[Effect of asiaticoside on systolic blood pressure and relaxation of isolated thoracic aorta of rats].

OBJECTIVE: To investigate the effect of asiaticoside on blood pressure and relaxation of thoracic aorta in rats and explore the underlying mechanism. METHODS: SD rats treated with 50 and 100 mg/kg asiaticoside by daily gavage for 2 weeks were monitored for systolic blood pressure changes, and histological changes of the thoracic aorta were evaluated using HE staining. In isolated rat endothelium-intact and endothelium-denuded thoracic aorta rings, the effects of asiaticoside on relaxation of the aortic rings were tested at baseline and following norepinephrine (NE)- and KCl-induced constriction. The vascular relaxation effect of asiaticoside was further observed in NE-stimulated endothelium-intact rat aortic rings pretreated with L-nitroarginine methyl ester, indomethacin, zinc protoporphyrin Ⅸ, tetraethyl ammonium chloride, glibenclamide, barium chloride, Iberiotoxin, 4-aminopyridine, or TASK-1-IN-1. The aortic rings were treated with KCl and NE followed by increasing concentrations of CaCl2 to investigate the effect of asiaticoside on vasoconstriction induced by external calcium influx and internal calcium release. RESULTS: Asiaticoside at 50 and 100 mg/kg significantly lowered systolic blood pressure in rats without affecting the thoracic aorta histomorphology. While not obviously affecting resting aortic rings with intact endothelium, asiaticoside at 100 mg/kg induced significant relaxation of the rings constricted by KCl and NE, but its effects differed between endothelium-intact and endothelium-denuded rings. In endothelium-intact aortic rings pretreated with indomethacin, ZnPP Ⅸ, barium chloride, glyburide, TASK-1-IN-1 and 4-aminopyridine, asiaticoside did not produce significant effect on NE-induced vasoconstriction, and tetraethylammonium, Iberiotoxin and L-nitroarginine methyl ester all inhibited the relaxation effect of asiaticoside. In KCland NE-treated rings, asiaticoside obviously inhibited CaCl2-induced vascular contraction. CONCLUSION: Asiaticoside induces thoracic aorta relaxation by mediating high-conductance calcium-activated potassium channel opening, promoting nitric oxide release from endothelial cells and regulating Ca2+ influx and outflow, thereby reducing systolic blood pressure in rats.

Risk perception for fractures and its related factors among family caregivers of underage patients with osteogenesis imperfecta in China: A cross-sectional study.

PURPOSE: To describe the level of risk perception for fractures among family caregivers of children diagnosed with osteogenesis imperfecta, and explore the related factors. DESIGN AND METHODS: This was a cross-sectional survey study. A self-administered questionnaire on family caregivers' perception of fracture risk of underage patients with osteogenesis imperfecta was used. The study was performed in mainland China from May to December 2022, with 127 family caregivers of patients aged 3-17. Stepwise backwards multivariable linear regression analysis was undertaken to examine risk factors for caregivers' risk perception of fractures. RESULTS: A total of 16.54% of caregivers had a higher level of risk perception for fractures of patients. The caregiver's educational level, the family members, the patient's self-care ability, fracture times in the past year, and whether or not they had received community services were associated with the caregiver's risk perception for fracture. CONCLUSIONS: Patients with osteogenesis imperfecta will eventually leave the medical system and receive more support from themselves or family caregivers instead of health personnel. These findings should be incorporated into the prevention and health education of fractures in caregivers of underage patients with osteogenesis imperfecta to help develop effective risk communication strategies and induce caregivers to implement appropriate protective behaviors. PRACTICE IMPLICATIONS: It is important to evaluate the risk perception for fractures and its related factors among family caregivers of underage patients with osteogenesis imperfecta. Identifying these factors can help healthcare providers to screen caregivers with high perceived level of fracture risk in a quicker and earlier way. This study provides evidence for the establishment of interventions to balance caregivers' risk perception and patient socialization.

AlcoChange: A digital therapeutic for patients with alcohol-related liver disease.

Background & Aims: Maintenance of abstinence in alcohol-related liver disease (ARLD) is a major unmet therapeutic need. Digital therapeutics can deliver ongoing behavioural therapy, in real-time, for chronic conditions. The aim of this project was to develop and clinically test AlcoChange, a novel digital therapeutic for ARLD. Methods: AlcoChange was developed using validated behaviour change techniques and a digital alcohol breathalyser. This was an open-label, single-centre study. Patients with ARLD, ongoing alcohol use (within 1 month) and possession of a suitable smartphone were eligible. Patients were recruited from inpatient and outpatient settings, and received AlcoChange therapy for 3 months. The primary outcome was reduction in alcohol use from baseline to 3 months, measured by timeline follow-back. Secondary outcomes included: (i) compliance with the AlcoChange app, (ii) alcohol-related and all-cause hospital re-admissions up to 1 year, (iii) qualitative analysis to determine factors associated with compliance. Results: Sixty-five patients were recruited, of whom 41 completed the study per protocol. Patients compliant with the intervention (>60 logins over 3 months) had a significant reduction in alcohol use from baseline compared to non-compliant patients (median [IQR]: -100% [100% to -55.1%] vs. -57.1% [-95.3% to +32.13%], p = 0.029). The proportion attaining abstinence at 3 months was higher in the compliant group (57.1% vs. 22.2%, p = 0.025). The compliant group had a significantly decreased risk of subsequent alcohol-related re-admission up to 12 months (p = 0.008). Qualitative analysis demonstrated that receiving in-app feedback and the presence of a health-related 'sentinel event' were predictors of compliance with the intervention. Conclusions: Use of the novel digital therapeutic, AlcoChange, was associated with a significant reduction in alcohol use and an increase in the proportion of patients with ARLD attaining abstinence. Definitive randomised trials are warranted for this intervention. Impact and implications: Alcohol-related liver disease (ARLD) is an increasing health problem worldwide. The main cause of death and disability in ARLD is ongoing alcohol consumption, but few patients receive medications or talking therapy to maintain abstinence. This study demonstrated that a digital therapeutic, linked to a smartphone, may help reduce alcohol consumption and alcohol-related hospital admissions in these patients. If validated in larger, randomised, trials, digital therapeutics may have a role in the primary and secondary prevention of complicatons from ARLD.

[HVPG minimally invasive era: exploration based on forearm venous approach].

Objective: The transjugular or transfemoral approach is used as a common method for hepatic venous pressure gradient (HVPG) measurement in current practice. This study aims to confirm the safety and effectiveness of measuring HVPG via the forearm venous approach. Methods: Prospective recruitment was conducted for patients with cirrhosis who underwent HVPG measurement via the forearm venous approach at six hospitals in China and Japan from September 2020 to December 2020. Patients' clinical baseline information and HVPG measurement data were collected. The right median cubital vein or basilic vein approach for all enrolled patients was selected. The HVPG standard process was used to measure pressure. Research data were analyzed using SPSS 22.0 statistical software. Quantitative data were used to represent medians (interquartile ranges), while qualitative data were used to represent frequency and rates. The correlation between two sets of data was analyzed using Pearson correlation analysis. Results: A total of 43 cases were enrolled in this study. Of these, 41 (95.3%) successfully underwent HVPG measurement via the forearm venous approach. None of the patients had any serious complications. The median operation time for HVPG detection via forearm vein was 18.0 minutes (12.3~38.8 minutes). This study confirmed that HVPG was positively closely related to Child-Pugh score (r = 0.47, P = 0.002), albumin-bilirubin score (r = 0.37, P = 0.001), Lok index (r = 0.36, P = 0.02), liver stiffness (r = 0.58, P = 0.01), and spleen stiffness (r = 0.77, P = 0.01), while negatively correlated with albumin (r = -0.42, P = 0.006). Conclusion: The results of this multi-centre retrospective study suggest that HVPG measurement via the forearm venous approach is safe and feasible.

[Association between congenital hypothyroidism and in-hospital adverse outcomes in very low birth weight infants].

Objective: To investigate the association between congenital hypothyroidism (CH) and the adverse outcomes during hospitalization in very low birth weight infants (VLBWI). Methods: This prospective, multicenter observational cohort study was conducted based on the data from the Sino-northern Neonatal Network (SNN). Data of 5 818 VLBWI with birth weight <1 500 g and gestational age between 24-<37 weeks that were admitted to the 37 neonatal intensive care units from January 1st, 2019 to December 31st, 2022 were collected and analyzed. Thyroid function was first screened at 7 to 10 days after birth, followed by weekly tests within the first 4 weeks, and retested at 36 weeks of corrected gestational age or before discharge. The VLBWI were assigned to the CH group or non-CH group. Chi-square test, Fisher exact probability method, Wilcoxon rank sum test, univariate and multivariate Logistic regression were used to analyze the relationship between CH and poor prognosis during hospitalization in VLBWI. Results: A total of 5 818 eligible VLBWI were enrolled, with 2 982 (51.3%) males and the gestational age of 30 (29, 31) weeks. The incidence of CH was 5.5% (319 VLBWI). Among the CH group, only 121 VLBWI (37.9%) were diagnosed at the first screening. Univariate Logistic regression analysis showed that CH was associated with increased incidence of extrauterine growth retardation (EUGR) (OR=1.31(1.04-1.64), P<0.05) and retinopathy of prematurity (ROP) of stage Ⅲ and above (OR=1.74(1.11-2.75), P<0.05). However, multivariate Logistic regression analysis showed no significant correlation between CH and EUGR, moderate to severe bronchopulmonary dysplasia, grade Ⅲ to Ⅳ intraventricular hemorrhage, neonatal necrotizing enterocolitis in stage Ⅱ or above, and ROP in stage Ⅲ or above (OR=1.04 (0.81-1.33), 0.79 (0.54-1.15), 1.15 (0.58-2.26), 1.43 (0.81-2.53), 1.12 (0.70-1.80), all P>0.05). Conclusion: There is no significant correlation between CH and in-hospital adverse outcomes, possibly due to timely diagnosis and active replacement therapy.

An E-band multi-channel Doppler backscattering system on EAST.

An E-band (60-90 GHz) multi-channel Doppler backscattering (DBS) system with X-mode polarization has been installed on the Experimental Advanced Superconducting Tokamak (EAST), which can measure the turbulence at five different radial locations simultaneously. This system can launch 31 fixed microwave frequencies in the range of 60-90 GHz with a 1 GHz interval into the plasma, and five probing signals are selected by employing a reference signal and multiple filters. During experiments, the frequency of the reference signal is tunable in the E-band, and the selected probing signals can be changed as needed without any other adjustments, which can be performed in one shot or between shots. Furthermore, the incident angle can be adjusted from -10° to 20°, and the wavenumber range is 4-25 cm-1 with a wavenumber resolution of Δk/k ≤ 0.35. Ray tracing simulations are employed to calculate the scattering locations and the perpendicular wavenumber. In this article, the hardware design, ray tracing, and initial results obtained from the EAST plasma will be presented.

[Surveys on diagnosis and treatment of esophagogastric junction adenocarcinoma by the Chinese Laparoscopic Gastrointestinal Surgery Study Group-10 Research Team].

Objective: To investigate the diagnosis and treatment of esophagogastric junction (AEG) adenocarcinoma by members of the Chinese Laparoscopic Gastrointestinal Surgery Study Group (CLASS)-10 research team. Methods: A questionnaire was distributed to the CLASS-10 study group, which consists of investigators and research assistants from 32 centers in China, all of whom are gastric surgeons. The questionnaire was administered before the start of the study (2020) and mid-study (2022). The survey was developed to address the participants'perceptions of surgical consultation and management of AEG and included three main areas: diagnosis, surgical treatment, and perioperative management. In the second survey, the first two sections of the initial questionnaire were supplemented: the diagnosis section with a survey on the respondent's title, type of hospital, and definition of AEG, and the surgical treatment section with a survey on the perception of inferior mediastinal lymph node dissection as addressed in the CLASS-10 study. Respondents' clinical perceptions of AEG were recorded and the differences in perceptions between the two surveys analyzed. Results: Thirty-two and 34 questionnaires were returned in the first and second surveys, respectively. Regarding the definition of AEG adenocarcinoma, the highest acceptance rate was for the Chinese expert consensus (18/34, 52.9%), in which they are defined as lesions whose epicenter is located within 5 cm proximal or distal to the esophagogastric junction (EGJ) and crossing or touching the EGJ. Regarding the anatomic landmark for the EGJ, the percentage of respondents choosing the dentate line increased from 68.8% (22/32) to 88.2% (30/34) (P=0.143) between the two surveys. As to assessment of the longitudinal diameter and epicenter, the percentage of respondents choosing gastroscopy increased from 53.1% (17/32) to 73.5% (25/34) (P=0.040). Regarding the landmark for EGJ in surgical specimens, the percentage of respondents choosing the dentate line increased from 59.4% (19/32) to 85.3% (29/34) (P=0.027). In 2022, 82.4% (28/34) respondents reported that they were "skilled" in inferior mediastinal lymph node dissection for AEG. As to a safe proximal margin, the percentage of respondents choosing "≥1 cm, <2 cm" increased from 6.3% (2/32) to 26.5% (9/34) (P=0.158). Regarding the means of determining a safe proximal margin when the tumor is not infiltrating the serosa, the percentage of respondents choosing "intraoperative palpation" increased from 3.1% (1/32) to 23.5% (8/34), whereas those choosing "intraoperative gastroscopy" decreased from 62.5% (20/32) to 35.3% (12/32) (P=0.018). Conclusions: In the CLASS10 research team, the most commonly adopted definition of AEG was the Chinese expert consensus definition. We identified an increasing trend for choosing "endoscopy" and the "dentate line" when diagnosing AEG. Further, the definition of a safe proximal margin had decreased.

Addressing the Current Knowledge and Gaps in Research Surrounding Lysergic Acid Diethylamide (LSD), Psilocybin, and Psilocin in Rodent Models.

Lysergic acid Diethylamide (LSD), psilocybin, and psilocin are being intensively evaluated as potential therapeutics to treat depression, anxiety, substance use disorder, and a host of other psychiatric illnesses. Pre-clinical investigation of these compounds in rodent models forms a key component of their drug development process. In this review, we will summarize the evidence gathered to date surrounding LSD, psilocybin, and psilocin in rodent models of the psychedelic experience, behavioural organization, substance use, alcohol consumption, drug discrimination, anxiety, depression-like behaviour, stress response, and pharmacokinetics. In reviewing these topics, we identify three knowledge gaps as areas of future inquiry: sex differences, oral dosing rather than injection, and chronic dosing regimens. A comprehensive understanding of LSD, psilocybin, and psilocin's in vivo pharmacology may not only lead to their successful clinical implementation but optimize the use of these compounds as controls or references in the development of novel psychedelic therapeutics.

The role of shear viscosity as a biomarker for improving chronic kidney disease detection using shear wave elastography: A computational study using a validated finite element model.

The application of ultrasound shear wave elastography for detecting chronic kidney disease, namely renal fibrosis, has been widely studied. A good correlation between tissue Young's modulus and the degree of renal impairment has been established. However, the current limitation of this imaging modality pertains to the linear elastic assumption used in quantifying the stiffness of renal tissue in commercial shear wave elastography systems. As such, when underlying medical conditions such as acquired cystic kidney disease, which may potentially influence the viscous component of renal tissue, is present concurrently with renal fibrosis, the accuracy of the imaging modality in detecting chronic kidney disease may be affected. The findings in this study demonstrate that quantifying the stiffness of linear viscoelastic tissue using an approach similar to those implemented in commercial shear wave elastography systems led to percentage errors as high as 87%. The findings presented indicate that use of shear viscosity to detect changes in renal impairment led to a reduction in percentage error to values as low as 0.3%. For cases in which renal tissue was affected by multiple medical conditions, shear viscosity was found to be a good indicator in gauging the reliability of the Young's modulus (quantified through a shear wave dispersion analysis) in detecting chronic kidney disease. The findings show that percentage error in stiffness quantification can be reduced to as low as 0.6%. The present study demonstrates the potential use of renal shear viscosity as a biomarker to improve the detection of chronic kidney disease.

[Effects of laparoscopic hyperthermic intraperitoneal perfusion chemotherapy combined with intraperitoneal and systemic chemotherapy treatment in patients with untreated gastric cancer with peritoneal metastasis].

Objective: To investigate the efficacy of laparoscopic hyperthermic intraperitoneal perfusion chemotherapy combined with intraperitoneal and systemic chemotherapy (HIPEC-IP-IV) in the treatment of peritoneal metastases from gastric cancer (GCPM). Methods: This was a descriptive case series study. Indications for HIPEC-IP-IV treatment include: (1) pathologically confirmed gastric or esophagogastric junction adenocarcinoma; (2) age 20-85 years; (3) peritoneal metastases as the sole form of Stage IV disease, confirmed by computed tomography, laparoscopic exploration, ascites or peritoneal lavage fluid cytology; and (4) Eastern Cooperative Oncology Group performance status 0-1. Contraindications include: (1) routine blood tests, liver and renal function, and electrocardiogram showing no contraindications to chemotherapy; (2) no serious cardiopulmonary dysfunction; and (3) no intestinal obstruction or peritoneal adhesions. According to the above criteria, data of patients with GCPM who had undergone laparoscopic exploration and HIPEC from June 2015 to March 2021 in the Peking University Cancer Hospital Gastrointestinal Center were analyzed, after excluding those who had received antitumor medical or surgical treatment. Two weeks after laparoscopic exploration and HIPEC, the patients received intraperitoneal and systemic chemotherapy. They were evaluated every two to four cycles. Surgery was considered if the treatment was effective, as shown by achieving stable disease or a partial or complete response and negative cytology. The primary outcomes were surgical conversion rate, R0 resection rate, and overall survival. Results: Sixty-nine previously untreated patients with GCPM had undergone HIPEC-IP-IV, including 43 men and 26 women; with a median age of 59 (24-83) years. The median PCI was 10 (1-39). Thirteen patients (18.8%) underwent surgery after HIPEC-IP-IV, R0 being achieved in nine of them (13.0%). The median overall survival (OS) was 16.1 months. The median OS of patients with massive or moderate ascites and little or no ascites were 6.6 and 17.9 months, respectively (P<0.001). The median OS of patients who had undergone R0 surgery, non-R0 surgery, and no surgery were 32.8, 8.0, and 14.9 months, respectively (P=0.007). Conclusions: HIPEC-IP-IV is a feasible treatment protocol for GCPM. Patients with massive or moderate ascites have a poor prognosis. Candidates for surgery should be selected carefully from those in whom treatment has been effective and R0 should be aimed for.

[CT perfusion combined with energy spectrum imaging to evaluate the short-term efficacy of bronchial arterial chemoembolization for lung cancer].

Objective: To evaluate the clinical value of dynamic volumetric CT perfusion combined with energy spectrum imaging in bronchial arterial chemoembolization (BACE) in patients with lung cancer. Methods: The data of 31 patients with lung cancer confirmed by pathology and treated with BACE in Lishui Central Hospital from January 2018 to February 2022 were retrospectively collected, including 23 men and 8 women, aged 31-84 (67) years. All patients received perfusion scans of lesion sites within 1 week before surgery and 1 month after surgery. We collected and compared the changes in preoperative and postoperative perfusion parameters such as blood flow (BF), blood volume (BV), mean through time (MTT), permeability surface (PS) and energy spectrum parameters including arterial phase CT value (CTA), venous phase CT value (CTV), arterial phase iodine concentration (ICA), venous phase of iodine concentration (ICV), arterial standardization iodine concentration (NICA), and intravenous standardized iodine concentration (NICV) to confirm the significance of these parameters in evaluating the short-term efficacy of BACE in the treatment of advanced lung cancer. Data normality was tested using the Kolmogorov-Smirnov test and normally distributed measurement data are expressed here as mean ± standard deviation; the independent-samples t-test was used for comparisons between two groups. The measurement data that were not normally distributed are expressed as median (interquartile interval) [M (Q1, Q3)], and the comparison between the two groups used the Kruskal-Wallis test. Count data are expressed as cases (%), and comparisons between groups used the χ2 test. Results: The objective response rate (ORR) and disease control rate (DCR) at 1 month after BACE were 54.8% (17/31) and 96.8% (30/31), respectively. CT perfusion parameters and energy spectrum parameters of patients before and after BACE treatment were compared. The results showed that BF, BV, MTT, ICA, ICV and NICV were significantly decreased after BACE treatment compared with before treatment, and the differences were statistically significant[58.06 (40.47,87.22) vs.23.57(10.92, 36.24) ml·min-1·100g-1,3.33(2.86,6.09) vs.2.12(1.96,3.61)ml/100g,2.70(2.19,3.88) vs.1.53 (1.12,2.25)s, 3.51 (3.11,4.14)vs.1.74 (1.26,2.50)mg/ml,2.00 (1.30,2.45) vs.1.32(0.92,1.76)mg/ml,0.51(0.42,0.57) vs.0.33(0.23,0.39)](all P<0.05). At the same time, compared with the non-remission group, the study results showed that the difference of parameters in remission group before and after BACE was more obvious, including ΔBF, ΔBV, ΔMTT, ΔPS, ΔCTA, ΔCTV, ΔICA, ΔICV, ΔNICA, ΔNICV were significantly increased, and the difference was statistically significant [36.82(32.38, 45.34) vs.9.50(-1.43, 12.34) ml·min-1·100g-1,4.46(2.52, 5.79) vs.0.22(-0.76, 4.09) ml/100g,4.22(2.25, 6.77) vs.0.43(-2.53, 1.88) s,10.07 (2.89, 13.13) vs.-2.01(-6.77, 4.28) ml·min-1·100g-1,14.22(11.88, 20.57) vs.4.18(-5.25, 6.37) HU, 34.6(14.88, 43.15) vs.11.60(0.26, 25.05) HU,0.95(0.54, 1.47) vs.0.11(0.20, 0.59) mg/ml,1.57(1.10, 2.38) vs. 0.26(-0.21, 0.63) mg/ml,0.05(0.03, 0.08) vs.-0.02(-0.04, 0.01),0.18(0.13, 0.21)vs. 0.11(-0.06, 0.16)](all P<0.05). Conclusions: CT perfusion combined with spectral imaging could effectively evaluate the changes in tumor vascular perfusion in patients with advanced lung cancer before and after BACE treatment, which has important value in judging the short-term efficacy after treatment.

Dual Cannabinoid and Orexin Regulation of Anhedonic Behaviour Caused by Prolonged Restraint Stress.

The endocannabinoid and orexin systems share many biological functions, including wakefulness, stress response, reward processing, and mood. While these systems work against one another with respect to arousal, chronic stress-induced downregulation of both systems often leads to anhedonia or the inability to experience pleasure from natural rewards. In the current study, a 24 h restraint stress test (24 h RST) reduced sucrose preference in adult male and female C57BL/6 mice. Prior to the stressor, subsets of mice were intraperitoneally administered cannabinoid and orexin receptor agonists, antagonists, and combinations of these drugs. Restraint mice that received the cannabinoid receptor type 1 (CB1R) antagonist SR141716A, orexin receptor type 2 (OX2R) agonist YNT-185, and the combination of SR141716A and YNT-185, exhibited less anhedonia compared to vehicle/control mice. Thus, the 24 h RST likely decreased orexin signaling, which was then restored by YNT-185. Receptor colocalization analysis throughout mesocorticolimbic brain regions revealed increased CB1R-OX1R colocalization from SR141716A and YNT-185 treatments. Although a previous study from our group showed additive cataleptic effects between CP55,940 and the dual orexin receptor antagonist (TCS-1102), the opposite combination of pharmacological agents proved additive for sucrose preference. Taken together, these results reveal more of the complex interactions between the endocannabinoid and orexin systems.

[Establishment and data quality control of a multicenter prospective database for prevalence of abdominal complications after gastroenterological surgery].

As the main cause of secondary operation and postoperative death, the incidence of intraperitoneal infectious complications varies significantly in different medical centers in China. Due to the lack of national data, it is not possible to assess and develop appropriate diagnosis and treatment strategies properly. To provide a high-quality data platform for complication registration and clinical research, a multicenter prospective database for the Prevalence of Abdominal Complications After GastroEnterological surgery was established. Based on the Hospital Information System (HIS)of 20 medical centers in China, the electronic case reporting form (e-CRF) listed on the website was used to collect medical information of patients undergoing gastric or colorectal cancer surgery. The data were verified by on-site auditing, and data cleaning was performed by R software. After the data cleaning, the data in the database was checked and evaluated by the principle investigators and data administrators. When all data queries and questions were corrected and answered, the database was locked to establish a multicenter prospective database for postoperative abdominal infectious complications (the PACAGE database). The PACAGE database has rich information resources and high data quality and is a good data platform for complication registration and clinical research.

[Comparison of safety of total laparoscopic versus laparoscopic-assisted radical gastrectomy for distal gastric cancer in older patients].

Objective: To compare the effectiveness of total laparoscopic versus laparoscopic-assisted distal gastrectomy and investigate the safety and replicability of total laparoscopic distal gastrectomy in older patients. Methods: This was a retrospective cohort study. The inclusion criteria were as follows: (1) age ≥65 years; (2) malignant gastric tumor diagnosed pathologically preoperatively; (3) Eastern Cooperative Oncology Group performance status score 0-1; (4) Grade I-III American Society of Anesthesiologists physical status; (5) preoperative clinical tumor stage I-III; (6) total laparoscopic or laparoscopic-assisted distal gastrectomy performed; and (7) gastrointestinal tract reconstruction using uncut Roux-en-Y or Billroth-II+Braun procedure. Patients who had received neoadjuvant therapy, undergone conversion to open surgery, or had serious comorbidities or incomplete data were excluded. The clinical data of 129 patients who met the above criteria and had undergone laparoscopic surgery for gastric cancer from January 2012 to December 2021 in the Gastrointestinal Cancer Center in the Beijing Cancer Hospital were analyzed. According to the operation method, the patients were divided into total laparoscopic group and laparoscopic-assisted group. Variables studied comprised: (1) surgical procedure and postoperative recovery; (2) postoperative pathological findings; and (3) postoperative complications. Measurement data with skewed distribution are represented as mean(quartile 1, quartile 3). Comparisons between groups were evaluated using the Mann-Whitney U test. Results: After propensity score matching in a 1:1 ratio, there were 40 patients in the total laparoscopic distal gastrectomy group and 40 in the laparoscopic-assisted distal gastrectomy group. Baseline characteristics did not differ significantly between the two groups (all P>0.05).Compared with the laparoscopic-assisted group, the total laparoscopic group had shorter main incisions (4.1±1.0 cm vs. 8.5±2.8 cm, t=9.375, P<0.001), time to fluid intake [4.0 (3.0, 4.8) days vs. 5.0 (4.0, 6.0) days, Z=2.167, P=0.030], and duration of indwelling abdominal drainage catheter [6.0 (6.0, 7.0) days vs. 7.0 (6.0, 8.0) days, Z=2.323, P=0.020]. Numerical Rating Scale scores on postoperative days 1 and 2 were higher in the total laparoscopic than the laparoscopic-assisted group [2.5 (1.0, 3.0) vs. 1.5 (1.0, 2.0), Z=1.980, P=0.048; 2.0 (1.0, 3.0) vs. 1.0 (1.0, 2.0), Z=2.334, P=0.020, respectively]. However, there were no significant differences between the groups in operation time, intraoperative blood loss, white blood cell count, hemoglobin concentration, or albumin concentration on postoperative day 1, time to ambulation, mean time to bowel movement, postoperative admission to the intensive care unit, length of postoperative hospital stay, or Numerical Rating Scale scores on postoperative day 3 (all P>0.05). There were also no significant differences between the two groups in maximum tumor diameter, pathological tumor type, total number of lymph nodes dissected, or total number of positive lymph nodes (all P>0.05). The incidence of postoperative complications was 15.0% (6/40) in the total laparoscopic group and the laparoscopic-assisted group; these differences are not significant (χ2<0.001, P>0.999). Conclusions: Compared with laparoscopic-assisted radical gastrectomy for distal gastric cancer, total laparoscopic surgery has the advantages of shorter incision, shorter time to fluid intake, and shorter duration of indwelling abdominal drainage catheter in older patients (age ≥65 years). Total laparoscopic radical gastrectomy for distal gastric cancer does not increase the risk of postoperative complications and could therefore be performed more frequently.

[Interaction of polycyclic aromatic hydrocarbon DNA adducts and telomere length on missed abortion].

Objective: To analyze the contribution and interaction of polycyclic aromatic hydrocarbons (PAH)-DNA adducts and changes of telomere length (TL) on missed abortion. Methods: From March to December 2019, patients with missed abortion in the First Hospital of Shanxi Medical University and pregnant women with normal pregnancy but voluntary abortion in the same department during the same period were selected and divided into a case group and a control group. Questionnaire was used to investigate the general situation and the pregnancy situation of the subjects. The abortion villi were collected and the content of PAH-DNA adducts and TL was detected. Logistic regression model was used to analyze the associated factors of missed abortion. R epiR package and Mediation package were used to analyze the effect and relationship between PAH-DNA adducts and TL on missed abortion. Results: The age of the subjects was(29.92±5.69)years old. The M(Q1,Q3)of PAH-DNA adducts was 453.75(404.61, 504.72) pg/ml. The M(Q1,Q3)of TL was 1.21(0.77, 1.72). The content of PAH-DNA adducts in the case group was higher than that in the control group (Z=-2.10, P=0.036), while the TL was lower than that in the control group (Z=-4.05, P<0.001). Multivariate logistic regression showed that low, medium and high levels of PAH-DNA adducts (OR=3.17,95%CI:1.41-7.14;OR=2.85,95%CI:1.25-6.52;OR=2.46,95%CI:1.07-5.64), and long, medium and short levels of TL (OR=2.50,95%CI:1.11-5.63;OR=3.32,95%CI:1.45-7.56;OR=3.22,95%CI:1.42-7.26) were all risk factors for missed abortion. The medium level of PAH-DNA adducts had a 2.76-fold higher risk of shortened TL than those with the lowest level, and no mediating role of TL was found. The stratified analysis showed that when the TL level was longer (>1.21), the low and high levels of PAH-DNA adducts were associated with missed abortion (all P<0.05); when the TL level was shorter (<1.21), the medium level of PAH-DNA adducts was associated with abortion (P=0.025). At lower levels of PAH-DNA adducts, no effect of TL on missed abortion was observed, while, at higher levels, TL was strongly associated with missed abortion (OR=7.50,95%CI:1.95-28.82;OR=6.04,95%CI:1.54-23.65;OR=9.05,95%CI:2.34-35.04). The interaction analysis found that the AP was 0.72 (95%CI: 0.46-0.99), and the SI was 5.21 (95%CI: 2.30-11.77). Conclusion: The high level of PAH-DNA adducts and shortened TL may increase the risk of missed abortion, and there may be a positive additive interaction between the two factors on missed abortion.

A computational framework for the multiphysics simulation of microbubble-mediated sonothrombolysis using a forward-viewing intravascular transducer.

Sonothrombolysis is a technique that utilises ultrasound waves to excite microbubbles surrounding a clot. Clot lysis is achieved through mechanical damage induced by acoustic cavitation and through local clot displacement induced by acoustic radiation force (ARF). Despite the potential of microbubble-mediated sonothrombolysis, the selection of the optimal ultrasound and microbubble parameters remains a challenge. Existing experimental studies are not able to provide a complete picture of how ultrasound and microbubble characteristics influence the outcome of sonothrombolysis. Likewise, computational studies have not been applied in detail in the context of sonothrombolysis. Hence, the effect of interaction between the bubble dynamics and acoustic propagation on the acoustic streaming and clot deformation remains unclear. In the present study, we report for the first time the computational framework that couples the bubble dynamic phenomena with the acoustic propagation in a bubbly medium to simulate microbubble-mediated sonothrombolysis using a forward-viewing transducer. The computational framework was used to investigate the effects of ultrasound properties (pressure and frequency) and microbubble characteristics (radius and concentration) on the outcome of sonothrombolysis. Four major findings were obtained from the simulation results: (i) ultrasound pressure plays the most dominant role over all the other parameters in affecting the bubble dynamics, acoustic attenuation, ARF, acoustic streaming, and clot displacement, (ii) smaller microbubbles could contribute to a more violent oscillation and improve the ARF simultaneously when they are stimulated at higher ultrasound pressure, (iii) higher microbubbles concentration increases the ARF, and (iv) the effect of ultrasound frequency on acoustic attenuation is dependent on the ultrasound pressure. These results may provide fundamental insight that is crucial in bringing sonothrombolysis closer to clinical implementation.

[Building world leading surgical oncology for gastric cancer in China].

This century has seen significant advances in the treatment and research of gastric cancer in China. Chinese scholars have made a series of key technological breakthroughs in minimally invasive surgery, perioperative treatment and artificial intelligence diagnosis. These world-leading clinical researches have improved treatment outcomes and reduced surgical trauma. Global surveillance of trends in cancer survival 2000-14 reported that survival of gastric cancer in China has significantly improved during the last 20 years. This paper reviews the research history of surgical oncology for gastric cancer in China, summarises the experience and attempts to explore the future direction.

Molecular and cellular mechanisms underlying brain region-specific endocannabinoid system modulation by estradiol across the rodent estrus cycle.

Neurological crosstalk between the endocannabinoid and estrogen systems has been a growing topic of discussion over the last decade. Although the main estrogenic ligand, estradiol (E2), influences endocannabinoid signaling in both male and female animals, the latter experiences significant and rhythmic fluctuations in E2 as well as other sex hormones. This is referred to as the menstrual cycle in women and the estrus cycle in rodents such as mice and rats. Consisting of 4 distinct hormone-driven phases, the rodent estrus cycle modulates both endocannabinoid and exogenous cannabinoid signaling resulting in unique behavioral outcomes based on the cycle phase. For example, cannabinoid receptor agonist-induced antinociception is greatest during proestrus and estrus, when circulating and brain levels of E2 are high, as compared to metestrus and diestrus when E2 concentrations are low. Pain processing occurs throughout the cerebral cortex and amygdala of the forebrain; periaqueductal grey of the midbrain; and medulla and spine of the hindbrain. As a result, past molecular investigations on these endocannabinoid-estrogen system interactions have focused on these specific brain regions. Here, we will bridge regional molecular trends with neurophysiological evidence of how plasma membrane estrogen receptor (ER) activation by E2 leads to postsynaptic endocannabinoid synthesis, retrograde signaling, and alterations in inhibitory neurotransmission. These signaling pathways depend on ER heterodimers, current knowledge of which will also be detailed in this review. Overall, the aim of this review article is to systematically summarize how the cannabinoid receptors and endocannabinoids change in expression and function in specific brain regions throughout the estrus cycle.

Estradiol-dependent hypocretinergic/orexinergic behaviors throughout the estrous cycle.

RATIONALE: The female menstrual or estrous cycle and its associated fluctuations in circulating estradiol (E2), progesterone, and other gonadal hormones alter orexin or hypocretin peptide production and receptor activity. Depending on the estrous cycle phase, the transcription of prepro-orexin mRNA, post-translational modification of orexin peptide, and abundance of orexin receptors change in a brain region-specific manner. The most dramatic changes occur in the hypothalamus, which is considered the starting point of the hypothalamic-pituitary-gonadal axis as well as the hub of orexin-producing neurons. Thus, hypothalamus-regulated behaviors, including arousal, feeding, reward processing, and the stress response depend on coordinated efforts between E2, progesterone, and the orexin system. Given the rise of orexin therapeutics for various neuropsychiatric conditions including insomnia and affective disorders, it is important to delineate the behavioral outcomes of this drug class in both sexes, as well as within different time points of the female reproductive cycle. OBJECTIVES: Summarize how the menstrual or estrous cycle affects orexin system functionality in animal models in order to predict how orexin pharmacotherapies exert varying degrees of behavioral effects across the dynamic hormonal milieu.