Based on polydopamine-coated metal organic framework multifunctional nanoplatform for enhanced photothermal/sonodynamicand treatment combined with checkpoint blockade therapy.

To overcome the low efficacy of sonodynamic therapy (SDT) caused by hypoxia in the tumor microenvironment, we developed a multiple anti-tumor nanoplatform with synergistic SDT, photothermal therapy (PTT), and ferroptosis effects. PCN-224@FcCaO2/Mn/dihydroartemisinin/imiquimod/PDA (PFC) was prepared by modified with dihydroartemisinin (DHA), imiquimod (R837), CaO2, ferrocene (Fc) and Mn2+ on the PCN-224 (Cu) to achieve self-replenishment of H2O2/O2 and GSH consumption. FcCaO2 decomposed into H2O2 in the tumor microenvironment, triggering the Fenton effect to produce OH, and Cu2+ reduced the potential loss of OH by the depletion of GSH. Under ultrasonic (US) and laser irradiation, PFC exhibits exciting PTT and SDT effects from polydopamine (PDA) and PCN-224. Mn2+ not only promoted the reaction of H2O2 to produce O2 to effectively enhance SDT but also induced tumor cell apoptosis by Mn2+ combined with DHA. PFC induced ferroptosis via Fe interaction with DHA to produce ROS and reduce the expression of GPX4. The released R837 and tumor-associated antigens from SDT/PTT can produce damage associated molecular patterns (DAMPs), which can initiate adaptive immune responses to kill cancer cells, and released again to promote the tumor immune cycle. What's more, SDT/PTT and ferroptosis combined with aPD-L1 can effectively suppress both primary and distant tumor growth.

PD-L1 expression in recurrent or metastatic head and neck squamous cell carcinoma in China (EXCEED study): a multicentre retrospective study.

AIMS: Programmed death-ligand 1 (PD-L1) is known to be highly expressed in various malignancies, including head and neck squamous cell carcinoma (HNSCC). We aimed to determine the prevalence of PD-L1 expression in recurrent or metastatic HNSCC (R/M HNSCC) among Chinese patients. METHODS: This multicentre, retrospective analysis of data from six centres in China included patients with R/M HNSCC treated from 9 August 2021 to 28 February 2022. PD-L1 expression in tumour tissue was assessed and represented using a combined positive score (CPS). The χ2 and Cochran-Mantel-Haenszel χ2 tests were used to compare the prevalence of different PD-L1 expression statuses according to related co-variables. RESULTS: For all 402 examined patients with R/M HNSCC, 168 cases (41.8%) had PD-L1 expression with a CPS ≥20, and 337 cases (83.8%) had PD-L1 expression with a CPS ≥1. Between the PD-L1 CPS ≥20 group and PD-L1 CPS <20 group, statistically significant differences were observed for variables of sex (p<0.001), smoking habit (p=0.0138 for non-smokers vs current smokers) and primary tumour site (p<0.001 for hypopharynx vs oral cavity and p=0.0304 for larynx vs oral cavity, respectively). CONCLUSION: PD-L1 with CPS ≥20 was expressed in about 41.8% of cases with R/M HNSCC among Chinese patients, and PD-L1 expression was significantly associated with sex, smoking history and primary tumour site. Our findings regarding the variables related to PD-L1 expression level provide insight for clinical practice and a solid basis for future research on immunotherapy in HNSCC. TRIAL REGISTRATION NUMBER: ISRCTN10570964.

Efficacy and safety of pembrolizumab with preoperative neoadjuvant chemotherapy in patients with resectable locally advanced head and neck squamous cell carcinomas.

Background: This study aimed to explore the efficacy and safety of pembrolizumab combined with chemotherapy as neoadjuvant therapy in patients with resectable locally advanced head and neck squamous cell carcinomas (LA-HNSCCs). Methods: In this prospective, single-arm, single-centre clinical trial, patients meeting the inclusion criteria were treated with preoperative neoadjuvant therapy with 200 mg pembrolizumab combined with 75 mg/m2 cisplatin and 175 mg/m2 paclitaxel. This was followed by surgery and postoperative adjuvant therapy. The primary endpoint was the postoperative pathological complete response (pCR) rate. All statistical analyses were performed using SPSS 26. Results: A total of 22 patients were enrolled. The location of primary lesion showed: hypopharynx were 15 (68.2%), oropharynx were 6 (27.3%) and oral cavity was 1 (4.5%). The postoperative pCR rate, was 36.4% (8/22), and there was no delay to surgery due to adverse drug reactions. The rate of laryngeal function preservation was 90.9% (20/22). Delayed wound healing was the main surgical complication, with an incidence of 22.7% (5/22). The median follow-up time was 9.5 months, and only 1 patient (4.55%) suffered a regional recurrence. Conclusion: Preoperative treatment with pembrolizumab and chemotherapy in resectable LA-HNSCC has a high pCR rate with no significant impact on surgical safety. This treatment was found to increase the rate of laryngeal function preservation. However, the effects of neoadjuvant immunotherapy on long-term prognosis in LA-HNSCCs require further study.

Clinicopathological features of incidentally detected metastatic thyroid papillary carcinoma in cervical lymph nodes of non-thyroid cancer patients: a retrospective analysis of 31cases.

BACKGROUND: The incidental finding of thyroid inclusions in lymph nodes of neck dissections of non-thyroid cancer patients is an unusual event. It is still controversial for pathologists about whether this represents benign inclusions or metastatic papillary thyroid carcinoma (PTC). This study is to analyze clinicopathological features of such cases in an attempt to explore their clinical implications. METHODS: Pathological data were searched for incidentally detected PTC of cervical lymph nodes in non-thyroid cancer cases. Clinicopathological characteristics were reevaluated and recorded. BRAF V600E protein expression and sequencing analysis was then performed in cases with sufficient tissues. RESULTS: 31 patients had an incidental finding of PTC in lymph nodes of patients with non-thyroid cancer. BRAF immunohistochemical staining were performed in 17 metastatic lymph nodes with sufficient tumor tissues, and 6 were positive. BRAF V600E point mutation was detected in 5 of 6 BRAF V600E positive cases. Subsequent imaging examinations of the thyroid showed no nodules or calcifications/benign nodules in 20 patients, and suspected malignant nodules in 5 patients. 12 patients underwent total thyroidectomy or ipsilateral lobectomy, and 6 showed PTC in postoperative pathological examinations. The remaining 19 patients without surgery were kept under active surveillance, and no one had recurrence of PTC. CONCLUSION: Incidentally discovered PTC in lymph nodes has usually interpreted as metastasis from a clinical occult thyroid primary cancer, but primary PTC was not always detected. This suggests it could be double occult lesions. With regards to concurrence with highly malignant tumor, most patients could keep regular surveillance.

Clinicopathological practice in the differential diagnosis of mucoepidermoid carcinoma from neoplasms with mucinous component.

Background: The differential diagnosis of mucoepidermoid carcinoma (MEC) from neoplasm undergoing mucinous features brings more pitfalls to pathologists. Combining specific MAML2 gene rearrangement and histological characteristics may be the solution. Methods: Twenty-five tumors with mucinous components were selected for differential diagnosis of MEC. All the cases were detected for MAML2 gene rearrangement. The cases diagnosed as MEC were classified into four variants: classic, oncocytic, Warthin-like, and nonclassified, and they were graded using the Brandwein system. The histological characteristics of non-MECs were summarized for differential diagnosis. Univariate survival analysis was performed on MECs. Results: There were 16 MECs; 62.5% were MAML2 rearranged. For the low-, intermediate-, and high-grade MECs, the rate of rearrangement was 83.3%, 100%, and 28.6%, respectively. Both the oncocytic and Warthin-like MECs were MAML2 rearranged. For the classic and nonclassified MECs without MAML2 rearrangement, non-keratinized squamoid cells and distinctive mucinous cells were essential diagnostic criteria. On survival analysis, all the disease progression occurred in high-grade MECs (p = 0.038). Nine cases were diagnosed as non-MECs: pleomorphic adenoma with mucinous metaplasia showed no ex-capsular involvement; metaplastic Warthin tumor appeared with overt keratinization and residual oncocytic bilayered epithelium; mix squamous cell and glandular papilloma showed an endobronchial papillary growing pattern; adenosquamous carcinoma was accompanied by squamous carcinoma in situ of the overlying mucosa. All the non-MECs were negative for MAML2 rearrangement. Conclusion: The application of combining MAML2 rearrangement and histological characteristics is helpful in the differential diagnosis between MEC and other tumors with mucinous components.

MARCKSL1 interacted with F-actin to promote esophageal squamous cell carcinoma mobility by modulating the formation of invadopodia.

BACKGROUND: Emerging evidence indicates that myristoylated alanine-rich C kinase substrate like 1 (MARCKSL1) is involved in the progression of esophageal squamous cell carcinoma (ESCC). However, the underpinning mechanism is unclear. Here, we investigated the mechanisms involving MARCKSL1 in ESCC progression. METHODS: CCK8, Transwell and wound-healing assays were employed to test the effect of MARCKSL1 on proliferation, invasion and migration in vitro. Next, transcriptome profiling was conducted through RNA sequencing to reveal the underlying mechanism of MARCKSL1 in ESCC progression, which was subsequently verified by western blot and qPCR analysis. Moreover, immunofluorescence and gelatin degradation assays were performed to reveal the ability of MARCKSL1 to mediate invadopodia formation and extracellular matrix (ECM) degradation. Finally, the correlation between MARCKSL1 and the clinicopathological features of ESCC patients was assessed based on TCGA database analysis and immunohistochemistry staining of tissue microarrays. RESULTS: Knockdown of MARCKSL1 markedly attenuated the cell motility capacity of ESCC cells in vitro, while MARCKSL1 overexpression had the opposite effect. Transcriptomic analysis showed that MARCKSL1 mediated the mobility and migration of ESCC cells. In addition, overexpression of MARCKSL1 increased the colocalization of F-actin and cortactin at the frontier edge of migrating cells and ECM degradation. Furthermore, in ESCC patients, the mRNA level of MARCKSL1 in esophageal carcinomas (n = 182) was found to be notably higher than that in adjacent esophageal epithelia (n = 286) and the expression levels of MARCKSL1 in the tumor tissues (n = 811) were significantly increased compared to those in noncancerous esophageal tissues (n = 442) with a large sample size. Higher expression of MARCKSL1 was positively correlated with lymph node metastasis and associated with worse survival rates of patients with ESCC. CONCLUSION: MARCKSL1 promotes cell migration and invasion by interacting with F-actin and cortactin to regulate invadopodia formation and ECM degeneration. High MARCKSL1 expression is positively correlated with poor prognosis in ESCC patients with lymph node metastasis.

A case report of primary colonic paraganglioma with lymph node metastasis.

Background: Paraganglioma is a kind of neuroendocrine tumor that originates from paraganglia outside the adrenal gland. Gastrointestinal tract paraganglioma is very rare and only four cases of paraganglioma originating in the colon have been reported. Case Presentation: We report a case of metastatic paraganglioma originating in the colon, in which the differential diagnosis was established by comprehensively considering clinical information, histology, immunohistochemistry, and findings of fluorescence in situ hybridization and next generation sequencing analyses. The patient has remained well for over 14 months after the treatment. Conclusion: Since all paraganglioma have metastatic potential, we believe that radical surgical resection and regular follow-up are necessary. Genetic testing may be indicative of metastatic potential and prognosis. Because colonic paraganglioma is very rare, differential diagnosis is very important. Our report provides experience for the diagnosis and study of paraganglioma in rare sites.

Forming cytoplasmic stress granules PURα suppresses mRNA translation initiation of IGFBP3 to promote esophageal squamous cell carcinoma progression.

Esophageal squamous cell carcinoma (ESCC) is one of the most fatal malignancies worldwide. Recently, our group identified purine-rich element binding protein alpha (PURα), a single-stranded DNA/RNA-binding protein, to be significantly associated with the progression of ESCC. Additional immunofluorescence staining demonstrated that PURα forms cytoplasmic stress granules to suppress mRNA translation initiation. The expression level of cytoplasmic PURα in ESCC tumor tissues was significantly higher than that in adjacent epithelia and correlated with a worse patient survival rate by immunohistochemistry. Functionally, PURα strongly preferred to bind to UG-/U-rich motifs and mRNA 3´UTR by CLIP-seq analysis. Moreover, PURα knockout significantly increased the protein level of insulin-like growth factor binding protein 3 (IGFBP3). In addition, it was further demonstrated that PURα-interacting proteins are remarkably associated with translation initiation factors and ribosome-related proteins and that PURα regulates protein expression by interacting with translation initiation factors, such as PABPC1, eIF3B and eIF3F, in an RNA-independent manner, while the interaction with ribosome-related proteins is significantly dependent on RNA. Specifically, PURα was shown to interact with the mRNA 3´UTR of IGFBP3 and inhibit its expression by suppressing mRNA translation initiation. Together, this study identifies cytoplasmic PURα as a modulator of IGFBP3, which could be a promising therapeutic target for ESCC treatment.

Mixed large and small cell neuroendocrine carcinoma of the stomach: A case report and review of literature.

BACKGROUND: Gastric neuroendocrine carcinoma (GNEC) is a rare histological subtype of gastric cancer, which is categorized into small cell and large cell neuroendocrine carcinomas. It is characterized by strong invasiveness and poor prognosis. Mixed large and small cell neuroendocrine carcinoma (L/SCNEC) is an extremely rare pathological type of gastric cancer, and there have been no reports on this situation until now. CASE SUMMARY: Herein, we first present a 57-year-old patient diagnosed with L/SCNEC of the stomach. A 57-year-old Chinese male presented with epigastric discomfort. Outpatient gastroscopic biopsy was performed, and pathological examination revealed that the cardia was invaded by adenocarcinoma. The patient underwent laparoscopic-assisted radical proximal subtotal gastrectomy and was diagnosed with L/SCNEC. He refused adjuvant treatment and was followed up every 3 mo. Eight months after the operation, the patient showed no evidence of local recurrence or distant metastasis. CONCLUSION: We advocate conducting further genomic studies to explore the origin of gastric large cell and small cell neuroendocrine carcinoma and using different chemotherapy schemes according to large or small cell neuroendocrine carcinoma of the stomach for clinical research to clarify the heterogeneity of GNEC and improve the prognosis of patients with GNEC.

Deep Learning-Based Recognition of Different Thyroid Cancer Categories Using Whole Frozen-Slide Images.

Introduction: The pathological rare category of thyroid is a type of lesion with a low incidence rate and is easily misdiagnosed in clinical practice, which directly affects a patient's treatment decision. However, it has not been adequately investigated to recognize the rare, benign, and malignant categories of thyroid using the deep learning method and recommend the rare to pathologists. Methods: We present an empirical decision tree based on the binary classification results of the patch-based UNet model to predict rare categories and recommend annotated lesion areas to be rereviewed by pathologists. Results: Applying this framework to 1,374 whole-slide images (WSIs) of frozen sections from thyroid lesions, we obtained an area under a curve of 0.946 and 0.986 for the test datasets with and without WSIs, respectively, of rare types. However, the recognition error rate for the rare categories was significantly higher than that for the benign and malignant categories (p < 0.00001). For rare WSIs, the addition of the empirical decision tree obtained a recall rate and precision of 0.882 and 0.498, respectively; the rare types (only 33.4% of all WSIs) were further recommended to be rereviewed by pathologists. Additionally, we demonstrated that the performance of our framework was comparable to that of pathologists in clinical practice for the predicted benign and malignant sections. Conclusion: Our study provides a baseline for the recommendation of the uncertain predicted rare category to pathologists, offering potential feasibility for the improvement of pathologists' work efficiency.

Complete Response After Pre-Operative Transcatheter Arterial Chemoembolization for Unresectable Primary Hepatic Neuroendocrine Tumour: A Case Report and Literature Review.

Background: Primary hepatic neuroendocrine tumours (PHNET) are extremely rare. Currently, no evidence-based guidelines are available for PHNET treatment, especially for unresectable tumours. Case Presentation: We present the case of a 43-year-old man who was admitted to our hospital with complaints of backache for more than 1 month. The imaging examination showed a 5.5×5.3 cm lesion in the liver and no extrahepatic lesions, which was confirmed as a grade 2 PHNET by the pathological results and exclusion of non-hepatic origins. A multidisciplinary team (MDT) consultation revealed that the lesion was an unresectable primary hepatic neuroendocrine tumour (uPHNET) but could be potentially treated by conversion surgery. The patient was initially administered four cycles of chemotherapy with temozolomide, 5-fluorouracil, and ondansetron, and was evaluated as stable disease (SD) according to the Response Evaluation Criteria in Solid Tumours version 1.1 (RECIST 1.1). Because of the limited clinical benefit of chemotherapy, the patient subsequently underwent transcatheter arterial chemoembolisation (TACE) treatment, which reduced the tumour size and converted uPHNET to resectable tumours. A complete response (CR) was achieved after surgery, and the patient has been disease-free. Conclusions: This case was reported by a patient with uPHNET who benefited from the pre-operative TACE, providing a potentially effective management strategy for refractory tumours.

Serum alpha-fetoprotein as a predictive biomarker for tissue alpha-fetoprotein status and prognosis in patients with hepatocellular carcinoma.

Background: Alpha-fetoprotein (AFP) expression is closely related to hepatocarcinogenesis, and it is an important prognostic factor for hepatocellular carcinoma (HCC). We aimed to investigate the relationship between serum AFP concentration and tissue AFP status and identify the prognostic value of serum and tissue AFP for HCC. Methods: This is a retrospective review of 248 patients with HCC from January 2012 to December 2018. Receiver operating characteristic (ROC) curves were plotted to investigate the predictive value of serum AFP for tissue AFP status. Overall survival (OS) was analyzed using the Kaplan-Meier method and log-rank tests were used for comparison between two groups. Multivariate Cox proportional hazards regression analysis was performed for various risk factors. Results: The serum AFP level in patients with tissue AFP-positive HCC was higher than those with tissue AFP-negative HCC (506.7 vs. 7.7 ng/mL, P<0.0001). Youden's index yielded an optimal cut-off value of serum AFP for tissue AFP status of 92.33 ng/mL with a sensitivity and specificity of 0.84 (95% CI: 0.74-0.90) and 0.88 (95% CI: 0.82-0.92), respectively. Moreover, high serum AFP concentrations (≥92.33 ng/mL) were significantly correlated with positive hepatitis B virus (HBV, P=0.012), tumor size (P=0.025) and histological grade (P=0.001); tissue AFP-positive status was associated with positive HBV (P=0.006), tumor number (P=0.033) and histological grade (P<0.001). Further, serum AFP level ≥92.33 ng/mL and tissue AFP-positive status were associated with poorer OS, and positive HBV (Positive: HR 3.496; 95% CI: 1.349-9.064; P=0.010) and larger tumor size (≥5; HR 2.617; 95% CI: 1.372-4.992; P=0.003) were independent factors of OS. Conclusions: This study showed that serum AFP level could be a highly predictive biomarker for tissue AFP status in patients with HCC. Furthermore, serum AFP levels ≥92.33 ng/mL and tissue AFP-positive status were associated with poorer OS but were not independent factors of OS.

Clinical Significance of the Expression of Co-Stimulatory Molecule B7-H3 in Papillary Thyroid Carcinoma.

Background: B7-H3, also known as CD276, an important immune checkpoint member of the B7-CD28 family, is confirmed as a promising target after PD-L1 in clinical trials. Although the overexpression of B7-H3 has been associated with invasive metastatic potential and poor prognosis in multiple types of cancer, nothing is known regarding the expression profiles of B7-H3 in papillary thyroid carcinoma (PTC). In this study, we carried out a large-scale analysis of B7-H3 expression in PTC patients and evaluated the potential clinical significance of B7-H3. Methods: In total, data from 1,210 samples, including 867 cases from TCGA and four GEO datasets, were collected for B7-H3-related transcriptome analyses, and 343 postoperative, whole-tumor sections were collected from patients with PTC at our institute for B7-H3-specific immunohistochemistry (IHC) staining. The statistical analysis was primarily accomplished using the R project for statistical computing. Results: B7-H3 positivity was found in 84.8% of PTC patients (291/343), and the mRNA and protein expression levels of B7-H3 in PTC were markedly higher than those of para-tumor tissues (p < 0.001), demonstrating that B7-H3 can serve as a potential diagnostic biomarker for PTC. The significant upregulation of B7-H3 in PTC is caused by distinct patterns of CNVs and CpG DNA methylation. Functional enrichment analysis confirmed that high B7-H3 expression was significantly associated with specific immune features and angiogenesis. High B7-H3 protein expression was associated with tumor size (p = 0.022), extrathyroidal extension (ETE) (p = 0.003), and lymph node metastasis (LNM) (p < 0.001). More importantly, multivariate analysis confirmed that B7-H3 was an independent predictor of relapse-free survival (RFS) (p < 0.05). In the subgroup analysis, positive B7-H3 staining was associated with worse RFS in patients with primary tumor size ≥2 cm (p < 0.05), age ≥55 years (p < 0.05), LNM (p = 0.07), multifocality (p < 0.05), and ETE (p < 0.05). In addition, Circos plots indicated that B7-H3 was significantly associated with other immune checkpoints in the B7-CD28 family. Conclusion: This is the first comprehensive study to elucidate the expression profile of B7-H3 in PTC. Our observations revealed that B7-H3 is a novel independent biomarker for predicting LNM and disease recurrence for PTC patients, and it thus may serve as an indicator that could be used to improve risk-adapted therapeutic strategies and a novel target for immunotherapy strategies for patients who undergo an aggressive disease course.

Publication Trends in Rehabilitative Effects of Acupuncture: A Visual Analysis of the Literature.

Objectives: To conduct a comprehensive analysis of scientific outputs in 2011-2021 regarding the rehabilitative effects of acupuncture on diseases. Methods: The study was conducted in the form of knowledge graph and data visualization, with data being drawn from the Web of Science Core Collection database. Results: Articles and reviews were the dominant types; China, Guangzhou University of Chinese Medicine and Medicine ranked was the active country, institution, and journal, respectively, in terms of issued articles. Systematic reviews and the meta-analyses of stroke and pain were extensively carried out in the past decade, whose principal interventions were manual acupuncture, electroacupuncture, scalp acupuncture, and dry needling correspondingly at Baihui (DU20) and Zusanli (ST36). And most frequently utilized rehabilitation assessment criteria were the Fugl-Meyer Assessment Scale and the Barthel Index. More recently, motor function and chronic obstructive pulmonary disease have captured researchers' attention, which might be the futuristic frontier. Conclusions: This article provided a relatively panoramic picture of the scientific outputs in acupuncture for disease rehabilitation, which may help readers embrace the heated topic and grasp the recent research focus on this field.

The first successful treatment and genetic sequencing of primary hepatic adenosarcoma with sarcomatous overgrowth: a case report.

Adenosarcoma is a rare type of tumor with a mixture of epithelial and stromal components and often occurs in the female reproductive system. Primary hepatic adenosarcoma (PHAS) is extremely rare, with only two cases reported so far. Both patients had poor outcomes. Here, we report the case of a 36-year-old man with pain under the xiphoid process who was diagnosed with a bile duct tumor. He was treated with adjuvant radiotherapy when surgery was performed on him. Pathologically, the tumor contained benign epithelial tissue, and the submucosa of the bile duct in the liver showed infiltrating growth of spindle cell components. The cells were dense, mildly heterotypic, and occasionally mitotic, and the patient was diagnosed with PHAS. Whole-exome sequencing results showed that a total of 12 mutations were shared by the two tissues. The patient received adjuvant radiotherapy and he was tumor-free until 31 months postoperatively. This case will provide some references of the disease to other researchers.

Validation of the functional assessment of anorexia/cachexia therapy instrument to assess quality of life in maintenance hemodialysis patients with cachexia.

BACKGROUND: Many patients on maintenance hemodialysis (MHD) eventually suffer from cachexia. The Functional Assessment of Anorexia/Cachexia Therapy (FAACT) is a tool used to evaluate the quality of life of patients with cachexia related to various diseases, but its suitability for use in MHD patients has yet to be verified. This study aimed to explore the validation of the FAACT in MHD patients by conducting reliability and validity tests. METHODS: Qualified MHD patients were selected to complete the FAACT and Kidney Disease Quality of Life Short Form 36 (KDQOL-36) questionnaires, and their demographic data and biochemical test results were collected from electronic medical records. Next, the Cronbach's alpha coefficient, paired sample t test and ICC were used to analyze the scale consistency. Additionally, the association between the KDQOL-36 and FAACT was analyzed using Bland-Altman plots and Pearson correlation analysis. Finally, the patients were divided into groups to evaluate discriminant validity. RESULTS: A total of 299 patients were included in this study. The Cronbach's alpha coefficients of the FAACT and its anorexia-cachexia subscale (ACS) were 0.904 and 0.842, respectively, and their ICC exceeded 0.90. The correlation coefficients between the FAACT and its items ranged from 0.146 to 0.631, and the correlation coefficients between the FAACT and KDQOL-36 dimensions ranged from 0.446 to 0.617. The Bland-Altman plots between the FAACT and KDQOL-36 showed that only 3.3% of the points were outside the 95% limits of agreement. The effects of cachexia status (present or absent) on FAACT and ACS scores had effect sizes of 0.54 (P < 0.001) and 0.60 (P < 0.001), respectively. The FAACT and ACS also significantly discriminated between patients with and without inflammation (P < 0.001). CONCLUSIONS: The FAACT and ACS have acceptable reliability and validity in MHD patients and are suitable for measuring the quality of life of MHD patients with cachexia.

Tumor-stroma TGF-ß1-THBS2 feedback circuit drives pancreatic ductal adenocarcinoma progression via integrin αvß3/CD36-mediated activation of the MAPK pathway.

The pancreatic ductal adenocarcinoma (PDAC) microenvironment contains dense desmoplastic stroma dominated by cancer-associated fibroblasts (CAFs) and is crucial to cancer development and progression. Several studies have revealed that thrombospondin 2 (THBS2) is a valuable serological-marker in PDAC. However, the detailed mechanism of the cancer-stroma interactome remains unclear. Here we showed that elevated THBS2 expression in PDAC was predominantly restricted to stroma and correlated with tumor progression and poor prognosis by quantitative proteomics and immunohistochemistry analyses. RNA in situ hybridization confirmed that CAFs but not neoplastic cells expressed THBS2 in precancerous lesions and its levels gradually increased with disease progression in genetically engineered mouse models. Mechanistically, cancer cell-secreted TGF-ß1 activated CAFs to induce THBS2 expression via the p-Smad2/3 pathway. Consequently, CAF-derived THBS2 bound to the membrane receptors integrin αvß3/CD36 and activated the MAPK pathway in PDAC cells to promote tumor growth and adhesion in vitro and in vivo. Inhibition of integrin αvß3, CD36, MEK and JNK rescued THBS2-induced malignant phenotypes. In conclusion, the TGF-ß1-THBS2-integrin αvß3/CD36-MAPK cascade forms a complex feedback circuit to mediate reciprocal interactions of pancreatic cancer cells-CAFs. THBS2 may act as a novel therapeutic-target to block the cancer-stroma communication.

Combination of Chinese medicinal formulas and chemotherapy for triple-negative breast cancer strengthens body resistance to eliminate pathogenic factors.

BACKGROUND: To evaluate the efficacy and safety of strengthening the body's resistance to eliminate pathogenic factors in Chinese medicinal formulas combined with chemotherapy (hereafter referred to as combined therapy [CT]) in triple-negative breast cancer. METHODS: By searching the 7 electronic databases, PubMed, EMBASE, Web of Science, Cochrane Library, Chinese Academic Journal, Wanfang Database, and Chinese Science and Technology Journal, from the beginning of the establishment to April 2022 to identify eligible randomized controlled trial studies. RESULTS: The meta-analysis showed that compared with chemotherapy, CT can effectively improve the objective remission rate (risk ratio [RR]: 1.39; 95% confidence interval [CI]: 1.28, 1.52; P < .00001, I2 = 3%), reduce the recurrence rate (RR: 0.33; 95% CI: 0.14, 0.78; P = .01, I2 = 0%) metastasis rate (RR: 0.48; 95% CI: 0.31, 0.73; P = .0006, I2 = 0%) and the incidence of toxic and side reactions, lower tumor marker levels, regulated T lymphocyte subset changes, and increased average progression-free survival (standardized mean difference: 2.78; 95% CI: 1.41, 4.14; P < .0001, I2 = 97%), and improve the quality of life (RR: 1.55; 95% CI: 1.21, 1.99; P = .0005, I2 = 52%). CONCLUSION: This study suggests that CT appears to be an effective and safe treatment approach. Although this conclusion requires further confirmation owing to insufficient quality of the included trials.

Long-term survival of a patient with pancreatic cancer and lung metastasis: A case report and review of literature.

BACKGROUND: Pancreatic cancer (PC) is a leading cause of cancer-related death, given its poor prognosis and the limited benefits of traditional therapies. As tumors become more genetically disorganized as they progress, genetic mutations might become new markers for us to predict their behavior. Nowadays, many inhibitors can selectively target gene products as a form of targeted therapy, with some showing promise as treatment for various types of cancer. CASE SUMMARY: We describe a rare case of a PC patient with long-term survival of more than 8 yr. The patient was diagnosed with pancreatic ductal adenocarcinoma (PDAC) with BAP1 and PIK3CA gene mutations and Raf1 fusion and achieved partial response twice after treatment with apatinib in combination with chemotherapy. CONCLUSION: BAP1, PIK3CA mutations, and Raf1 fusion are rare in PDAC. Patients with these three gene alterations of PDAC may achieve long-term survival with apatinib. Further research in other contexts is needed to determine whether apatinib has ideal efficacy for PC treatment.

Effectiveness of Acupuncture on Urinary Retention: A Meta-Analysis.

OBJECTIVES: This study aimed to evaluate the safety and efficacy of acupuncture in the treatment of urinary retention (UR). METHODS: Randomized controlled trials investigating the effectiveness of acupuncture in the treatment of UR were identified by searching seven comprehensive databases (Cochrane Library, PubMed, Embase, China National Knowledge Infrastructure, Wanfang Database, China Science and Technology Journal Database, and Chinese Biomedical Literature Database) prior to September 2020. Data analysis was performed using RevMan, version 5.3, and Stata software, version 14.0. RESULTS: A total of 12 studies with 979 participants were included. A random-effects model was used to conduct a meta-analysis on the acupuncture group and the control group. The results show that acupuncture can effectively promote spontaneous urination and reduce anxiety in patients with poor urination (relative risk: 1.35; 95% confidence interval (CI): 1.19-1.53; P < 0.00001). The random-effects model showed significant differences in residual urine volume between the acupuncture group and the control group (MD: -84.79, 95% CI: -135.62 to -33.94; P=0.001). CONCLUSION: Acupuncture is safe and effective in the treatment of UR. However, since the current level of evidence is limited, high-quality, large-sample, multi-center, clinical randomized controlled trials are needed to further confirm our conclusions in the future.