Effects of anesthesia on long-term survival in cancer surgery: A systematic review and meta-analysis.

Backgrounds: The association between anesthesia and long-term oncological outcome after cancer surgery remains controversial. This study aimed to investigate the effect of propofol-based anesthesia and inhalation anesthesia on long-term survival in cancer surgery. Methods: A comprehensive literature search was performed in PubMed, Medline, Embase, and the Cochrane Library until November 15, 2023. The outcomes included overall survival (OS) and recurrence-free survival (RFS). The hazard ratio (HR) and 95 % confidence interval (CI) were calculated with a random-effects model. Results: We included forty-two retrospective cohort studies and two randomized controlled trials (RCTs) with 686,923 patients. Propofol-based anesthesia was associated with improved OS (HR = 0.82, 95 % CI:0.76-0.88, P < 0.00001) and RFS (HR = 0.80, 95 % CI:0.73-0.88, P < 0.00001) than inhalation anesthesia after cancer surgery. However, these positive results were only observed in single-center studies (OS: HR = 0.76, 95 % CI:0.68-0.84, P < 0.00001; RFS: HR = 0.76, 95 % CI:0.66-0.87, P < 0.0001), but not in multicenter studies (OS: HR = 0.98, 95 % CI:0.94-1.03, P = 0.51; RFS: HR = 0.95, 95 % CI:0.87-1.04, P = 0.26). The subgroup analysis revealed that propofol-based anesthesia provided OS and RFS advantages in hepatobiliary cancer (OS: HR = 0.58, 95 % CI:0.40-0.86, P = 0.005; RFS: HR = 0.62, 95 % CI:0.44-0.86, P = 0.005), gynecological cancer (OS: HR = 0.52, 95 % CI:0.33-0.81, P = 0.004; RFS: HR = 0.51, 95 % CI:0.36-0.72, P = 0.0001), and osteosarcoma (OS: HR = 0.30, 95 % CI:0.11-0.81, P = 0.02; RFS: HR = 0.32, 95 % CI:0.14-0.75, P = 0.008) surgeries. Conclusion: Propofol-based anesthesia may be associated with improved OS and RFS than inhalation anesthesia in some cancer surgeries. Considering the inherent weaknesses of retrospective designs and the strong publication bias, our findings should be interpreted with caution. Well-designed multicenter RCTs are still urgent to further confirm these findings.

Accelerometer-measured physical activity, sedentary behavior, and risk of incident pelvic organ prolapse: a prospective cohort study in the UK Biobank.

BACKGROUND: Previous studies on physical activity (PA) and pelvic organ prolapse (POP) were largely limited to self-reported PA in athletes, soldiers, and women in postpartum. We aimed to investigate the association of accelerometer-measured PA and sedentary behavior with the risk of POP in middle-aged and elderly women. METHODS: In this prospective cohort derived from the UK Biobank, the intensity and duration of PA and sedentary behavior were measured with wrist-worn accelerometers over a 7-day period in 2013-2015 for 47,674 participants (aged 42.8-77.9 years) without pre-existing POP. Participants were followed up until the end of 2022, during which incident POP was ascertained mainly by the electronic health records. Multivariable-adjusted Cox proportional hazards models and restricted cubic splines were used to assess the associations of interest. Isotemporal substitution models were applied to test the effects of substituting a type of activity with equivalent duration of others. RESULTS: During a median follow-up of 8.0 years, 779 cases of POP were recorded. The duration of light-intensity PA (LPA) was positively whereas sedentary time was negatively associated with the risk of POP. Every additional 1 h/day of LPA elevated the risk of POP by 18% (95% confidence interval [CI], 10%-26%). In contrast, the risk decreased by 5% (95% CI, 0-8%) per 1 h/day increment in sedentary behavior. No associations were found between moderate-intensity PA (MPA) or vigorous-intensity PA (VPA) and POP, except that women who had a history of hysterectomy were more likely to develop POP when performing more VPA (53% higher risk for every additional 15 min/day). Substituting 1 h/day of LPA with equivalent sedentary time was associated with a 18% (95% CI, 11%-24%) lower risk of POP. The risk can also be reduced by 17% (95% CI, 7%-25%) through substituting 30 min/day of LPA with MPA. CONCLUSIONS: More time spent in LPA or less sedentary time was linked to an elevated risk of POP in middle-aged and elderly women, while MPA or VPA was not. Substituting LPA with equivalent duration of sedentary behavior or MPA may lower the risk of POP.

Gastrodin relieves cognitive impairment by regulating autophagy via PI3K/AKT signaling pathway in vascular dementia.

Vascular dementia (VaD), the second most common type of dementia, is attributed to lower cerebral blood flow. To date, there is still no available clinical treatment for VaD. The phenolic glucoside gastrodin (GAS) is known for its neuroprotective effects, but the role and mechanisms of action on VD remains unclear. In this study, we aim to investigate the neuroprotective role and underlying mechanisms of GAS on chronic cerebral hypoperfusion (CCH)-mediated VaD rats and hypoxia-induced injury of HT22 cells. The study showed that GAS relieved learning and memory deficits, ameliorated hippocampus histological lesions in VaD rats. Additionally, GAS down-regulated LC3II/I, Beclin-1 levels and up-regulated P62 level in VaD rats and hypoxia-injured HT22 cells. Notably, GAS rescued the phosphorylation of PI3K/AKT pathway-related proteins expression, which regulates autophagy. Mechanistic studies verify that YP-740, a PI3K agonist, significantly resulted in inhibition of excessive autophagy and apoptosis with no significant differences were observed in the YP-740 and GAS co-treatment. Meantime, we found that LY294002, a PI3K inhibitor, substantially abolished GAS-mediated neuroprotection. These results revealed that the effects of GAS on VaD are related to stimulating PI3K/AKT pathway-mediated autophagy, suggesting a potentially beneficial therapeutic strategy for VaD.

[Efficacy of volume-targeted ventilation versus high-frequency oscillatory ventilation in the treatment of neonatal respiratory distress syndrome]. / å®¹é‡ç›®æ ‡é€šæ°”ä¸Žé«˜é¢‘æŒ¯è¡é€šæ°”æ²»ç–—æ–°ç”Ÿå„¿å‘¼å¸çª˜è¿«ç»¼åˆå¾çš„ç–—æ•ˆæ¯”è¾ƒ.

OBJECTIVES: To study the clinical efficacy of volume-targeted ventilation (VTV) versus high-frequency oscillatory ventilation (HFOV) in the treatment of neonatal respiratory distress syndrome (NRDS). METHODS: A retrospective cohort analysis was performed on the medical data of 140 neonates with severe NRDS who were admitted from September 2016 to February 2022, with 55 neonates in the VTV group and 85 in the HFOV group. The neonates in the VTV group received conventional mechanical ventilation and target tidal volume, and those in the HFOV group received HFOV. Arterial blood gas parameters were collected at 48 hours after admission, and related indices during hospitalization were recorded, including mortality rate, duration of invasive mechanical ventilation, duration of oxygen therapy, and the incidence rates of complications. RESULTS: Compared with the VTV group, the HFOV group had significantly lower incidence rates of grade Ⅲ-Ⅳ periventricular-intraventricular hemorrhage and neonatal necrotizing enterocolitis (P<0.05), and there were no significant differences between the two groups in the duration of invasive mechanical ventilation, the duration of oxygen therapy, mortality rate, and the incidence rates of bronchopulmonary dysplasia, hypocapnia, hypercapnia, periventricular leukomalacia, and retinopathy of prematurity (P>0.05). CONCLUSIONS: HFOV has a better clinical efficacy than VTV in the treatment of NRDS.

Trends of sphincter-preserving surgeries for low lying rectal cancer: A 20-year experience in China.

Background: Over the last 2 decades, patients with low rectal cancer have had better outcomes from improvements in surgical techniques in sphincter preservation. We aimed to quantify the trends in sphincter-preserving surgeries for low rectal cancer over 20 years in a top tertiary hospital in China. Methods: Between 1999 and 2021, a cohort of patients with primary malignant rectal tumor ≤5cm from the anal verge and who received elective surgeries at Changhai Hospital, Shanghai, China, was identified. Data were extracted from electronic medical records. A Joinpoint Regression Model was used to analyze trends in surgical procedures by average annual percentage change (AAPC). Adjusted Cox proportional hazards regression model was used to assess overall survival. Results: Among a total of 4,172 patients during the study period, 3,111 (74.6%) underwent a sphincter-preserving surgery and 1,061 (25.4%) received APR. Sphincter-preserving surgery increased 3.6% per year (95%CI, 2.3-4.9). Low anterior resection was the most performed procedure (86.3%) and maintained a steady trend, while intersphincteric resection increased 49.4% annually (95%CI, 19.5-86.7) after initiation. Laparoscopic techniques increased 15.1% per year (95%CI, 8.4-43.4) after initiation. Sphincter-preserving surgery increased annually for tumors ≤2cm, 2-≤3cm and 3-≤4cm from the anal verge (AAPC 7.1, 4.5-9.8; 4.7, 3.1-6.3; 2.7, 1.7-3.6, respectively). Furthermore, patients with sphincter-preserving surgery had a better overall survival than abdominoperineal resection (APR) patients (adjusted HR 0.78, 95% CI, 0.65-0.93, p=.01). Conclusions: Utilization of sphincter-preserving surgeries increased significantly over the last 20 years. Patients with low rectal cancer who underwent sphincter preservation had better survival than similar patients who underwent APR.

Risk Factors for Postoperative Pneumonia: A Case-Control Study.

Background: Postoperative pneumonia is a preventable complication associated with adverse outcomes, that greatly aggravates the medical expenses of patients. The goal of our study is to identify risk factors and outcomes of postoperative pneumonia. Methods: A matched 1:1 case-control study, including adult patients who underwent surgery between January 2020 and June 2020, was conducted in the Second Affiliated Hospital of Kunming Medical University in China. Cases included all patients developing postoperative pneumonia within 30 days after surgery, defined using consensus criteria. Controls were selected randomly from the matched eligible population. Results: Out of 17,190 surgical patients, 264 (1.54%) experienced postoperative pneumonia. Increased age, chronic obstructive pulmonary disease, emergency surgery, postoperative reduced albumin, prolonged ventilation, and longer duration of bed rest were identified as significant risk factors independently associated with postoperative pneumonia. Regarding prognostic implications, postoperative pneumonia was associated with longer length of hospital stay, higher ICU occupancy rate, higher unplanned re-operation rate, and higher in-hospital mortality rate. Postoperative pneumonia was most commonly caused by Gram-negative pathogens, and multidrug resistant bacteria accounted for approximately 16.99% of cases. Conclusions: Postoperative pneumonia is associated with severe clinical outcomes. We identified six independent risk factors that can aid in risk stratification and management of patients at risk of postoperative pneumonia, and the distribution of causative pathogens can also help in the implementation of effective interventions. Clinical Trial Registration: www.chictr.org.cn, identifier: chiCTR2100045986.

Successful prolonged cardiopulmonary resuscitation after intraoperative cardiac arrest due to povidone-iodine allergy: A case report.

BACKGROUND: Iodophor (povidone-iodine) is widely used clinically because of its broad-spectrum antibacterial effects. Although extremely rare, it may cause anaphylactic shock, which itself carries the life-threatening risk of cardiac arrest. CASE SUMMARY: We present a case in which a patient with postoperative infection went into anaphylactic shock and cardiac arrest caused by povidone-iodine during secondary surgery. The patient was successfully resuscitated by 2 h of cardiopulmonary resuscitation. CONCLUSION: This is the first known case of cardiac arrest caused by povidone-iodine allergy.

Progress in the study of cancer-associated venous thromboembolism.

OBJECTIVE: Venous thromboembolism is a major cause of morbidity, mortality, and increased medical costs in tumor patients. In the current review, we summarize the progress made in the study of cancer-associated venous thromboembolism. METHODS: By searching cancer-associated venous thromboembolism-related literature on PubMed, the epidemiology, pathological mechanisms, risk factors, risk prediction models, and prevention and treatment of cancer-associated venous thromboembolism were reviewed. RESULTS: The pathophysiological mechanisms of cancer-associated venous thromboembolism are multifactorial. Various blood cell counts (such as platelets and white blood cells) and biomarkers (such as D-dimer and sP-selectin) were considered predictors of thrombosis in cancer patients and were incorporated into the venous thromboembolism risk stratification models. Thromboprophylaxis is currently recommended for all hospitalized cancer patients. In addition, outpatient thromboprophylaxis can be used for selected high-risk patients. Low-molecular-weight heparin was the preferred treatment for cancer-associated venous thromboembolism, but some issues arose in the long-term treatment. In this case, direct oral anticoagulants were a treatment option for tumor patients. The efficacy of direct oral anticoagulant in treating cancer patients is not inferior to low-molecular-weight heparin, but is associated with a higher risk of bleeding. Therefore, there were concerns regarding their safety. CONCLUSION: Since thrombocytopenia, thrombosis recurrence, and bleeding are common in tumor patients, the selection of anticoagulants in this circumstance is a considerable challenge for clinicians.

Potential involvement of Fgf10/Fgfr2 and androgen receptor (AR) in renal fibrosis in adult male rat offspring subjected to prenatal exposure to di-n-butyl phthalate (DBP).

BACKGROUND: We previously demonstrated that maternal exposure to di-n-butyl phthalate (DBP) induces dysplasia of the kidney in newborn male offspring and renal fibrosis in adults. But the underlying mechanisms remain elusive. Fgf10/Fgfr2 and androgen receptor (AR) are known to be important for renal development. We therefore investigated whether these genes are involved in DBP-induced renal fibrosis. MATERIALS AND METHODS: Using Sprague-Dawley rats and rat renal proximal tubular cells (NRK52E), we determined the potential involvement of Fgf10, Fgfr2 and AR in DBP-induced renal fibrosis. RESULTS: We found that maternal exposure to DBP induces renal fibrosis in adult male offspring. A lower serum testosterone concentration and reduced expression of Fgf10, Fgfr2 and AR were detected in these animals. These was a trend toward lower expression of Fgf10, Fgfr2 and AR in NRK52E cells subjected to DBP exposure. Furthermore, higher expression levels of TGF-ß and α-SMA were observed in abnormal renal tissue and DBP-treated NRK52E cells. CONCLUSION: Our findings suggest the potential involvement of Fgf10/Fgfr2 and AR in renal fibrosis of adult male rat offspring induced by prenatal exposure to DBP. The anti-androgenic effects of DBP might play an important role in this pathological process.

DHTKD1 is essential for mitochondrial biogenesis and function maintenance.

Maintaining the functional integrity of mitochondria is crucial for cell function, signal transduction and overall cell activities. Mitochondrial dysfunctions may alter energy metabolism and in many cases are associated with neurological diseases. Recent studies have reported that mutations in dehydrogenase E1 and transketolase domain-containing 1 (DHTKD1), a mitochondrial protein encoding gene, could cause neurological abnormalities. However, the function of DHTKD1 in mitochondria remains unknown. Here, we report a strong correlation of DHTKD1 expression level with ATP production, revealing the fact that DHTKD1 plays a critical role in energy production in mitochondria. Moreover, suppression of DHTKD1 leads to impaired mitochondrial biogenesis and increased reactive oxygen species (ROS), thus leading to retarded cell growth and increased cell apoptosis. These findings demonstrate that DHTKD1 contributes to mitochondrial biogenesis and function maintenance.

Targeted silencing of MART-1 gene expression by RNA interference enhances the migration ability of uveal melanoma cells.

Uveal melanoma (UM) is the most common primary intraocular malignancy and the leading potentially fatal primary intraocular disease in adults. Melanoma antigen recognized by T-cells (MART-1) has been studied extensively as a clinically important diagnostic marker for melanoma, however, its biological function remains unclear. In the present study, the UM cell line SP6.5, which showed a high level of MART-1 expression, was subjected to small interfering RNA-mediated silencing of MART-1. Silencing of MART-1 expression increased the migration ability of SP6.5 cells and down-regulated the expression of the metastasis suppressor NM23. Our results suggest that MART-1 is a candidate target for the development of therapeutic strategies for UM and in particular for the suppression of metastasis associated with this malignancy.

A novel anticancer therapy that simultaneously targets aberrant p53 and Notch activities in tumors.

Notch signaling pathway plays an important role in tumorigenesis by maintaining the activity of self-renewal of cancer stem cells, and therefore, it is hypothesized that interference of Notch signaling may inhibit tumor formation and progression. H101 is a recombinant oncolytic adenovirus that is cytolytic in cells lacking intact p53, but it is unable to eradicate caner stem cells. In this study, we tested a new strategy of tumor gene therapy by combining a Notch1-siRNA with H101 oncolytic adenovirus. In HeLa-S3 tumor cells, the combined therapy blocked the Notch pathway and induced apoptosis in tumors that are p53-inactive. In nude mice bearing xenograft tumors derived from HeLa-S3 cells, the combination of H101/Notch1-siRNA therapies inhibited tumor growth. Moreover, Notch1-siRNA increased Hexon gene expression at both the transcriptional and the translational levels, and promoted H101 replication in tumors, thereby enhancing the oncolytic activity of H101. These data demonstrate the feasibility to combine H101 p53-targted oncolysis and anti-Notch siRNA activities as a novel anti-cancer therapy.

Enhanced therapeutic efficacy of vitamin K2 by silencing BCL-2 expression in SMMC-7721 hepatocellular carcinoma cells.

Vitamin K2 (VK2) exerts cell growth inhibitory effects in various human cancer cells such as SMMC-7721 hepatocellular carcinoma (HCC) cells. BCL-2 is an antiapoptotic protein that is frequently overexpressed in numerous tumors. Modulation of multiple antiapoptotic signaling pathways involving BCL-2, which are related to growth factor-stimulated signal transduction in cell survival, is essential for enhancement of the cytotoxic effect of anticancer drugs. In this study, we tested a new strategy of gene therapy by combining BCL-2 siRNA with VK2. In SMMC-7721 HCC cells, the combined treatment significantly enhanced cytotoxicity compared with treatment with either VK2 or siBCL-2 alone. We found that combined treatment induced a significantly different level of G2 stage inhibition. Furthermore, the p53 protein was overexpressed 24 h subsequent to combination treatment, and p21 was clearly increased at 36 h as a consequence of the increased p53 activity. In conclusion, these data suggest that the antitumor effect of VK2 may be improved by silencing BCL-2 expression in SMMC-7721 HCC cells and provides support for the combined use of VK2 and siBCL-2 as a promising approach in cancer gene therapy.

Connexin 43 interacts with Bax to regulate apoptosis of pancreatic cancer through a gap junction-independent pathway.

Connexins play important roles in many physiological and pathological processes. Although connexins are considered as tumor suppressors in several types of cancer, their roles in pancreatic cancer are unknown. In this study, we found that connexin 43 (Cx43) caused apparent apoptosis and growth inhibition in pancreatic cancer cells. The tumor-suppressive role of Cx43 was independent of the canonical gap junction pathway. In the context of apoptosis, Cx43 translocated to the mitochondria, where it interacted with Bax to initiate the mitochondrial apoptotic pathway. Following further examination of the Cx43 protein, we found that the 241-382aa region of Cx43 was required for interaction with Bax. Furthermore, this region was responsible for permeabilizing mitochondrial membrane potential. The results from the present study elucidate a novel mechanism of the Cx43-mediated regulation of apoptosis in pancreatic cancer.

Differential expression of Mart-1 in human uveal melanoma cells.

Uveal melanoma (UM) is one of the most common primary intraocular malignant tumors in adults. Melanoma antigen recognized by T cell-1 (Mart-1), one of the melanosome-specific proteins, has been widely studied as a marker recognized by cytotoxicity T lymphocytes. Mart-1 is considered to play a critical role in the immunotherapy for melanoma. Additionally, as a biomarker, Mart-1 is often used with other tumor-associated antigens for antidiastole in cutaneous melanoma (CM), uveal melanoma (UM) and nevus. In this study, the differential expression of Mart-1 was investigated in four human UM cells (SP6.5, VUP, OCM-1 and OM431) on three levels of analysis: messenger ribonucleic acid (mRNA), protein and, eventually, morphology. The results revealed that SP6.5 cells had high Mart-1 protein expression while VUP cells had almost none. OCM-1 and OM431 cells produced less Mart-1 than SP6.5 cells according to Western blot analysis, although OM431 cells had the highest expression of Mart-1 mRNA according to real-time PCR. The results indicate the potential use of Mart-1 in the development of therapy for UM.

SP1 suppresses phorbol 12-myristate 13-acetate induced up-regulation of human regucalcin expression in liver cancer cells.

There is a growing evidence that regucalcin (RGN) plays a multifunctional role in liver cancer cells. Previous reports showed that the presence of phorbol 12-myristate 13-acetate (PMA) caused a significant increase in RGN mRNA expression and promoter activity in rat hepatoma cells. In this study, we confirmed that human RGN is also up-regulated by PMA treatment independent of translation, and we identified the mechanism by which PMA up-regulates the expression of human RGN via driving SP1 away from a SP1 motif located within -188/-180 of the promoter in HepG2 cells. Overexpression of SP1 dramatically reduces PMA-induced up-regulation of both internal expression of mRNA and promoter activity, whereas knockdown of SP1 has the opposite effect. Therefore, the present study delineates the fundamental elements in the promoter which will be helpful in the future studies on the regulation of RGN expression in liver cancer.

[Clinical application of three-dimensional reconstruction of CT images in treating mandibular angle hypertrophy].

OBJECTIVE: To investigate the clinical directive significance of three-dimensional reconstruction of CT in treating mandibular angle hypertrophy. METHODS: Between March 2009 and January 2011, 18 patients with mandibular angle hypertrophy were treated using the three-dimensional reconstruction technology of CT. All patients were female, aged 20-36 years with an average of 25 years. Eighteen patients included: 14 single mandibular angle hypertrophy, 3 mandibular angle hypertrophy with masseter hypertrophy, and 1 mandibular angle hypertrophy with bilateral asymmetry; 6 cases of ptosis of mandibular angle, 9 cases of prominent mandibular angle, and 3 cases of introversive mandibular angle. According to the types of mandibular angle hypertrophy, the surgical methods could be correctly chosen. The procedure was planned and simulated; the osteotomy line was marked and the osteotomy was measured on the workstations of three-dimensional reconstruction. RESULTS: No fracture of mandible occurred in the operation. Facial nerve temporary attack occurred in 1 case and recovered at 3 months after operation. All patients were followed up 6-12 months (mean, 7.6 months). After 6 months of operation, the effectiveness was satisfactory in 15 cases, basically satisfactory in 2 cases, and unsatisfactory in 1 case (bilateral asymmetry). CONCLUSION: Based on three-dimensional reconstruction technology of CT, surgical design performed on the model will promote the accuracy of operation. Basically symmetrical appearances can be achieved with satisfactory results.