A case series on safety and tolerability of human umbilical cord-derived mesenchymal stem cells on patients in Malaysia.

Umbilical cord-derived mesenchymal stem cells for regenerative therapy are a promising treatment option for chronic illnesses. Umbilical cord-derived mesenchymal stem cells offer several advantages over other sources, which makes them an attractive option in tissue repair and regeneration. This clinical study describes a 1-year follow-up on the safety and tolerance of umbilical cord-derived mesenchymal stem cell therapy on nine patients in Malaysia. Patients were assessed for adverse effects, and liver function tests were carried out on both pre- and post-treatments. Umbilical cord-derived mesenchymal stem cells' effectiveness and safety were assessed by follow-up evaluations. All nine patients responded positively towards umbilical cord-derived mesenchymal stem cell therapy, without any adverse effects. After umbilical cord-derived mesenchymal stem cell therapy, a significant improvement was observed in liver functioning test outcomes, as haematological parameters and tumour markers were stable. The present study concludes that umbilical cord-derived mesenchymal stem cell therapy is well tolerated by Malaysian patients; however, further clinical screening must be done over a large number of patients population.

Survival outcomes in HER2-low versus HER2-zero breast cancer after neoadjuvant chemotherapy: a meta-analysis.

BACKGROUND: The survival outcomes in HER2-low versus HER2-zero breast cancer (BC) after neoadjuvant chemotherapy (NACT) remain unclear. The meta-analysis was conducted to summarize current evidence about the survival outcomes in HER2-low versus HER2-zero BC. METHODS: We conducted a systematic search in PubMed and EMBASE databases to identify relevant studies. RESULTS: A total of 14 studies with 53,714 patients were included. Overall, 34,037 patients (63.37%) were HER2-low, and 19,677 patients (36.63%) were HER2-zero. Patients with HER2-low tumors had a significantly lower pathological complete response (pCR) rate than patients with HER2-zero tumors, regardless of the hormone receptor status. Compared with HER2-zero breast cancer, the overall survival (OS) and disease-free survival (DFS) of HER2-low BC were longer in the overall cohort (HR = 0.72; 95% CI = 0.61-0.85; P < 0.0001; HR = 0.83; 95% CI = 0.75-0.92; P = 0.0002); however, no differences were observed in terms of OS and DFS between HER2-low and HER2-zero BC in the HR-negative group. In the HR-positive group, HER2-low status had no significant impact on OS, while significantly associated with increased DFS (HR = 0.85; 95% CI = 0.76-0.96; P = 0.007). CONCLUSION: These results suggest that although HER2-low BC has a poor response to NACT, it is correlated with favorable OS and DFS after NACT in the overall cohort as well as longer DFS in the HR-positive group.

Comparison of the cachexia index based on hand-grip strength (H-CXI) with the original CXI for the prediction of cancer cachexia and prognosis in patients who underwent radical colectomy for colorectal cancer.

Background and aims: The cachexia index (CXI) is a novel biomarker for estimating cancer cachexia. The cachexia index based on hand-grip strength (H-CXI) has been recently developed as a simple proxy for CXI. The present study aims to compare both the H-CXI and CXI for the prediction of cancer cachexia and postoperative outcomes in patients who underwent radical colectomy for colorectal cancer. Methods: Patients who underwent radical operations for colorectal cancer were included in this study. Cancer cachexia was diagnosed according to the international consensus outlined by Fearon et al. The cachexia index (CXI) was calculated as [skeletal muscle index (SMI) × serum albumin/neutrophil-to-lymphocyte ratio (NLR)]. The H-CXI was calculated as [hand-grip strength (HGS)/height2 × serum albumin/NLR]. The SMI was measured based on the preoperative CT images at the third lumbar vertebra (L3) level. HGS was measured before surgery. Results: From July 2014 to May 2021, a total of 1,411 patients were included in the present study, of whom 361 (25.6%) were identified as having cancer cachexia. Patients with cachexia had a lower CXI (p < 0.001) and lower H-CXI (p < 0.001) than those without cachexia. A low CXI but not low H-CXI independently predicted cancer cachexia in the multivariate analysis (OR 1.448, p = 0.024). Both a low CXI (HR 1.476, p < 0.001 for OS; HR 1.611, p < 0.001 for DFS) and low H-CXI (HR 1.369, p = 0.007 for OS; HR 1.642, p < 0.001 for DFS) were independent predictors for overall survival (OS) and disease-free survival (DFS) after adjusting for the same covariates. A low H-CXI but not low CXI was an independent risk factor for postoperative complications (OR 1.337, p = 0.044). No significant association was found between cancer cachexia and postoperative complications. Conclusion: The CXI and H-CXI exhibited better prognostic value than cancer cachexia for the prediction of postoperative outcomes in patients who underwent radical colectomy for colorectal cancer. The H-CXI was a superior index over the CXI in predicting short-term clinical outcomes, whereas the CXI demonstrated a closer correlation with Fearon's criteria for cancer cachexia. Ideal tools for the assessment of cancer cachexia should incorporate not only weight loss but also muscle mass, physical function, and inflammatory state.

A human serum albumin-indocyanine green complex offers improved tumor identification in fluorescence-guided surgery.

Background: Complete tumor removal is critical for achieving a good prognosis in patients but remains challenging for surgeons. Near-infrared fluorescence-guided surgery (NIRFGS) enables surgeons to accurately localize tumors in real time and facilitates accurate resection. Indocyanine green (ICG) has been approved by the U.S. Food and Drug Administration and the National Medical Products Administration for many years. Although the application of ICG has progressed for a variety of surgeries, there are inherent limitations to ICG, including poor water solubility and photostability, short blood half-life, and aggregation in blood, resulting in poor imaging performance. We found that mixing ICG with human serum albumin (HSA) preoperatively and then injecting it can improve the imaging performance. Methods: We prepared fluorescent probes by combining ICG with HSA and identified their optimal ratio via in vitro absorption measurement and emission spectrum characterization of ICG-HSA complex with different mixing ratios and concentration gradients. Subsequently, under the optimal ratio and clinical simulated concentration, we conducted dynamic change analysis of the fluorescence spectral properties after mixing. We then compared the uptake of ICG-HSA in vitro for two different cell types and the imaging performance of different molar ratios of ICG and HSA in mouse models. Results: Through in vitro absorption and emission spectrum characterization of ICG-HSA mixtures with different mixing ratios and concentration gradients, the optimal ratio of the mixture was obtained (ICG:HSA =4:5). Using this ratio, clinical simulated concentration, and mixing, we completed the dynamic change analysis of the fluorescence spectrum properties. The results verified that HSA can improve the dispersion and stability of ICG in aqueous solution, reduce the proportion of free-state ICG, and thus improve the biodistribution. Moreover, the fluorescence performance of ICG was improved. ICG-HSA and ICG uptake in MDA-MB-231 cells and imaging in vivo showed that HSA increased the enrichment of ICG in tumor compared to ICG alone (ICG-HSAfluorescence intensity =237.3±10.7 vs. ICGfluorescence intensity =127.1±10.7). Compared with ICG alone, ICG-HSA provided a clearer tumor boundary and higher tumor-to-background ratio (TBR) (ICG-HSATBRmax 3.49±0.56 vs. ICGTBRmax 1.94±0.23). Conclusions: This study suggests that ICG-HSA can achieve higher tumor-to-background contrast with shorter time and can provide an overall superior imaging performance compared to ICG alone, thus exhibiting considerable potential for clinical application.

Obesity and acute type A aortic dissection: unraveling surgical outcomes through the lens of the upper hemisternotomy approach.

Background: Acute type A aortic dissection (ATAAD) is a pressing cardiovascular emergency necessitating prompt surgical intervention. Obesity, a pervasive health concern, has been identified as a significant risk factor for ATAAD, introducing unique surgical challenges that can influence postoperative outcomes. This study aimed to investigate the outcomes of ATAAD surgery across various body mass index (BMI) categories, focusing on the implications of the upper hemisternotomy (UHS) approach. Methods: Between April 2017 and October 2023, 229 patients diagnosed with ATAAD underwent aortic arch intervention via UHS at the General Hospital of Northern Theater Command. Based on BMI (WS/T 428-2013), patients were categorized into normal weight, overweight, and obese. The primary outcomes included perioperative parameters, intraoperative details, and postoperative complications, with specific emphasis on hypoxemia, defined by the Berlin criteria as a PaO2/FiO2 ratio of ≤300 mmHg. Results: The average age of the cohort was 50.1 ± 11.2 years with a male predominance (174 males). Preoperatively, 49.0% presented with hypoxemia, with the Obese group exhibiting a significantly elevated rate (77.9%, P < 0.001). Postoperatively, while the Normal group demonstrated a lower thoracic drainage volume 24 h post-surgery [180.0 (140.0) ml; P < 0.001], the Obese group indicated prolonged durations for mechanical ventilation and ICU stay, without statistical significance. Unlike the Normal and Overweight groups, the Obese group showed no notable changes in pre- and postoperative PaO2/FiO2 ratio. No significant difference was observed in severe postoperative complications among the groups. Further ROC curve analysis identifies a BMI cutoff of 25.5 for predicting postoperative hypoxemia, with 76.3% sensitivity and 84.4% specificity. And multivariate analysis reveals BMI and preoperative hypoxemia as independent predictors of postoperative hypoxemia. Conclusion: Obesity, although presenting unique challenges in ATAAD interventions, does not necessarily portend adverse outcomes when managed with meticulous surgical planning and postoperative care. The study emphasizes the significance of individualized patient assessment and tailoring surgical strategies, suggesting the potential of UHS in addressing the surgical intricacies posed by obesity in ATAAD patients. Further research is warranted to consolidate these findings.

Prognostic value of GLIM-defined malnutrition in combination with hand-grip strength or gait speed for the prediction of postoperative outcomes in gastric cancer patients with cachexia.

BACKGROUND: Cancer cachexia is associated with impaired functional and nutritional status and worse clinical outcomes. Global Leadership Initiative in Malnutrition (GLIM) consensus recommended the application of GLIM criteria to diagnose malnutrition in patients with cachexia. However, few previous study has applied the GLIM criteria in patients with cancer cachexia. METHODS: From July 2014 to May 2019, patients who were diagnosed with cancer cachexia and underwent radical gastrectomy for gastric cancer were included in this study. Malnutrition was diagnosed using the GLIM criteria. Skeletal muscle index was measured using abdominal computed tomography (CT) images at the third lumbar vertebra (L3) level. Hand-grip strength and 6-meters gait speed were measured before surgery. RESULTS: A total of 356 patients with cancer cachexia were included in the present study, in which 269 (75.56%) were identified as having malnutrition based on the GLIM criteria. GLIM-defined malnutrition alone did not show significant association with short-term postoperative outcomes, including complications, costs or length of postoperative hospital stays. The combination of low hand-grip strength or low gait speed with GLIM-defined malnutrition led to a significant predictive value for these outcomes. Moreover, low hand-grip strength plus GLIM-defined malnutrition was independently associated with postoperative complications (OR 1.912, 95% CI 1.151-3.178, P = 0.012). GLIM-defined malnutrition was an independent predictive factor for worse OS (HR 2.310, 95% CI 1.421-3.754, P = 0.001) and DFS (HR 1.815, 95% CI 1.186-2.779, P = 0.006) after surgery. The addition of low hand-grip strength or low gait speed to GLIM-defined malnutrition did not increase its predictive value for survival. CONCLUSION: GLIM-defined malnutrition predicted worse long-term survival in gastric cancer patients with cachexia. Gait speed and hand-grip strength added prognostic value to GLIM-defined malnutrition for the prediction of short-term postoperative outcomes, which could be incorporated into preoperative assessment protocols in patients with cancer cachexia.

[Short-term Effect of Venetoclax Combined with Azacitidine and "7+3" Regimen in the Treatment of Newly Diagnosed Elder Patients with Acute Myeloid Leukemia].

OBJECTIVE: To compare the short-term effect and adverse reaction of venetoclax (VEN) combined with azacitidine (AZA) versus "7+3" regimen in newly diagnosed elder patients with acute myeloid leukemia (AML). METHODS: From January 2021 to January 2022, the clinical data of seventy-nine newly diagnosed elder patients with AML at the Second Hospital of Shanxi Medical University and the Shanxi Bethune Hospital were retrospectively analyzed, including VEN+AZA group (41 cases) and "7+3" group (38 cases). The propensity score matching(PSM) method was used to balance confounding factors， then response， overall survival(OS), progressionfree survival(PFS) and adverse reactions between the two groups were compared. RESULTS: The ORR of VEN+AZA group and "7+3" group was 68% and 84%, respectively, and the CRc was 64% and 72%, respectively, the differents were not statistically significant (P >0.05). In the VEN+AZA group, there were 5 non-remission (NR) patients, 4 with chromosome 7 abnormality (7q-/-7), and 1 with ETV6 gene mutation. Median followed-up time between the two groups was 8 months and 12 months, respectively, and the 6-months OS was 84% vs 92% (P =0.389), while 6-months PFS was 84% vs 92% (P =0.258). The main hematological adverse reactions in two groups were stage Ⅲ-Ⅳ myelosuppression, and the incidence rate was not statistically different(P >0.05). The median time of neutrophil recovery in two groups was 27(11-70) d, 25(14-61) d （P =0.161）, and platelet recovery was 27(11-75) d, 25(16-50) d （P =0.270）, respectively. The infection rate of VEN+AZA group was lower than that of "7+3" group (56% vs 88%, P =0.012）. The rate of lung infections of two groups was 36% and 64%, respectively, the difference was statistically significant (P =0.048). CONCLUSION: The short-term effect of VEN+AZA group and "7+3" regimens in eldrly AML patients are similar， but the VEN+AZA regimen had a lower incidence of infection. The presence of chromosome 7 abnormality（7q-/-7） may be a poor prognostic factor for elderly AML patients treated with VEN+AZA.

METTL1 mediated tRNA m7G modification promotes leukaemogenesis of AML via tRNA regulated translational control.

BACKGROUND: RNA modifications have been proven to play fundamental roles in regulating cellular biology process. Recently, maladjusted N7-methylguanosine (m7G) modification and its modifiers METTL1/WDR4 have been confirmed an oncogene role in multiple cancers. However, the functions and molecular mechanisms of METTL1/WDR4 in acute myeloid leukemia (AML) remain to be determined. METHODS: METTL1/WDR4 expression levels were quantified using qRT-PCR, western blot analysis on AML clinical samples, and bioinformatics analysis on publicly available AML datasets. CCK-8 assays and cell count assays were performed to determine cell proliferation. Flow cytometry assays were conducted to assess cell cycle and apoptosis rates. Multiple techniques were used for mechanism studies in vitro assays, such as northern blotting, liquid chromatography-coupled mass spectrometry (LC-MS/MS), tRNA stability analysis, transcriptome sequencing, small non-coding RNA sequencing, quantitative proteomics, and protein synthesis measurements. RESULTS: METTL1/WDR4 are significantly elevated in AML patients and associated with poor prognosis. METTL1 knockdown resulted in reduced cell proliferation and increased apoptosis in AML cells. Mechanically, METTL1 knockdown leads to significant decrease of m7G modification abundance on tRNA, which further destabilizes tRNAs and facilitates the biogenesis of tsRNAs in AML cells. In addition, profiling of nascent proteins revealed that METTL1 knockdown and transfection of total tRNAs that were isolated from METTL1 knockdown AML cells decreased global translation efficiency in AML cells. CONCLUSIONS: Taken together, our study demonstrates the important role of METTL1/WDR4 in AML leukaemogenesis, which provides a promising target candidate for AML therapy.

Perceptions of adult patients with cancer towards telemedicine: A qualitative meta-synthesis.

Objective: This study aims to systematically identify, evaluate, and synthesize published qualitative research on the views and attitudes of adult cancer patients toward telemedicine and, consequently to better inform the future development of telemedicine technology and interventions. Methods: A meta-synthesis review was conducted to identify qualitative studies that reported adult cancer patients' perceptions toward telemedicine applications using nine electronic databases, including PubMed, MEDLINE, Web of Science, the Cochrane Library, PsycINFO, CINAHL, Wan Fang, VIP, and CNKI, from inception to November 2022. Quality appraisal was guided by the Joanna Briggs Institute's (JBI) Critical Appraisal Checklist for Qualitative Research. Data were synthesized using "thematic synthesis" to identify themes and concepts. Results: A total of 3518 articles were retrieved, of which 23 met the inclusion and exclusion criteria. These studies identified three key meta-themes and 11 key sub-themes: (1) Benefits of telemedicine: obtaining information and social support, maintaining the continuity of treatment, receiving professional assistance, having greater flexibility, and promoting physical and mental health; (2) Limitations of telemedicine: interference with normal life, privacy and security issues, auxiliary function issues, and increased psychological burden; (3) Expectations for future telemedicine: more personalized intervention, more specific and diverse information. Conclusions: The study showed that the benefits and limitations coexisted in the process of telemedicine application among adult cancer patients. It is necessary to develop personalized applications that are better suited to the needs and characteristics of adult cancer patients. Future telemedicine interventions should focus on information diversification and provide patients with more diverse and effective information. Systematic review registration: PROSPERO, CRD42022324528.

Spatiotemporal development and the regulatory mechanisms of cardiac resident macrophages: Contribution in cardiac development and steady state.

Cardiac resident macrophages (CRMs) are integral components of the heart and play significant roles in cardiac development, steady-state, and injury. Advances in sequencing technology have revealed that CRMs are a highly heterogeneous population, with significant differences in phenotype and function at different developmental stages and locations within the heart. In addition to research focused on diseases, recent years have witnessed a heightened interest in elucidating the involvement of CRMs in heart development and the maintenance of cardiac function. In this review, we primarily concentrated on summarizing the developmental trajectories, both spatial and temporal, of CRMs and their impact on cardiac development and steady-state. Moreover, we discuss the possible factors by which the cardiac microenvironment regulates macrophages from the perspectives of migration, proliferation, and differentiation under physiological conditions. Gaining insight into the spatiotemporal heterogeneity and regulatory mechanisms of CRMs is of paramount importance in comprehending the involvement of macrophages in cardiac development, injury, and repair, and also provides new ideas and therapeutic methods for treating heart diseases.

Sarcopenia predicts postoperative complications and survival in colorectal cancer patients with GLIM-defined malnutrition: Analysis from a prospective cohort study.

OBJECTIVE: To investigate whether sarcopenia could predict postoperative outcomes in patients with colorectal cancer with Global Leadership Initiative on Malnutrition (GLIM)-defined malnutrition. METHODS: Clinical data of patients who underwent radical resection for colorectal cancer were prospectively collected. Sarcopenia was diagnosed by the combination of low handgrip strength and low muscle quantity or quality as measured by abdominal computed tomography (CT) images. Logistic regression analysis and Cox proportional hazards regression analysis were performed to identify independent predictors for postoperative complications and survival, respectively. RESULTS: A total of 310 patients with colorectal cancer with GLIM-defined malnutrition were included, of which 145 (46.77%) were identified with sarcopenia. Malnutritional patients with sarcopenia had significantly higher incidences of total complications (34.5% versus 15.8%), severe complications (9.7% versus 1.8%), longer lengths of postoperative hospital stay (median, 14 days versus 12 days), and more costs (median, 56,257 RMB versus 49,024 RMB) than those without sarcopenia. Sarcopenia was an independent predictive factor for postoperative complications (OR 2.531, 95% CI 1.451-4.415), overall survival (HR 1.519, 95% CI 1.026-2.248), and disease-free survival (HR 1.847, 95% CI 1.324-2.576). Patients with severe sarcopenia had a higher incidence of severe complications but not total complications or survival than those with not-severe sarcopenia. Moreover, the predictive value of sarcopenia for postoperative complications was attributed to muscle strength and quality but not muscle quantity. CONCLUSION: Sarcopenia predicts postoperative complications and survival in patients with colorectal cancer with GLIM-defined malnutrition. Preoperative assessment of sarcopenia is still necessary when nutritional assessment has been well performed.

The Initial Experience of Laparoscopic Management for Type VI Choledochal Cyst in Children.

Purposes: Dilatation of cystic duct is very rare and had been classified as Todani type VI choledochal cyst. Choledochal cyst combined with dilatation of cystic duct is difficult to diagnose preoperatively. The purpose of this study is to report the rare variants and discuss the significance and laparoscopic management strategy in children. Methods: The subjects for this study were 10 consecutive patients with type VI choledochal cyst who had laparoscopic procedures at our institute between January 2009 and January 2023. Laparoscopic cholecystectomy, excision of the dilated cystic duct, and choledochal cyst were carried out, and the continuity of the biliary duct was re-established through a Roux-en-Y hepaticojejunostomy. Results: Cystic duct combined with the common bile duct dilatation was revealed in all the patients intraoperatively. Laparoscopic procedures were completed with no conversions. The postoperative recovery was uneventful. The mean follow-up duration was 27 ± 12.7 months (range 5-36 months) with no postoperative complications encountered. Conclusions: The rare entity of type VI choledochal cyst should be recognized as a distinct type of choledochal cyst and need to be given enough attention clinically. The laparoscopic procedure is a feasible option for experienced surgeons.

Fabrication of Oleophilic Polypeptide Nanoparticle from Complexing of Cross-Linked Epsilon-poly-l-lysine with Docusate Sodium for Preparation of Bactericidal Thermoplastic Polyurethanes.

Thermoplastic polyurethanes (TPUs) are extensively utilized in the biomedical field due to their exceptional mechanical properties and biocompatibility. However, the lack of antibacterial activity limits their application ranges. Nanoscopic particle-based additives with inherent antibacterial characteristics are regarded as promising strategies to prevent biomaterials-associated infection. Herein, a novel polymeric nanoparticle is prepared, which integrates chemically cross-linked epsilon-poly-l-lysine (CPL) and anionic surfactant-docusate sodium (DS). The cross-linked epsilon-poly-l-lysine/docusate sodium (CPL/DS) nanoparticle can be well dispersed in organic solvent and a polymer matrix, which is beneficial to endowing TPUs with synergistic miscibility and antibacterial properties. An antibacterial test showed that the CPL/DS nanoparticles have strong antibacterial activity against S. aureus. Moreover, the results of antibacterial experiments in vitro revealed that almost 100% of S. aureus could be killed by CPL/DS nanoparticle-embedded TPU film with a content of 0.5 wt %. In addition, all of the CPL/DS modified TPU films showed good cytocompatibility in vitro. Consequently, this kind of CPL/DS nanoplatform has great potential to serve as a safe and high-efficient bactericidal agent for endowing biomedical devices with bactericidal property.

Cardioprotective effects of asiaticoside against diabetic cardiomyopathy: Activation of the AMPK/Nrf2 pathway.

Diabetic cardiomyopathy (DCM) is a chronic microvascular complication of diabetes that is generally defined as ventricular dysfunction occurring in patients with diabetes and unrelated to known causes. Several mechanisms have been proposed to contribute to the occurrence and persistence of DCM, in which oxidative stress and autophagy play a non-negligible role. Diabetic cardiomyopathy is involved in a variety of physiological and pathological processes. The 5' adenosine monophosphate-activated protein kinase/nuclear factor-erythroid 2-related factor 2 (AMPK/Nrf2) are expressed in the heart, and studies have shown that asiaticoside (ASI) and activated AMPK/Nrf2 have a protective effect on the myocardium. However, the roles of ASI and AMPK/Nrf2 in DCM are unknown. The intraperitoneal injection of streptozotocin (STZ) and high-fat feed were used to establish the DCM models in 100 C57/BL mice. Asiaticoside and inhibitors of AMPK/Nrf2 were used for intervention. Cardiac function, oxidative stress, and autophagy were measured in mice. DCM mice displayed increased levels of oxidative stress while autophagy levels declined. In addition, AMPK/Nrf2 was activated in DCM mice with ASI intervention. Further, we discovered that AMPK/Nrf2 inhibition blocked the protective effect of ASI by compound C and treatment with ML-385. The present study demonstrates that ASI exerts a protective effect against DCM via the potential activation of the AMPK/Nrf2 pathway. Asiaticoside is a potential therapeutic target for DCM.

The Learning Curve of Total Arch Replacement via Single Upper Hemisternotomy Approach in Aortic Dissection.

Purpose: Upper hemisternotomy (UHS) has benefits over conventional full sternotomy because it ameliorates trauma during cardiac surgery. Owing to its challenging and technically demanding nature, this incision in acute type A aortic dissection (ATAAD) has rarely been reported. This study aimed to analyze the learning curve of total arch replacement (TAR) with moderate hypothermic circulatory arrest via a single UHS approach, which is necessary to guide the training of surgeons in adopting minimally invasive procedures. Patients and Methods: A total of 202 consecutive patients who were definitively diagnosed with ATAAD between July 2016 and June 2021 were enrolled in this retrospective analysis. Patients were divided into three groups based on cumulative sum plots for circulatory arrest time in chronological order. Perioperative characteristics were compared between the groups. Results: There was significant difference in the circulatory arrest time and cross-clamp time respectively among three groups (39.0 min vs 28.0 min vs 15.0 min, P < 0.001; 104.5 min vs 106.2 min vs 84.1 min, P < 0.001). The ventilation time and first 24-h chest tube drainage were statistically different among groups (35.5 h vs 24.0 h vs 19.0 h, P = 0.031; 220.0 mL vs 192.5 mL vs 125.5 mL, P = 0.043). No other clinical outcome was observed as significant difference. Conclusion: A cardiac surgeon can convert a conventional full sternotomy to a single UHS for TAR after experiencing a learning curve, to ensure patient safety. The mastery of this minimally invasive surgical technique may be beneficial for the prognosis of patients with ATAAD.

DSE inhibits melanoma progression by regulating tumor immune cell infiltration and VCAN.

Dermatan sulfate epimerase (DSE) is a C5 epiminase that plays a key role in converting chondroitin sulfate into dermal sulfate. DSE is often upregulated during carcinogenesis of some types of cancer and can regulate growth factor signaling in cancer cells. However, the expression and function of DSE in human melanoma have not been reported. In this study, we investigated the influence of tumor-derived DSE in melanoma progression and the potential mechanism of their action. First, proteomic analysis of collected melanoma tissues revealed that DSE was significantly down-regulated in melanoma tissues. DSE silenced or overexpressed melanoma cells were constructed to detect the effect of DSE on melanoma cells, and it was found that the up-regulation of DSE significantly inhibited the proliferation, migration and invasion of melanoma cells. Data analysis and flow cytometry were used to evaluate the immune subpopulations in tumors, and it was found that the high expression of DSE was closely related to the invasion of killer immune cells. Mechanistically, DSE promoted the expression of VCAN, which inhibited the biological activity of melanoma cells. Together, these results suggest that DSE is downregulated in melanoma tissues, and that high expression of DSE can promote melanoma progression by inducing immune cell infiltration and VCAN expression.

Improving the physicochemical and pharmacokinetic properties of olaparib through cocrystallization strategy.

Olaparib (OLA) is the first PARP inhibitor worldwide used for the treatment of ovarian cancer. However, the oral absorption of OLA is extremely limited by its poor solubility. Herein, pharmaceutical cocrystallization strategy was employed to optimize the physicochemical and pharmacokinetic properties. Four cocrystals of OLA with oxalic acid (OLA-OA), malonic acid (OLA-MA), fumaric acid (OLA-FA) and maleic acid (OLA-MLA) were successfully discovered and characterized. Fourier transform infrared spectroscopy and X-ray photoelectron spectroscopy confirmed the formation of cocrystals rather than salts, and the possible hydrogen bonding patterns were analyzed through molecular surface electrostatic potential calculations. The in vitro and in vivo evaluations indicate that all of the cocrystals demonstrate significantly improved dissolution performance, oral absorption and tabletability compared to pure OLA. Among them, OLA-FA exhibit sufficient stability and the most increased Cmax and AUC0-24h values that were 11.6 and 6.1 times of free OLA, respectively, which has great potential to be developed into the improved solid preparations of OLA.

HPV prevalence and genotype distribution in 2,306 patients with cervical squamous cell carcinoma in central and eastern China.

Background: To explore the positivity rate and genotype distribution of human papillomavirus (HPV) in cervical squamous cell carcinoma (CSCC) tissues in central and eastern China and to provide theoretical basis for cervical cancer screening and prophylactic HPV vaccine development in China. Methods: DNA was extracted from paraffin-embedded tissues of CSCC samples and exfoliated cervical cells of cervical cancer screening populations. 23 HPV genotypes were detected by combining polymerase chain reaction (PCR) and reverse dot hybridized gene chip detection technology in 2,306 CSCC tissues and 10,245 cervical cancer screening populations. The genotype distribution of HPV infection was analyzed. Results: The overall infection rate of HPVs in 2,306 CSCC patients was 92.71%. The frequency of single-type HPV infection and multiple-type HPV infection were 86.48% and 13.51%, respectively. The most common HPV genotypes detected in Chinese CSCC tissues were HPV-16, HPV-18, HPV-31, HPV-33, HPV-45, HPV-52, HPV-58, and HPV-59. The overall positivity rate of these eight high-risk HPV (HR-HPV) genotypes in HPV-positive CSCC was as high as 96.91%. Of which the positivity rate of seven HR-HPV genotypes related to nine-valent HPV vaccines in HPV-positive CSCC was 95.09%. Meanwhile, the overall infection rates of HR-HPV and low-risk HPV (LR-HPV) in female aged 35-64 years who underwent cervical cancer screening were 13.16% and 1.32%, respectively. The high-frequency HR-HPV genotypes in cervical cancer screening women were HPV-52, HPV-58, HPV-16, HPV-53, HPV-68, HPV-39, HPV-51, and HPV-56, with positivity rates of 2.25%, 1.60%, 1.31%, 1.22%, 0.93%, 0.92%, 0.78%, and 0.74%, respectively. Conclusion: Among women screened for cervical cancer in China, detecting the 8 high-frequency HR-HPV genotypes can reduce technical difficulty and reagent costs, while also improving the efficiency and effectiveness of cervical cancer screening. HPV genotyping assists gynecologists in assessing the risk of HR-HPV-positive cervical intraepithelial neoplasia and guiding them in implementing appropriate interventions. Furthermore, HPV genotyping is helpful for doctors to follow up HR-HPV-positive women and to evaluate the protective effect of HPV vaccine.

A LoC-SERS platform based on triple signal amplification for highly sensitive detection of colorectal cancer miRNAs.

In this work, based on a dual signal amplification strategy of enzyme-assisted signal amplification (EASA) and catalytic hairpin assembly (CHA), combined with the magnetic attraction effect, a capillary pump-driven surface-enhanced Raman scattering (SERS) microfluidic chip (LoC-SERS) platform was developed for the sensitive detection of colorectal cancer-associated (CRC) microRNA (miRNA). During the detection process, the miRNA first undergoes an EASA reaction with hairpin DNA1 (hpDNA1) under the action of endonuclease, which generates a large amount of DNA2 cyclically. After that, DNA2 triggers the CHA reaction to proceed, which leads to the ligation of the SERS nanoprobes and the capture nanoprobes (hpDNA2-hpDNA3 complexes). Finally, as the reactant solution flows through the collection zone, the end products are magnetically attracted by the micro-magnets, generating many "hot spots" and leading to a triple amplification of the SERS signal. By quantitative analysis, the platform achieved ultra-low detection limits of miR-122 (4.26 aM) and miR-192 (4.71 aM) within a linear range of 10 aM-10 pM. In addition, the platform's results for clinical samples are highly consistent with those measured by qRT-PCR methods. Overall, the proposed LoC-SERS platform is expected to be an important tool for the early screening of CRC.