Exploring the Median Effective Dose of Ciprofol for Anesthesia Induction in Elderly Patients: Impact of Frailty on ED50.

Purpose: Explore the median effective dose of ciprofol for inducing loss of consciousness in elderly patients and investigate how frailty influences the ED50 of ciprofol in elderly patients. Patients and Methods: A total of 26 non-frail patients and 28 frail patients aged 65-78 years, with BMI ranging from 15 to 28 kg/m2, and classified as ASA grade II or III were selected. Patients were divided into two groups according to frailty: non-frail patients (CFS<4), frail patients (CFS≥4). With an initial dose of 0.3 mg/kg for elderly non-frail patients and 0.25 mg/kg for elderly frail patients, using the up-and-down Dixon method, and the next patient's dose was dependent on the previous patient's response. Demographic information, heart rate (HR), oxygen saturation (SpO2), mean blood pressure (MBP), and bispectral index (BIS) were recorded every 30 seconds, starting from the initiation of drug administration and continuing up to 3 minutes post-administration. Additionally, the total ciprofol dosage during induction, occurrences of hypotension, bradycardia, respiratory depression, and injection pain were recorded. Results: The calculated ED50 (95% confidence interval [CI]) and ED95 (95% CI) values for ciprofol-induced loss of consciousness were as follows: 0.267 mg/kg (95% CI 0.250-0.284) and 0.301 mg/kg (95% CI 0.284-0.397) for elderly non-frail patients; and 0.263 mg/kg (95% CI 0.244-0.281) and 0.302 mg/kg (95% CI 0.283-0.412) for elderly frail patients. Importantly, no patients reported intravenous injection pain, required treatment for hypotension, or experienced significant bradycardia. Conclusion: Frailty among elderly patients does not exert a notable impact on the median effective dose of ciprofol for anesthesia induction. Our findings suggest that anesthesiologists may forego the necessity of dosage adjustments when administering ciprofol for anesthesia induction in elderly frail patients.

CD93 regulates breast cancer growth and vasculogenic mimicry through the PI3K/AKT/SP2 signaling pathway activated by integrin ß1.

In women, breast cancer (BC) accounts for 7%-10% of all cancer cases and is one of the most common cancers. To identify a new method for treating BC, the role of CD93 and its underlying mechanism were explored. MDA-MB-231 cells were used in this study and transfected with si-CD93, si-MMRN2, oe-CD93, si-integrin ß1, or oe-SP2 lentivirus. After MDA-MB-231 cells were transfected with si-NC or si-CD93, they were injected into nude mice by subcutaneous injection at a dose of 5 × 106/mouse to construct a BC animal model. The expression of genes and proteins and cell migration, invasion and vasculogenic mimicry were detected by RT‒qPCR, western blot, immunohistochemistry, immunofluorescence, Transwell, and angiogenesis assays. In pathological samples and BC cell lines, CD93 was highly expressed. Functionally, CD93 promoted the proliferation, migration, and vasculogenic mimicry of MDA-MB-231 cells. Moreover, CD93 interacts with MMRN2 and integrin ß1. Knockdown of CD93 and MMRN2 can inhibit the activation of integrin ß1, thereby inhibiting the PI3K/AKT/SP2 signaling pathway and inhibiting BC growth and vasculogenic mimicry. In conclusion, the binding of CD93 to MMRN2 can activate integrin ß1, thereby activating the PI3K/AKT/SP2 signaling pathway and subsequently promoting BC growth and vasculogenic mimicry.

Association between CORIN promoter methylation and hypertensive disorders of pregnancy - A nested case-control study.

INTRODUCTION: Corin protein and its coding gene variants have been associated with hypertensive disorders of pregnancy (HDP), but the underlying mechanisms are unclear. As a mediator linking fixed genome with the dynamic environment, DNA methylation at the CORIN gene may link corin with HDP but not has been studied. This study aimed to examine whether CORIN promoter methylation and HDP in Chinese pregnant women. METHODS: Based on a cohort of Chinese pregnant women, we designed a nested case-control study including 196 cases with HDP and 200 healthy controls. DNA methylation levels in the CORIN promoter were quantified by pyrosequencing using peripheral blood before 20 gestational weeks. The association between DNA methylation in CORIN promoter and HDP was systemically examined by single CpG association analysis, followed by gene-based analysis. Multiple testing was controlled by the false discovery rate (FDR) method. RESULTS: The single CpG association analysis found that, among the 5 CpG sites assayed, hypermethylation at one CpG site (Chr4:47839945) was significantly associated with HDP (OR = 1.94, raw P = 0.020), but the significance did not survive for multiple testing correction (FDR-P = 0.100). The gene-based association analysis found that DNA methylation of the 5 CpG sites was jointly associated with HDP (raw P = 0.003). In addition to HDP, CORIN promoter methylation was also significantly associated with dynamic blood pressure during pregnancy (raw P < 0.05). DISCUSSION: Hypermethylation in CORIN promoter at early pregnancy was associated with the risk of HDP during late pregnancy in Chinese women. However, further evidence is required to establish the causality between CORIN promoter methylation and HDP.

Effectiveness of perioperative low-dose esketamine infusion for postoperative pain management in pediatric urological surgery: a prospective clinical trial.

BACKGROUND: Postoperative pain is common in pediatric urological surgery. The study assess the impact of perioperative intravenous infusion of low-dose esketamine on postoperative pain in pediatric urological surgery. METHODS: Pediatric patients (n = 80) undergoing urological surgery were randomized into four groups. Patients in the control group were administered an analgesic pump containing only hydromorphone at a dose of 0.1 mg/kg (Hydromorphone Group 1, H1) or 0.15 mg/kg (Hydromorphone Group 2, H2). Patients in the experimental group were injected intravenously with 0.3 mg/kg of esketamine (Esketamine group 1, ES1) or equal volume of saline (Esketamine Group 2, ES2) during anesthesia induction. Esketamine 1.0 mg/kg and hydromorphone 0.1 mg/kg were added to the analgesic pump. Face, Leg, Activity, Crying, and Comfort (FLACC) scale or the Numerical Rating Scale (NRS) and adverse effects were recorded at 2, 6, 24, and 48 h postoperatively. Additionally, total and effective PCA button presses were recorded. RESULTS: In comparison to the H1 group, the pain scores were notably reduced at all postoperative time points in both the ES1 and H2 groups. The ES2 group exhibited lower pain scores only at 24 and 48 h postoperatively. When compared to the H2 group, there were no significant differences in pain scores at various postoperative time points in the ES2 group. However, the ES1 group demonstrated significantly lower pain scores at 6, 24 and 48 h postoperatively, and these scores were also significantly lower than those observed in the ES2 group. The total and effective number of PCA button presses in the ES1, ES2 and H2 group were lower than that in the H1 group (P < 0.001). The incidence of adverse effects within 48 h after surgery was 15% in ES1, 22% in ES2, 58% in H1, and 42% in H2, respectively (P = 0.021). CONCLUSIONS: The use of low-dose esketamine infusion in analgesia pump can effectively alleviates postoperative pain in pediatric urological patients, leading to a significant reduction in the number of analgesic pump button press. The combined approach of perioperative anesthesia induction and analgesia pump administration is recommended for optimal pain management in these patients. TRIAL REGISTRATION: Chinese Clinical Trial Registry- ChiCTR2300073879 (24/07/2023).

Plasma Aß level alterations after sleep deprivation correspond to brain structural remodeling in medical night shift workers.

The relationship between brain structure alteration and metabolic product clearance after night shift work with total sleep deprivation (SD) remains unclear. Twenty-two intensive care unit staff on regularly rotating shift work were implemented with structural and diffusion MRI under both rest wakefulness (RW) and SD conditions. Peripheral blood samples were collected for the measurement of cerebral metabolites. Voxel-based morphometry and diffusion tensor imaging analysis were used to investigate the alterations in the gray matter density (GMD) and mean diffusivity (MD) within the participants. Furthermore, correlation analysis was performed to investigate the relationship between the neuroimaging metrics and hematological parameters. A significant increase in the GMD values was observed in the anterior and peripheral areas of the brain under SD. In contrast, a decrease in the values was observed in the posterior regions, such as the bilateral cerebellum and thalamus. In addition, a significant reduction in the total cerebrospinal fluid volume was observed under SD. The Aß42/Aß40 levels in participants under SD were significantly lower than those under RW. The mean MD increment values extracted from the region of interest (ROI) of the anterior brain were negatively correlated with the increment of plasma Aß42/Aß40 levels (r = -0.658, P = 0.008). The mean GMD decrement values extracted from the posterior ROI were positively correlated with the increment of plasma Aß-40 levels (r = 0.601, P = 0.023). The findings of this study suggest that one night of shift work under SD induces extensive and direction-specific structural alterations of the brain, which are associated with aberrant brain metabolic waste clearance.

Changes of insulin receptors in high fat and high glucose diet mice with insulin resistance.

This study aimed to observe the expression of insulin-signaling molecules in different organs of mice with insulin resistance (IR). Firstly, mice were fed a high-fat and high-sugar diet (HF group) to establish an IR model, and the controls (NF group) were fed with a normal diet. Next, the weight, fasting blood glucose (FBG), serum insulin and insulin tolerance were detected. Pathological changes of liver tissues were observed by H&E staining. The expressions of INSR, IRS-1 and IRS-2 in the liver, skeletal muscle and ovary were measured by qRT-PCR and western blotting. As a result, compared with the NF group, the HF group mice had increased weight, FBG, insulin and IR index after 6-week of feeding as well as a worse performance in the insulin tolerance test and H&E staining showed fatty liver-like changes after 12-week of feeding, exhibited lower expression of INSR, IRS-1 and IRS-2 in the liver of mice at 6 and 12 weeks. The expression of INSR and IRS-1 in skeletal muscle tissues exhibited the same trend, while those in ovary organs showed the opposite trend. These results suggested that the insulin signaling alters in the liver, skeletal muscle and ovary organs with the progress of IR.

Construction and planning application of blue-green ecological network in Ruzhou City based on morphological spatial pattern analysis (MSPA).

Land space planning is an important way to realize the construction of ecological civilization. It is important to improve the ecological service capacity of urban blue-green space during land space planning and combine it with planning strategies. With Ruzhou City from Henan Province as the research area, we constructed the current blue-green ecological network by morphological spatial pattern analysis (MSPA), connectivity analysis and minimum cumulative resistance model, and explored the application of corridor construction in land spatial planning. The results showed that there were seven first-level core patches, which were mainly distributed in the mountain forest space in the southwest and northeast of the city and the belt ecological space formed by Ruhe River in the middle. There were nine second-level core patches. A total of 256 ecological corridors and 135 ecological nodes were screened out. Most of the corridors crossed Ruhe River, so we should focus on protecting Ruhe River and its surrounding environment, providing temporary habitat for biological migration from north to south, improving the stability of overall ecological network, and concerning the restoration of the corridor breakpoints on the west and south sides of the city. It could guide the division of urban development boundaries, and provide scientific basis for the functional orientation and classified management and control of corridors from the perspective of planning.

Increased levels of PD1 and glycolysis in CD4+ T cells are positively associated with lymph node metastasis in OSCC.

BACKGROUND: Cervical lymph node metastasis is one of the poorest prognostic factors in oral squamous cell carcinoma (OSCC). Activated immune cells generally have metabolic abnormalities in the tumour microenvironment. However, it is unknown whether abnormal glycolysis in T cells could facilitate metastatic lymph nodes in OSCC patients. The aim of this study was to investigate the effects of immune checkpoints in metastatic lymph nodes and determine the correlation between glycolysis and immune checkpoint expression in CD4+ T cells. METHODS: Flow cytometry and immunofluorescence staining were used to analyse the differences in CD4+ PD1+ T cells between metastatic lymph nodes (LN+) and negative lymph nodes (LN-). RT‒PCR was performed to detail the expression of immune checkpoints and glycolysis-related enzymes in LN+ and LN-. RESULTS: The frequency of CD4+ T cells decreased in LN+ patients (p = 0.0019). The PD1 expression of LN+ increased markedly compared to that of LN- (p = 0.0205). Similarly, the PD1 of CD4+ T cells in LN+ increased significantly compared to that of LN-. Additionally, glycolysis-related enzyme levels in CD4+ T cells from LN+ patients were dramatically higher than those in LN- patients. PD1 and Hk2 expression in CD4+ T cells was also increased in LN+ OSCC patients with prior surgical treatment compared to those without. CONCLUSIONS: These findings suggest that lymph node metastasis and recurrence in OSCC are associated with increases in PD1 and glycolysis in CD4+ T cells; this response may serve as a potential regulator of OSCC progression.

Effect of Remimazolam on Postoperative Delirium in Older Adult Patients Undergoing Orthopedic Surgery: A Prospective Randomized Controlled Clinical Trial.

Background: Postoperative delirium is common in older adult patients and associated with a poor prognosis. The use of benzodiazepine was identified as an independent risk factor for delirium, but there is no randomized controlled trial regarding the relationship between remimazolam, a new ultra-short acting benzodiazepine, and postoperative delirium. We designed a randomized controlled trial to evaluate if remimazolam increases the incidence of postoperative delirium compared with propofol in older adult patients undergoing orthopedic surgery with general anesthesia. Patients and Methods: We enrolled 320 patients aged more than 60 with American Society of Anesthesiologists physical status I-III who underwent orthopedic surgery. Patients were randomized to two groups to receive intraoperative remimazolam or propofol, respectively. Our primary outcome was the incidence of delirium within 3 days after surgery. Secondary outcome was emergence quality including the incidence of emergence agitation, extubation time, and length of post-anesthesia care unit (PACU) stay. Adverse events were also recorded. Results: The incidence of postoperative delirium was 15.6% in the remimazolam group and 12.4% in the propofol group (Risk ratio, 1.26; 95% CI, 0.72 to 2.21; Risk difference, 3.2%; 95% CI, -4.7% to 11.2%; P = 0.42). No significant differences were observed for time of delirium onset, duration of delirium, and delirium subtype between the two groups. Patients in remimazolam group had a lower incidence of hypotension after induction and consumed less vasoactive drugs intraoperatively, but had a longer postoperative extubation time and PACU stay. Conclusion: General anesthesia with remimazolam was not associated with an increased incidence of postoperative delirium compared with propofol in older adult patients undergoing orthopedic surgery.

Sleep deprivation and recovery sleep affect healthy male resident's pain sensitivity and oxidative stress markers: The medial prefrontal cortex may play a role in sleep deprivation model.

Sleep is essential for the body's repair and recovery, including supplementation with antioxidants to maintain the balance of the body's redox state. Changes in sleep patterns have been reported to alter this repair function, leading to changes in disease susceptibility or behavior. Here, we recruited healthy male physicians and measured the extent of the effect of overnight sleep deprivation (SD) and recovery sleep (RS) on nociceptive thresholds and systemic (plasma-derived) redox metabolism, namely, the major antioxidants glutathione (GSH), catalase (CAT), malondialdehyde (MDA), and superoxide dismutase (SOD). Twenty subjects underwent morning measurements before and after overnight total SD and RS. We found that one night of SD can lead to increased nociceptive hypersensitivity and the pain scores of the Numerical Rating Scale (NRS) and that one night of RS can reverse this change. Pre- and post-SD biochemical assays showed an increase in MDA levels and CAT activity and a decrease in GSH levels and SOD activity after overnight SD. Biochemical assays before and after RS showed a partial recovery of MDA levels and a basic recovery of CAT activity to baseline levels. An animal study showed that SD can cause a significant decrease in the paw withdrawal threshold and paw withdrawal latency in rats, and after 4 days of unrestricted sleep, pain thresholds can be restored to normal. We performed proteomics in the rat medial prefrontal cortex (mPFC) and showed that 37 proteins were significantly altered after 6 days of SD. Current findings showed that SD causes nociceptive hyperalgesia and oxidative stress, and RS can restore pain thresholds and repair oxidative stress damage in the body. However, one night of RS is not enough for repairing oxidative stress damage in the human body.

Association Between Gestational Diabetes Mellitus and the Risks of Type-Specific Cardiovascular Diseases.

Objective: Gestational diabetes mellitus (GDM) has been linked to subsequent overall cardiovascular diseases. However, evidence on the associations of GDM with type-specific cardiovascular diseases is lacking, and findings on the potential impact of type 2 diabetes on the associations are not consistent. This study aimed to explore the associations between GDM and the risks of type-specific cardiovascular diseases. Methods: Data were from 12,025 women (≥20 years) who had delivered at least one live birth in the National Health and Nutrition Examination Survey, 2007-2018. GDM history and type-specific cardiovascular diseases including coronary heart disease (CHD), heart failure and stroke were defined by self-report. We also combined our results with those from previously related publications on the associations between GDM and risks of type-specific cardiovascular diseases with a random-effect model. Results: Compared with women without GDM, the multivariable-adjusted odds ratios (95% confidence intervals) were 1.82 (1.21-2.72) for CHD, 1.43 (0.80-2.53) for heart failure, and 1.19 (0.76-1.86) for stroke among women with a history of GDM. Type 2 diabetes was associated with 43.90, 67.44, and 63.16% of the excess odds of CHD, heart failure and stroke associated with GDM, respectively. Combining results from this study with those from previously related studies yielded odds ratios (95% confidence intervals) of 1.81 (1.60-2.05) for CHD (12 studies, 7,615,322 participants, I2= 72.6%), 1.66 (1.25-2.21) for heart failure (5 studies, 4,491,665 participants, I2= 88.6%), and 1.25 (1.07-1.46) for cerebrovascular disease (9 studies, 6,090,848 participants, I2= 77.8%). Conclusions: GDM showed stronger associations with coronary heart diseases and heart failure than cerebrovascular disease, and the excess risks are attributable, in part, to type 2 diabetes.

A Prospective Evaluation of the Awareness, Knowledge, and Management of Osteoporosis in a Cohort of Medical Staff.

Objective: To investigate the differences in the awareness, knowledge, and management of osteoporosis from a cohort of medical staff after educational intervention. Methods: A total of 653 medical workers from different departments related to the prevention and treatment of osteoporosis from 7 hospitals in Ningxia were enrolled. Information was collected using a designed questionnaire. Results: After 5 years of educational intervention and follow-up, medical staff had an increased understanding of osteoporosis diagnosis, including dual-energy X-ray, ultrasound bone sonometer, fragility fracture history, biochemistry markers, and the awareness of the susceptible population. However, there was no improvement in the cognition of single/dual photo absorptiometry, symptoms and signs, and bone turnover index. Their understanding of antiosteoporosis drugs, especially the application of calcitonin, diphosphates, and vitamin D, was significantly promoted, while the perception of indicators and time in follow-up, some adverse drug reactions, and exercise therapy remained unchanged. Medical staff were remarkably less aware of the management of follow-up for osteoporosis, exercise and diet therapy, and bone turnover markers. Conclusion: A great gap was identified in the perception of osteoporosis among medical staff in the Ningxia region. After the educational intervention, the knowledge regarding some aspects of osteoporosis generally improved. Much more effort should be made to strengthen the training and learning on the special detection methods of osteoporosis, medications and exercise therapy, and follow-up management.

Association Between History of Gestational Diabetes Mellitus and the Risk of Arthritis in Women.

Objective: The association between gestational diabetes mellitus (GDM) and the risk of arthritis has not been reported. GDM increases the risk of long-term complications including diabetes and metabolic syndrome that are positively associated with the risk of arthritis. This study aimed to explore the association between GDM and the risk of arthritis. Methods: Women (age ≥ 20 years) who had delivered at least one live birth were included from the 2007 to 2018 National Health and Nutrition Examination Survey cohort (N = 11,997). Patients who had a history of GDM and arthritis were identified by in-home interview. Subgroup analyses were conducted by arthritis types and status of obesity, current diabetes, metabolic syndrome, smoking, alcohol drinking, and physical activity. Results: GDM was associated with increased odds of arthritis [multivariable-adjusted odds ratio (95% confidence interval): 1.31 (1.06-1.62)], and the result was similar in sensitivity analysis with further adjustment for metabolic syndrome [1.30 (1.05-1.60)]. In subgroup analyses, GDM was associated with increased odds of osteoarthritis [1.47 (1.05-2.06)], while no association was observed with rheumatoid arthritis [1.04 (0.69-1.57)] and other types [1.26 (0.94-1.68)]. GDM was associated with increased odds of arthritis in women without metabolic syndrome [1.34 (1.00-1.78)] and diabetes [1.35 (1.03-1.76)], in obese individuals [1.64 (1.24-2.16)], current/former smokers [1.43 (1.05-1.95)], and current drinkers [1.76 (1.00-3.14)], and in individuals engaging in higher levels of physical activity [1.53 (1.06-2.20)]. Conclusions: GDM was associated with increased odds of arthritis, and the association was independent of type 2 diabetes and metabolic syndrome.

Quality of Recovery After General Anesthesia with Remimazolam in Patients' Undergoing Urologic Surgery: A Randomized Controlled Trial Comparing Remimazolam with Propofol.

Background: Remimazolam is a new medication with sedative and hypnotic effects. It has been demonstrated non-inferior to propofol in general anesthesia with regard to efficacy and safety. However, whether general anesthesia with remimazolam is better than propofol in terms of patients' recovery quality remains unknown. Patients and Methods: Patients enrolled in this study were randomized to remimazolam or propofol group. In remimazolam group, general anesthesia was induced with remimazolam and sufentanil and maintained with remimazolam and remifentanil. In propofol group, general anesthesia was induced with propofol and sufentanil and maintained with propofol and remifentanil. Neuromuscular blocking agent cisatracurium was also injected during anesthesia. Sedation level was monitored by bispectral index (BIS). Our primary outcome was the quality of patients' postoperative recovery, using the Quality of Recovery-15 (QoR-15) scale. Secondary outcomes included SpO2, HR, MBP and frequency of application of vasoactive drugs during anesthesia, as well as incidences of adverse events in the post anesthesia care unit (PACU). Results: The global scores of QoR-15 scale were lower in remimazolam group at postoperative day 1 and day 3 compared to propofol group, but differences between the two groups only had clinical significance at postoperative day 1. Among the five dimensions of QoR-15 scale, scores for physical comfort and emotional state were lower in remimazolam group than propofol group. MBP and HR were higher in remimazolam group than propofol group after anesthesia induction. SpO2 was similar in the two groups. The frequency of application of vasoactive drugs during anesthesia was higher in propofol group than remimazolam group. There was no statistical difference in the incidences of adverse events between the two groups. Conclusion: General anesthesia with remimazolam can provide more stable hemodynamics but also cause temporary reduction in the quality of recovery in patients undergoing urologic surgery, compared to propofol.

Downregulation of Fat Mass and Obesity-Related Protein in the Anterior Cingulate Cortex Participates in Anxiety- and Depression-Like Behaviors Induced by Neuropathic Pain.

N6-methyladenosine (m6A) is the most abundant methylation modification on mRNA in mammals. Fat mass and obesity-related protein (FTO) is the main RNA m6A demethylase. FTO is involved in the occurrence and maintenance of neuropathic pain (NP). NP often induces mental disorders. We found that NP downregulated the expression of FTO in the anterior cingulate cortex (ACC), inhibited the expression of matrix metalloproteinase-9 (MMP-9) in the ACC, maladjusted the brain-derived neurotrophic factor precursor (proBDNF) and mature brain-derived neurotrophic factor (mBDNF) levels in the ACC, and induced anxiety- and depression-like behaviors in mice. Blocking the downregulation of FTO in the ACC induced by peripheral nerve injury could reverse the anxiety- and depression-like behaviors of mice. Contrarily, downregulation of simulated FTO induced anxiety- and depression-like behaviors in mice. After peripheral nerve injury, the binding of FTO to MMP-9 mRNA decreased and the enrichment of m6A on MMP-9 mRNA increased. In conclusion, downregulation of FTO in ACC by regulating MMP-9 mRNA methylation level contributes to the occurrence of anxiety- and depression-like behaviors in NP mice.

Association Between Gestational Diabetes Mellitus and Future Risk of Kidney Stones.

OBJECTIVE: The association between history of gestational diabetes mellitus (GDM) and risk of kidney stones has not been reported. GDM increases the risk of long-term complications including diabetes, hypertension and metabolic syndrome, which are risk factors of kidney stones. This study aimed to explore the association between previous GDM and odds of kidney stones. METHODS: Women (age ≥ 20 years) who had delivered at least one live birth were included from the 2007-2018 National Health and Nutrition Examination Survey cohort (N = 12,003). Patients with kidney stones and history of GDM were identified by in-home interview for all participants. Subgroup analyses were conducted by age, race/ethnicity, postpartum duration and status of hypertension, obesity, current diabetes and metabolic syndrome. RESULTS: Previous GDM was positively associated with odds of kidney stones [multivariate-adjusted odds ratio (95% confidence interval): 1.41 (1.13-1.77)], and the association was stronger with odds of passing 2 or more times of kidney stones [1.72 (1.31-2.26)]. In subgroup analyses, the association between previous GDM and odds of kidney stones was significant in women within 15 years of a pregnancy complicated by GDM [1.54 (1.12-2.11)], in obese participants [1.56 (1.18-2.06)], in women without hypertension [1.49 (1.07-2.08)], current diabetes [1.38 (1.02-1.87)] and metabolic syndrome [1.56 (1.10-2.19)], in women of Non-Hispanic White [1.59 (1.15-2.18)] and in women aged more than 50 year [1.45 (1.02-2.07)]. CONCLUSIONS: Previous GDM was positively associated with odds of kidney stones, and the association was independent of type 2 diabetes, hypertension and metabolic syndrome.

Evaluating the Role of Low Molecular Heparin to Prevent Anterolateral Thigh Flap Compromise in 2460 Head and Neck Defect Cases.

PURPOSE: Since thrombosis is the leading cause of free flap failure, anticoagulant agents appear to improve free flap survival by decreasing the probability of thrombus formation. This retrospective study primarily aimed to evaluate the outcomes and complications of anterolateral thigh flap (ALT) transfer in patients who were postoperatively treated with or without low molecular weight heparin (LMWH) calcium. METHODS: This was a retrospective study. The sample comprised patients who underwent ALT transfer between January 2015 and January 2020 in the Department of Oral and Maxillofacial Surgery at the Second Xiangya Hospital. The predictor variable was LMWH. The outcome variable was flap compromise. Other study variables were age, sex, defect location, hypertension, diabetes, number of vein anastomoses, alcohol history, radiation history, and hematoma. Descriptive, bivariate, and regression statistics were computed, and the P value was set at 0.05. RESULTS: The sample was composed of 2460 patients, comprising 2,234 males and 226 females, with a mean age of 50.5 years (range, 19-79 years). Based on the use of LMWH, the patients were divided into experimental and control groups. There were no significant differences in the clinical characteristics between the groups. Moreover, there were no significant differences in flap compromise or hematoma incidence between the groups. In the logistic regression model for flap compromise, the only factor found to be associated with flap compromise was hematoma (P < .0001). CONCLUSION: The use of LMWH in head and neck free flap transfer does not reduce the incidence of thrombosis and flap compromise.

Intraoperative Intravenous Infusion of Esmketamine Has Opioid-Sparing Effect and Improves the Quality of Recovery in Patients Undergoing Thoracic Surgery: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial.

BACKGROUND: Postoperative thoracic surgery is often accompanied by severe pain, and opioids are a cornerstone of postoperative pain management, but their use may be limited by many adverse events. Several studies have shown that the perioperative application of esketamine adjuvant therapy can reduce postoperative opioid consumption. However, whether esketamine has an opioid-sparing effect after thoracic surgery is unclear. OBJECTIVES: To explore the opioid-sparing effect of different doses of esketamine infusion during thoracic surgery and its impact on patient recovery. STUDY DESIGN: Randomized controlled study. SETTING: A single-center study with a total of 120 patients. METHODS: Patients were randomly allocated to 1 or 3 groups receiving intraoperative intravenous infusions of esketamine 0.15 mg · kg-1· h-1 (group K1), esketamine 0.25 mg · kg-1· h-1(group K2), or placebo (group C). Postoperative opioid consumption, and postoperative indicators like extubation time, PACU stay time, and adverse events were recorded for each group. RESULTS: The consumption of hydromorphone during the first 24 and 48 postoperative hours was significantly reduced in patients of group K2 compared to those of group C and group K1. The time to extubation and post anesthesia care unit (PACU) stay were significantly shorter in group K2 than in group K1 and group C. The time to first feed and off the bed time after surgery were shorter in groups K1 and K2 than in group C. Patients in group K2 were significantly satisfied with patient controlled intravenous analgesia (PCIA) than in groups K1 and C. LIMITATIONS: The sample size calculation was based mainly on the index of hydromorphone consumption. CONCLUSIONS: Intraoperative intravenous esketamine at 0.25 mg · kg-1 · h-1 reduced postoperative opioids consumption by 34% in postoperative 24 hours and 30% in postoperative 48 hours in patients undergoing thoracic surgery. It also improved the quality of perioperative recovery.

Hypoxia-induced ROS promotes mitochondrial fission and cisplatin chemosensitivity via HIF-1α/Mff regulation in head and neck squamous cell carcinoma.

PURPOSE: Chemotherapy based on cisplatin (CDDP) has been established as the treatment of choice for head and neck squamous cell carcinoma (HNSCC). Malignant tumors respond to microenvironmental alterations through a dynamic balance between mitochondrial fission and fusion. HNSCCs are known to exhibit hypoxic conditions, yet the respective effects and underlying mechanisms of hypoxia on chemosensitivity and mitochondrial dynamics remain to be resolved. METHODS: The effect of hypoxia on the chemosensitivity of HNCC cells was determined by flow cytometry. Mitochondrial fission factor (Mff) expression was assessed by RT-PCR and Western blotting in hypoxic HNSCC cells, and further verified in primary CDDP-sensitive and CDDP-resistant HSNCC samples. The biological function of Mff was evaluated by loss of function and gain of function analyses, both in vitro and in vivo. RESULTS: We found that hypoxia promoted mitochondrial fission and CDDP sensitivity in HNSCC cells. Importantly, Mff was found to be correlated with chemosensitivity in primary clinical samples under hypoxic conditions. Hypoxia-inducible factor 1α (HIF-1α) was found to markedly increase Mff transcription and to directly bind to Mff. Hypoxia enhanced the release of reactive oxygen species (ROS) and upregulated the expression of Mff via HIF-1α in HNSCC cells. ROS depletion in HNSCC cells attenuated HIF-1α expression, Mff expression and mitochondrial fission. Moreover, Mff knockdown led to suppression of hypoxia-induced mitochondrial fission and to decreased CDDP chemosensitivity in vivo and in vitro. CONCLUSIONS: Our findings indicate that hypoxia-induced release of ROS can promote mitochondrial fission and CDDP chemosensitivity via HIF1α/Mff regulation in HNSCC cells, indicating that Mff may serve as a biomarker to predict neoadjuvant chemosensitivity in HNSCC patients and as a target for overcoming chemoresistance.

PLAU1 Facilitated Proliferation, Invasion, and Metastasis via Interaction With MMP1 in Head and Neck Squamous Carcinoma.

Head and neck squamous cell carcinoma (HNSCC) is the sixth most common malignant neoplasm; it is associated with high morbidity and mortality. Thus, understanding the molecular mechanisms underlying its initiation and progression is critical for establishing the most appropriate treatment strategies. We found that urokinase-type plasminogen activator (PLAU1) was upregulated and associated with poor prognosis in HNSCC. Silencing of PLAU1 inhibited the proliferation, colony-formation, migration, and invasion abilities of HNSCC cells in vitro and reduced the expression of matrix metalloproteinase 1 (MMP1), whereas PLAU1 overexpression significantly enhanced the growth, the colony-formation, migration, and invasion abilities, and the xenograft tumor growth of HNSCC cells in vivo and increased the expression of MMP1. The Co-IP assay verified that PLAU1 interacted with MMP1. A positive correlation between PLAU1 and MMP1 expression was observed in HNSCC samples. si-RNAs against MMP1 reversed the aggressive effects of PLAU1 overexpression in HNSCC. Taken together, our data revealed that PLAU1 facilitated HNSCC cell proliferation, invasion, and metastasis via interaction with MMP1.