on the intervention, management, and evaluation of mHealth technology in postdischarge patients with HNC. OBJECTIVE: This study aimed to conduct a scoping review of mHealth technology apps and interventions currently available to patients discharged from hospitals after receiving treatment for HNC. This study sought to identify and summarize the types and effectiveness of existing mHealth interventions as well as the differences in their outcome assessments. METHODS: The PubMed, Embase, Web of Science, and CINAHL databases were used to identify studies with no publication time limits. The keywords "mobile health technology" and "head and neck cancer" were combined to address the main concepts of the research questions. RESULTS: Of the 1625 papers identified, 13 (0.8%) met the inclusion and exclusion criteria. Most studies (n=8, 61.5%) were randomized controlled trials (RCTs) and cohort studies. These studies were conducted in 6 countries. The main aims of the mHealth interventions in these studies are as follows: (1) symptom monitoring and assessment, (2) rehabilitation training, (3) access to medical health information, (4) telehealth advisers, (5) peer communication and support, and (6) follow-up/review reminders. The outcome evaluations of the 13 included studies were grouped into 4 categories: (1) technology usability and patient satisfaction, (2) self-management of symptoms and patient-reported outcome-related indicators, (3) adherence, and (4) health-related quality of life. CONCLUSIONS: A limited number of studies have investigated the use of mHealth technology in the postdischarge self-management of patients with HNC. The existing literature suggests that mHealth technology can effectively assist patients with HNC in self-management and postdischarge interventions. It plays an important role in addressing patients' health information needs, reducing both their somatic and psychological burdens, and improving their overall quality of life. Future research should prioritize conducting additional high-quality RCTs to evaluate the usability and analyze the cost-effectiveness of mHealth technology.

Incidence and risk factors of surgical site infection in patients with head and neck cancer: A meta-analysis.

We systematically review the incidence and risk factors of surgical site infection (SSI) in patients with head and neck cancer. PubMed, Embase, Cochrane Library, and Web of Science databases were searched to obtain studies on the risk factors for SSI in patients with HNC. The retrieval time was from the establishment of the database to February 2023. Two reviewers independently screened the literature, extracted data, and assessed the risk of bias in included studies. Meta-analysis was performed by using Stata 15.1 software. A total of 32 articles including 128 919 patients with head and neck cancer and 2949 cases of SSI were included in this meta-analysis. The incidence rate of SSI in head and neck cancer ranges from 19% to 29%, and the overall infection rate was 24%. Meta-analysis indicated that BMI < 20 kg/m2 (OR, 2.64; 95% CI, 1.74-4.00; I2 , 0%), diabetes (OR, 3.00; 95% CI, 2.12-4.16; I2 , 60.6%), ASA score (OR, 1.51; 95% CI, 1.29-1.77; I2 , 0%), radiotherapy (OR, 2.27; 95% CI, 1.87-2.77; I2 , 44.8%), chemotherapy (OR, 2.36; 95% CI, 1.64-3.40; I2 , 0%), clindamycin antibiotic (OR, 2.99; 95% CI, 1.82-2.93; I2 , 36.5%), deficit repair (OR, 3.76; 95% CI, 1.22-11.59; I2 , 91.4%), neck dissection (OR, 2.13; 95% CI, 1.63-2.79; I2 , 16.4%), blood transfusion (OR, 2.29; 95% CI, 1.52-3.45; I2 , 66.2%), mandibular (OR, 3.17; 95% CI, 1.85-5.42; I2 , 73%), tracheostomy (OR, 2.51; 95% CI, 1.74-3.62; I2 , 86.4%), operation time (OR, 1.42; 95% CI, 1.16-1.74; I2 , 86.4%), ALB (OR, 2.48; 95% CI, 1.95-3.15; I2 , 5.3%) were risk factors of surgical site infection in patients with head and neck cancer (p < 0.05). The results of the sensitivity analysis showed good agreement in all risk factors and the results had stability. The present meta-analysis suggests that BMI < 20 kg/m2 , diabetes, ASA score, radiotherapy, chemotherapy, clindamycin antibiotic, deficit repair, neck dissection, blood transfusion, mandibular, tracheostomy, operation time, and ALB were significant risk factors for SSI.

Autologous Fat Grafting for Functional and Aesthetic Improvement in Patients with Head and Neck Cancer: A Systematic Review.

INTRODUCTION: The efficacy and safety of autologous fat grafting for use in oncology patients are controversial. Patients with head and neck cancer have complex anatomy and require reconstructive repair of the head and neck after comprehensive treatment. The limited additional aesthetic and functional studies on the use of autologous fat fillers in patients with head and neck cancer are unclear. This study systematically evaluates the additional function of autologous fat fillers in the head and neck and systematically reviews issues related to autologous fat grafting after comprehensive head and neck cancer treatment, including current indications, techniques, potential complications, graft survival, and patient satisfaction. METHODS: A systematic literature review was performed using PubMed, The Cochrane Library, EMBASE, and Web of Science (last accessed on January 9, 2023). RESULTS: A total of 249 cases of autologous fat fillers in patients with head and neck cancer were reported in 10 clinical publications. Observations were based mainly on subjective physician and patient evaluation indicators, and all studies reported the beneficial effects of autologous fat fillers on aesthetics and function after treatment for head and neck cancer. CONCLUSIONS: Autologous fat fillers are effective in improving the aesthetics and function of head and neck cancer, and due to the limitations of the original study, future studies with large samples are needed to support this. PROSPERO registration number is CRD42020222870. LEVEL OF EVIDENCE III: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Corrigendum: The prevalence of xerostomia among e-cigarette or combustible tobacco users: A systematic review and meta-analysis.

[This corrects the article DOI: 10.18332/tid/156676.].

The prevalence of xerostomia among e-cigarette or combustible tobacco users: A systematic review and meta-analysis.

INTRODUCTION: This study aims to evaluate the prevalence of xerostomia in a healthy population with e-cigarettes and/or combustible tobacco. METHODS: The following electronic databases were searched: Web of Science, Chinese Biomedical Literature Database (CBM), PubMed, Cochrane Library, Embase, Chinese National Knowledge Infrastructure (CNKI), China Science and Technology Journal Database (VIP), and Wan-Fang Database, from 1 January 2000 to 20 October 2022. The language was limited to Chinese and English. The data were analyzed using Stata 15.0, and the prevalence of xerostomia in different smokers is reported. RESULTS: A total of 14 studies were included, with a total sample size of 6827 cases. The overall prevalence of xerostomia was 26% (95% CI: 18-35). In the combustible tobacco population, the prevalence of xerostomia was 24% (95% CI: 21-17), while among e-cigarette users it was 33% (95% CI: 18-48). CONCLUSIONS: Current evidence suggests that the prevalence of xerostomia is high in healthy smoking populations. These findings are restricted by the number and quality of the included studies and need to be validated by additional high-quality studies.

Aucubin enhances the antitumor activity of cisplatin through the inhibition of PD-L1 expression in hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is a leading cause of cancer-associated mortality in the world. However, the anticancer effects of aucubin against HCC have yet to be reported. Cisplatin often decreased CD8+ tumor-infiltrating lymphocytes in the tumor microenvironment through increasing programmed death-ligand 1 (PD-L1) expression, which seriously affected the prognostic effect of cisplatin in the treatment of patients with HCC. Therefore, it is necessary to identify a novel therapeutic avenue to increase the sensitivity of cisplatin against HCC. PURPOSE: This study aims to evaluate the anti-tumor effect of aucubin on HCC, and also to reveal the synergistic effects and mechanism of aucubin and cisplatin against HCC. STUDY DESIGN AND METHODS: An H22 xenograft mouse model was established for the in vivo experiments. Cancer cell proliferation was detected by MTT assay. RT-qPCR was performed to analyze CD274 mRNA expression in vitro. Western blotting was employed to determine the expression levels of the PD-L1, p-Akt, Akt, p-ß-catenin, and ß-catenin in vitro. Immunofluorescence was carried out to examine ß-catenin nuclear accumulation in HCC cells. Immunohistochemistry was used to detect tumoral PD-L1 and CD8α expression in xenograft mouse model. RESULTS: Aucubin inhibits tumor growth in a xenograft HCC mouse model, but did not affect HCC cell viability in vitro. Aucubin treatment significantly inhibited PD-L1 expression through inactivating Akt/ß-catenin signaling pathway in HCC cells. Overexpression of PD-L1 dramatically reversed aucubin-mediated tumoral CD8+ T cell infiltration and alleviated the antitumor activity of aucubin in xenograft mouse model. Moreover, Cisplatin could induce the expression of PD-L1 through the activation of the Akt/ß-catenin signaling pathway in HCC cells, which can be blocked by aucubin in vitro. In xenograft mouse model, cisplatin treatment induced PD-L1 expression and alleviated the infiltration of CD8+ T lymphocytes in the tumor microenvironment. Aucubin not only abrogated cisplatin-induced PD-L1 expression but also enhanced the antitumor efficacy of cisplatin in a mouse xenograft model of HCC. CONCLUSION: Aucubin exerts antitumor activity against HCC and also enhances the antitumor activity of cisplatin by suppressing the Akt/ß-catenin/PD-L1 axis.