Preoperative serum cortisone levels are associated with cognition in preschool-aged children with tetralogy of Fallot after corrective surgery: new evidence from human populations and mice.

BACKGROUND: Tetralogy of Fallot (TOF) is the most common cyanotic congenital heart disease. Children with TOF would be confronted with neurological impairment across their lifetime. Our study aimed to identify the risk factors for cerebral morphology changes and cognition in postoperative preschool-aged children with TOF. METHODS: We used mass spectrometry (MS) technology to assess the levels of serum metabolites, Wechsler preschool and primary scale of intelligence-Fourth edition (WPPSI-IV) index scores to evaluate neurodevelopmental levels and multimodal magnetic resonance imaging (MRI) to detect cortical morphological changes. RESULTS: Multiple linear regression showed that preoperative levels of serum cortisone were positively correlated with the gyrification index of the left inferior parietal gyrus in children with TOF and negatively related to their lower visual spaces index and nonverbal index. Meanwhile, preoperative SpO2 was negatively correlated with levels of serum cortisone after adjusting for all covariates. Furthermore, after intervening levels of cortisone in chronic hypoxic model mice, total brain volumes were reduced at both postnatal (P) 11.5 and P30 days. CONCLUSIONS: Our results suggest that preoperative serum cortisone levels could be used as a biomarker of neurodevelopmental impairment in children with TOF. Our study findings emphasized that preoperative levels of cortisone could influence cerebral development and cognition abilities in children with TOF.

Autophagy of OTUD5 destabilizes GPX4 to confer ferroptosis-dependent kidney injury.

Ferroptosis is an iron-dependent programmed cell death associated with severe kidney diseases, linked to decreased glutathione peroxidase 4 (GPX4). However, the spatial distribution of renal GPX4-mediated ferroptosis and the molecular events causing GPX4 reduction during ischemia-reperfusion (I/R) remain largely unknown. Using spatial transcriptomics, we identify that GPX4 is situated at the interface of the inner cortex and outer medulla, a hyperactive ferroptosis site post-I/R injury. We further discover OTU deubiquitinase 5 (OTUD5) as a GPX4-binding protein that confers ferroptosis resistance by stabilizing GPX4. During I/R, ferroptosis is induced by mTORC1-mediated autophagy, causing OTUD5 degradation and subsequent GPX4 decay. Functionally, OTUD5 deletion intensifies renal tubular cell ferroptosis and exacerbates acute kidney injury, while AAV-mediated OTUD5 delivery mitigates ferroptosis and promotes renal function recovery from I/R injury. Overall, this study highlights a new autophagy-dependent ferroptosis module: hypoxia/ischemia-induced OTUD5 autophagy triggers GPX4 degradation, offering a potential therapeutic avenue for I/R-related kidney diseases.

Banxia Xiexin Decoction Alleviated Cerebral Glucose Metabolism Disorder by Regulating Intestinal Microbiota in APP/PS1 Mice.

OBJECTIVE: To identify whether Banxia Xiexin Decoction (BXD) alleviates cerebral glucose metabolism disorder by intestinal microbiota regulation in APP/PS1 mice. METHODS: Forty-five 3-month-old male APP/PS1 mice were divided into 3 groups using a random number table (n=15 per group), including a model group (MG), a liraglutide group (LG) and a BXD group (BG). Fifteen 3-month-old male C57BL/6J wild-type mice were used as the control group (CG). Mice in the BG were administered BXD granules by gavage at a dose of 6 g/(kg•d) for 3 months, while mice in the LG were injected intraperitoneally once daily with Liraglutide Injection (25 nmol/kg) for 3 months. Firstly, liquid chromatography with tandem-mass spectrometry was used to analyze the active components of BXD granules and the medicated serum of BXD. Then, the cognitive deficits, Aß pathological change and synaptic plasticity markers, including synaptophysin (SYP) and postsynaptic density protein 95 (PSD95), were measured in APP/PS1 mice. Brain glucose uptake was detected by micropositron emission tomography. Intestinal microbial constituents were detected by 16S rRNA sequencing. The levels of intestinal glucagon-like peptide 1 (GLP-1) and cerebral GLP-1 receptor (GLP-1R), as well as the phosphoinositide-3-kinase/protein kinase B/glycogen synthase kinase-3ß (PI3K/Akt/GSK3ß) insulin signaling pathway were determined by immunohistochemical (IHC) staining and Western blot analysis, respectively. RESULTS: BXD ameliorated cognitive deficits and Aß pathological features (P<0.01). The expressions of SYP and PSD95 in the BG were higher than those in the MG (P<0.01). Brain glucose uptake in the BG was higher than that in the MG (P<0.01). The intestinal microbial composition in the BG was partially reversed. The levels of intestinal GLP-1 in the BG were higher than those in the MG (P<0.01). Compared with the MG, the expression levels of hippocampal GLP-1R, Akt, PI3K and p-PI3K in the BG were significantly increased (P<0.01), while the levels of GSK3ß were reduced (P<0.01). CONCLUSION: BXD exhibited protective effects against Alzheimer's disease by regulating the gut microbiota/GLP-1/GLP-1R, enhancing PI3K/Akt/GSK3ß insulin signaling pathway, and improving brain glucose metabolism.

Physiological and biochemical mechanisms of brassinosteroid in improving anti-cadmium stress ability of Panax notoginseng / 中国中药杂志

In this study, the effect of brassinosteroid(BR) on the physiological and biochemical conditions of 2-year-old Panax notoginseng under the cadmium stress was investigated by the pot experiments. The results showed that cadmium treatment at 10 mg·kg~(-1) inhibited the root viability of P. notoginseng, significantly increased the content of H_2O_2 and MDA in the leaves and roots of P. noto-ginseng, caused oxidative damage of P. notoginseng, and reduced the activities of SOD and CAT. Cadmium stress reduced the chlorophyll content of P. notoginseng, increased leaf F_o, reduced F_m, F_v/F_m, and PIABS, and damaged the photosynthesis system of P. notoginseng. Cadmium treatment increased the soluble sugar content of P. notoginseng leaves and roots, inhibited the synthesis of soluble proteins, reduced the fresh weight and dry weight, and inhibited the growth of P. notoginseng. External spray application of 0.1 mg·L~(-1) BR reduced the H_2O_2 and MDA content in P. notoginseng leaves and roots under the cadmium stress, alleviated cadmium-induced oxidative damage to P. notoginseng, improved the antioxidant enzyme activity and root activity of P. notoginseng, increased the content of chlorophyll, reduced the F_o of P. notoginseng leaves, increased F_m, F_v/F_m, and PIABS, alleviated the cadmium-induced damage to the photosynthesis system, and improved the synthesis ability of soluble proteins. In summary, BR can enhance the anti-cadmium stress ability of P. notoginseng by regulating the antioxidant enzyme system and photosynthesis system of P. notoginseng under the cadmium stress. In the context of 0.1 mg·L~(-1) BR, P. notoginseng can better absorb and utilize light energy and synthesize more nutrients, which is more suitable for the growth and development of P. notoginseng.

Effects of propiconazole on physiological and biochemical properties of Panax notoginseng and dietary risk assessment / 中国中药杂志

To study the residue and dietary risk of propiconazole in Panax notoginseng and the effects on physiological and bioche-mical properties of P. notoginseng, we conducted foliar spraying of propiconazole on P. notoginseng in pot experiments. The physiolo-gical and biochemical properties studied included leaf damage, osmoregulatory substance content, antioxidant enzyme system, non-enzymatic system, and saponin content in the main root. The results showed that at the same application concentration, the residual amount of propiconazole in each part of P. notoginseng increased with the increase in the times of application and decreased with the extension of harvest interval. After one-time application of propiconazole according to the recommended dose(132 g·hm~(-2)) for P. ginseng, the half-life was 11.37-13.67 days. After 1-2 times of application in P. notoginseng, propiconazole had a low risk of dietary intake and safety threat to the population. The propiconazole treatment at the recommended concentration and above significantly increased the malondialdehyde(MDA) content, relative conductivity, and osmoregulatory substances and caused the accumulation of reactive oxygen species in P. notoginseng leaves. The propiconazole treatment at half(66 g·hm~(-2)) of the recommended dose for P. ginseng significantly increased the activities of superoxide dismutase(SOD), peroxidase(POD), and catalase(CAT) in P. notoginseng leaves. The propiconazole treatment at 132 g·hm~(-2) above inhibited the activities of glutathione reductase(GR) and glutathione S-transferase(GST), thereby reducing glutathione(GSH) content. Proconazole treatment changed the proportion of 5 main saponins in the main root of P. notoginseng. The treatment with 66 g·hm~(-2) propiconazole promoted the accumulation of saponins, while that with 132 g·hm~(-2) and above propiconazole significantly inhibited the accumulation of saponins. In summary, using propiconazole at 132 g·hm~(-2) to prevent and treat P. notoginseng diseases will cause stress on P. notoginseng, while propiconazole treatment at 66 g·hm~(-2) will not cause stress on P. notoginseng but promote the accumulation of saponins. The effect of propiconazole on P. notoginseng diseases remains to be studied.

The clinical effect of stereotactic radiation therapy combined with sorafenib in the treatment of primary hepatic cancer / 中国医师进修杂志

Objective:To investigate the clinical effect of stereotactic radiation therapy combined with sorafenib in the treatment of primary hepatic cancer (PHC).Methods:Ninety-two PHC patients admitted to Cancer Hospital of China Medical University from January 2017 to May 2018 were selected and divided into the observation group and the control group according to the random number table method, with 46 cases in each group. The control group was treated with stereotactic radiation therapy, and the observation group was treated with sorafenib on the basis of the control group. Clinical efficacy and incidence of adverse reactions in the two groups were compared; the scores of Karnofsky performance scale (KPS) and the levels of serum vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), hypoxia-inducing factor (HIF-1α), soluble interleukin-2 receptor (sIL-2R), transforming growth factor (TGF-β1) and alpha-fetoprotein (AFP) before and after the treatment between the two groups were compared. The overall survival (OS) of patients in both groups was recorded after 36 months of follow-up.Results:The total effective rate in the observation group was higher than that in the control group: 84.78%(39/46) vs. 65.22%(30/46), there was statistical difference ( χ2 = 4.70, P<0.05). After the treatment, the score of KPS in the observation group was higher than that in the control group: (85.06 ± 7.19) scores vs. (71.16 ± 7.08) scores; the levels of VEGF, bFGF, HIF-1α, AFP, TGF-β1, sIL-2R in the observation group were lower than those in the control group: (189.52 ± 31.47) ng/L vs. (235.81 ± 35.45) ng/L, (3.89 ± 0.97) ng/L vs. (6.74 ± 1.85) ng/L, (50.17 ± 6.09) ng/L vs. (53.07 ± 6.28) ng/L, (85.76 ± 14.09) μg/L vs. (131.51 ± 18.74) μg/L, (81.07 ± 12.96) μg/L vs. (106.58 ± 15.07) μg/L, (311.58 ± 74.81) kU/L vs. (405.97 ± 85.74) kU/L, there were statistical differences ( P<0.05). The results of 36 months follow-up showed that the 1-year and 3-year OS in the observation group were higher than those in the control group: 69.57% (32/46) vs. 58.70% (27/46), 43.47% (20/46) vs. 28.26 %(13/46), there were significant differences ( χ2 = 4.78, 3.94, P<0.05). Conclusions:Stereotactic radiation therapy combined with sorafenib can effectively improve the efficacy of PHC patients, reduce the expression of VEGF and bFGF, effectively inhibit tumor growth, but also prolong the survival time of patients, with both safety and high effectiveness, and good use value.

Perioperative management and operative treatment of malignant tumor of anal canal merging severe abdominal protuberance / 中华胃肠外科杂志

Objective: To report the perioperative management and robot-assisted minimally invasive surgery results of one case with malignant tumor of anal canal combined with severe abdominal distention. Methods: A 66-year-old male suffer from adenocarcinoma of anal canal (T3N0M0) with megacolon, megabladder and scoliosis. The extreme distention of the colon and bladder result in severe abdominal distention. The left diaphragm moved up markedly and the heart was moved to the right side of the thoracic cavity. Moreover, there was also anal stenosis with incomplete intestinal obstruction. Preoperative preparation: fluid diet, intravenous nutrition and repeated enema to void feces and gas in the large intestine 1 week before operation. Foley catheter was placed three days before surgery and irrigated with saline. After relief of abdominal distention, robotic-assisted abdominoperineal resection+ subtotal colectomy+colostomy was performed. Results: Water intake within 6 hours post-operatively; ambulance on Day 1; anal passage of gas on Day 2; semi-fluid diet on Day 3; safely discharged on Day 6. Conclusion: Robotic-assisted minimally invasive surgery is safe and feasible for patients with malignant tumor of anal canal combined with severe abdominal distention after appropriate and effective preoperative preparation to relieve abdominal distention.

SIRT1 activation synergizes with FXR agonism in hepatoprotection via governing nucleocytoplasmic shuttling and degradation of FXR

Farnesoid X receptor (FXR) is widely accepted as a promising target for various liver diseases; however, panels of ligands in drug development show limited clinical benefits, without a clear mechanism. Here, we reveal that acetylation initiates and orchestrates FXR nucleocytoplasmic shuttling and then enhances degradation by the cytosolic E3 ligase CHIP under conditions of liver injury, which represents the major culprit that limits the clinical benefits of FXR agonists against liver diseases. Upon inflammatory and apoptotic stimulation, enhanced FXR acetylation at K217, closed to the nuclear location signal, blocks its recognition by importin KPNA3, thereby preventing its nuclear import. Concomitantly, reduced phosphorylation at T442 within the nuclear export signals promotes its recognition by exportin CRM1, and thereby facilitating FXR export to the cytosol. Acetylation governs nucleocytoplasmic shuttling of FXR, resulting in enhanced cytosolic retention of FXR that is amenable to degradation by CHIP. SIRT1 activators reduce FXR acetylation and prevent its cytosolic degradation. More importantly, SIRT1 activators synergize with FXR agonists in combating acute and chronic liver injuries. In conclusion, these findings innovate a promising strategy to develop therapeutics against liver diseases by combining SIRT1 activators and FXR agonists.

Long Non-Coding RNA CRNDE Functions as a Tumor Promoter by Modulating the ERK/MAPK Signaling Pathway in Neuroblastoma Cells.

OBJECTIVE: The long non-coding RNA (lncRNA) colorectal neoplasia differentially expressed (CRNDE) is considered a carcinogenic promoter in various human malignancies. However, the role and underlying mechanism of action of CRNDE during carcinogenesis in neuroblastoma remain unknown. METHODS: CRNDE transcript levels were detected in neuroblastoma tissues and adjacent normal tissues. The effects of CRNDE overexpression and knockdown on the viability of SH-SY5Y and SK-N-AS cells were determined using the Cell Counting Kit-8 (CCK-8) assay. Flow cytometry was performed to measure the role of CRNDE in apoptosis and the cell cycle in neuroblastoma cells. Moreover, the transwell assay was used to evaluate the role of CRNDE in the migration and invasion of tumor cells. The levels of ERK/MAPK pathway-related proteins were evaluated using western blotting. The in vivo role of CRNDE in tumor growth and apoptosis was evaluated in a xenograft mouse model of human neuroblastoma. RESULTS: The relative expression of CRNDE was significantly higher in neuroblastoma tissues than in the adjacent normal tissues. Moreover, knockdown of CRNDE inhibited tumor cell proliferation and induced apoptosis and cell cycle arrest, whereas elevation of CRNDE promoted cell growth and inhibited apoptosis in neuroblastoma cells. In addition, depletion of CRNDE suppressed migration and invasion, whereas overexpression of CRNDE enhanced the migratory and invasive potential of SH-SY5Y and SK-N-AS cells. At the mechanistic level, western blotting showed that CRNDE exerted its oncogenic role by affecting the ERK/MAPK signaling pathway. Furthermore, animal experiments confirmed that CRNDE promotes tumor growth and inhibits apoptosis in neuroblastoma in vivo. CONCLUSION: The present study revealed that CRNDE plays a critical role in the proliferation, apoptosis, migration, and invasion of neuroblastoma by altering the ERK/MAPK signaling pathway, representing a novel molecular target for the treatment of neuroblastoma.

Leptin activates the JAK/STAT pathway to promote angiogenesis in RF/6A cells in vitro.

AIM: To investigate the effect of leptin on the angiogenesis of RF/6A cells (monkey retinal choroidal endothelial cells) in vitro and test the cellular signaling in the mechanism. METHODS: RF/6A cells were cultured in vitro and randomly divided into four groups: normal control, with leptin at 50, 100, 200 ng/mL for cell counting kit-8 (CCK8). RF/6A cell proliferation and migration were examined by Transwell assays, while RF/6A cell tube formation by Matrigel assay. JAK2, p-JAK2, STAT3, and p-STAT3 protein expression was measured by Western blotting. Cells were then divided into the following treatment groups: control, 100 ng/mL leptin and AG-490 (100 ng/mL leptin+10 µmol/L AG-490) for examinations of RF/6A cellular behaviour again. Analysis of differences was carried out using one-way ANOVA and least significant difference (LSD). RESULTS: RF/6A cell proliferation, migration and cell tube formation were promoted significantly by leptin in a dose-dependent manner (P<0.05). Western blotting showed that leptin up-regulated p-JAK2 and p-STAT3 expression levels. Treatment with the JAK/STAT pathway inhibitor, AG-490, decreased leptin-induced p-JAK2 and p-STAT3 expression, and inhibited cell proliferation, migration and cell tube formation induced by leptin (P<0.05). CONCLUSION: Leptin can promote RF/6A cell angiogenesis in vitro via activation of the JAK2/STAT3 signaling pathway.

Risk factors of short-prognosis after minimally invasive surgery in elderly patients with hypertensive basal ganglia intracerebral hemorrhage / 国际外科学杂志

Objective:To investigate the short-term prognosis of elderly patients with hypertensive basal ganglia intracerebral hemorrhage after minimally invasive surgery and to analyze the risk factors.Methods:The clinical data of 96 elderly patients with hypertensive basal ganglia intracerebral hemorrhage admitted to the Department of Neurosurgery of Tongling People′s Hospital and Tongling Municipal Hospital from June 2016 to February 2021. According to the difference of prognosis, the patients were divided into good prognosis group( n=34) and poor prognosis group( n=62). The clinical data of the two groups were compared. Such as sex, age, basic disease (years of hypertension, diabetes), GCS score at admission, arterial systolic blood pressure at admission, blood glucose at admission, volume of cerebral parenchyma hemorrhage, whether there was a reexamination of head CT within 1 hour before operation, whether there was intraventricular hemorrhage, postoperative complications (pulmonary infection, intracranial infection, rebleeding), GOS score 1 month after operation.The metrological data of normal distribution were expressed by mean ± standard deviation ( ± s). Independent t test was used for comparison between groups. Chi-square test was used for comparison of counting data. Multivariate Logistic regression analysis was used to screen independent risk factors for short-term prognosis after minimally invasive surgery. Results:Among the 96 patients, Univariate analysis showed that there were significant differences in age, diabetes, admission GCS score, arterial systolic blood pressure (SBP), blood glucose at admission, head CT within 1 hour before operation, intraventricular hemorrhage, timing of operation and number of postoperative complications between the two groups. Multivariate Logistic regression analysis showed that age >75 years old( OR=4.358, 95% CI: 1.209-15.710), diabetes mellitus( OR=4.637, 95% CI: 1.793-11.990), admission GCS score≤ 8( OR=14.305, 95% CI: 2.694-75.950), blood glucose ≥10.0 mmol/L at admission( OR=3.229, 95% CI: 1.261-8.270), no reexamination of head CT within 1 hour before operation( OR=9.423, 95% CI: 1.827-48.599), intraventricular hemorrhage( OR=12.109, 95% CI: 3.336-43.961), operation time > 7 hours( OR=6.234, 95% CI: 1.986-19.570), the number of postoperative complications ≥ 2( OR=13.461, 95% CI: 3.624-49.999)were independent risk factors for short-term prognosis. Conclusions:Minimally invasive treatment of elderly hypertensive basal ganglia intracerebral hemorrhage can achieve satisfactory clinical outcomes. However, age >75 years old, diabetes, admission GCS score≤ 8, blood glucose ≥10.0 mmol/L at admission, no reexamination of head CT within 1 hour before operation, with intraventricular hemorrhage, operation time > 7 hours, the number of postoperative complications ≥ 2 are independent risk factors affecting short-term prognosis of patients. It is necessary to strengthen the perioperative management of patients, which is of great significance to improve the prognosis.

Research progress on pesticide residues of Panax notoginseng / 中国中药杂志

Panax notoginseng is a perennial Chinese medicinal plant, which has serious continuous cropping obstacles and is prone to a variety of diseases and insect pests during the growth process. At present, the prevention and control of pests and diseases is mainly carried out through chemical pesticides, and the consequent pesticide residues of P. notoginseng have attracted much attention. This study reviewed the types and detection methods of pesticide residues in P. notoginseng from 1981 to 2021, and compared the limits of pesticide residues in P. notoginseng in China and abroad to provide a reference for rational application of pesticides in P. notoginseng and quality control of medicinal materials, thereby promoting the sustainable development of the P. notoginseng industry in China. Currently, there are only 40 published papers on pesticide residues of P. notoginseng, which is indicative of a serious problem of insufficient research. At present, hundreds of pesticide residues in P. notoginseng can be detected simultaneously by using chromatography-tandem mass spectrometry. The pesticides detected have gradually changed from early prohibited ones, such as dichlorodiphenyl trichloroethane(DDT), benzene hexachloride(BHC), and parathion, to low toxic ones(e.g., dimethomorph, procymidone, propicona-zole, and difenoconazole). The dietary risk from pesticide residues in P. notoginseng is low, which would not cause harm to consu-mers. This study concluded that in the future, the development of the quality standard for pesticide residues of P. notoginseng should be actively carried out. To increase the pesticides used in actual production in the quality standard based on the existing ones and to guide farmers to use pesticides scientifically will be the focus of future work.

Effects of chloropicrin fumigation on soil and growth and development of Panax notoginseng / 中国中药杂志

The continuous cropping obstacle of Panax notoginseng is serious, and effective control measures are lacking. Soil disinfection with chloropicrin(CP) has been proven to be effective in reducing the obstacles to continuous cropping of other crops. In order to ascertain the effect of CP in the continuous cropping of P. notoginseng, this paper explored the influences of CP at different treatment concentrations(0,30,40,50 kg/Mu, 1 Mu≈667 m~2) on soil macro-element nutrients, soil enzyme activity, growth and development of P. notoginseng, and the accumulation of medicinal components. The results showed that CP fumigation significantly increased the content of total nitrogen, alkali-hydrolyzable nitrogen, ammonium nitrogen, nitrate nitrogen, and available phosphorus in the soil, but it had no significant effect on potassium content. The soil protease activity showed a trend of first increasing and then decreasing with the prolonging of the treatment time. Both the soil urease and acid phosphatase activities showed a trend of first decreasing and then increasing with the prolonging of the treatment time. The higher the CP treatment concentration was, the lower the urease and acid phosphatase activities would be in the soil. The protease activity was relatively high after CP40 treatment, which was better than CP30 and CP50 treatments in promoting the nitrogen-phosphorus-potassium accumulation in P. notoginseng. The seedling survival rates after CP0, CP30, CP40, and CP50 tratments in October were 0, 65.56%, 89.44%, and 83.33%, respectively. Compared with the CP30 and CP50 treatments, CP40 treatment significantly facilitated the growth and development of P. notoginseng, the increase in fresh and dry weights, and the accumulation of root saponins. In summary, CP40 treatment accelerates the increase in soil nitrogen and phosphorus nutrients and their accumulation in P. notoginseng, elevates the seedling survival rate of P. notoginseng, enhances the growth and development of P. notoginseng, and promotes the accumulation of medicinal components. CP40 treatment is therefore recommended in production.

Contributions and strategies of eco-agriculture of Chinese medicine services for carbon dioxide peaking and carbon neutrality / 中国中药杂志

Carbon dioxide peaking and carbon neutrality have become hot issues of political and economic activities in China and abroad. The structure and development of various industries in China will be profoundly affected in the process of accomplishing "Dual Carbon" goals. Eco-agriculture of Chinese medicine(EACM) highlights the balance and sustainable development of the ecosystem while producing high-quality medicinal materials. With chemically synthesized fertilizers, pesticides, and growth regulators prohibited, EACM emphasizes the recycling of agricultural and sideline products and the reduction of waste output, which results in the minimal negative impact on the ecological environment. Therefore, it is typical agriculture with low-carbon sources and high-carbon sinks. This study reviewed the mechanism and potential of EACM in carbon dioxide peaking and carbon neutrality, analyzed the specific ways of EACM in reducing carbon sources and increasing carbon sinks based on the typical ecological planting pattern, and proposed the point of view to strengthen EACM as well as the "Dual Carbon" theory and research methods, so as to direct low-carbon and efficient deve-lopment. Furthermore, this study advocated to comprehensively promote the transformation of Chinese medicine production from chemical agriculture to eco-agriculture to improve the comprehensive benefits of contribution rate of carbon neutrality, explore and establish carbon sink compensation mechanism to ensure the sustainable and healthy development of EACM, and strengthen the training of EACM and "Dual Carbon" theory and technologies to continuously improve the capacity of EACM in sustainable development. This study is expected to provide a reference for the development of ecological functions in EACM and the development of economic functions through ecological functions.

Subchronic Oral Toxicity Evaluation of Sodium Dehydroacetate: A 90-day Repeated Dose Study in Rats / 生物医学与环境科学（英文）

Objective@#The present study was undertaken to evaluate the subchronic oral toxicity of sodium dehydroacetate (DHA-Na) and to determine the point of departure (POD), which is a critical factor in the establishment of an acceptable dietary intake.@*Methods@#DHA-Na was administered once daily by gavage to Sprague-Dawley rats at dose levels of 0.0, 31.0, 62.0, and 124.0 mg/kg BW per day for 90 days, followed by a recovery period of 4 weeks in the control and 124.0 mg/kg BW per day groups. The outcome parameters were mortality, clinical observations, body weights, food consumption, hematology and clinical biochemistry, endocrine hormone levels, and ophthalmic, urinary, and histopathologic indicators. The benchmark dose (BMD) approach was applied to estimate the POD.@*Results@#Significant decreases were found in the 62.0 and 124.0 mg/kg BW groups in terms of the body weight and food utilization rate, whereas a significant increase was found in the thyroid stimulating hormone levels of the 124.0 mg/kg BW group. Importantly, the 95% lower confidence limit on the BMD of 51.7 mg/kg BW was modeled for a reduction in body weight.@*Conclusion@#The repeated-dose study indicated the slight systemic toxicity of DHA-Na at certain levels (62.0 and 124.0 mg/kg BW) after a 90-day oral exposure.

Efficacy observation of the caudal-medial approach combined with "page-turning" middle lymphadenectomy in the laparoscopic right hemicolectomy / 中华胃肠外科杂志

Objective: To investigate the safety and feasibility of caudal-medial approach combined with "page-turning" middle lymphadenectomy in the laparoscopic right hemicolectomy. Methods: A descriptive cohort study was conducted. Clinical data of 35 patients who underwent laparoscopic radical right hemicolectomy using caudal-medial approach combined with "page-turning" middle lymphadenectomy at Department of Gastrointestinal Surgery, Guangdong Hospital of Chinese Medicine from April 2018 to May 2020 were retrospectively analyzed. All operations were performed consecutively by the same surgeon. The caudal-medial approach was used to dissect the right Toldt's fascia and the anterior pancreaticoduodenal space in a caudal-to-cranial and medial-to-lateral manner guided by the duodenum. The "page-turning" middle lymphadenectomy was used to dissect the mesocolon along the superior mesenteric vein with ileocolic vein, Henle's trunk and pancreas exposed preferentially. Results: All the 35 patients completed the operation successfully, and there was no damage and bleeding of superior mesenteric vessels and their branches. The operative time was (186.9±46.2) minutes, and the blood loss was 50 (10-200) ml. The first time to flatus was (2.1±0.6) days, and the time to fluid intake was (2.5±0.8) days. The postoperative hospital stay was 6 (3-18) d. The overall morbidity of postoperative complication was 8.6% (3/35), including grade II in 1 cases (2.8%) and grade IIIa in 2 case (5.7%) according to the Clavien-Dindo grading standard. The total number of lymph node dissected was 30.2±5.6, and the positive lymph node was 0 (0-7). Tumor staging revealed 5 cases of stage I, 18 cases of stage II, 11 cases of stage III, and 1 case of stage IVA. In this study, the median follow-up time was 15 (4-29) months. One patient died due to cerebrovascular accident 12 months after surgery, and no tumor recurrence or metastasis was observed in all other patients. Conclusions: Laparoscopic radical right hemicolectomy using caudal-medial approach combined with "page-turning" middle lymphadenectomy is safe and feasible. The anterior pancreaticoduodenal space is preferentially mobilized, which reduces the difficulty of central vascular dissection.

Five-step maneuver of transthoracic single-port assisted laparoscopic lower mediastinal lymph node dissection for Siewert type Ⅱ adenocarcinoma of the esophagogastric junction / 中华胃肠外科杂志

Objective: Surgical operation is the main treatment for advanced adenocarcinoma of esophagogastric junction (AEG). Due to its special anatomic location and unique lymph node reflux mode, the surgical treatment of Siewert II AEG is controversial. Lower mediastinal lymph node dissection is one of the most controversial points and a standard technique has not yet been established. This study is aim to explore the safety and feasibility of five-step maneuver of transthoracic single-port assisted laparoscopic lower mediastinal lymph node dissection for Siewert type II AEG. Methods: A descriptive case series study was conducted. The intraoperative and postoperative data of 25 patients with Siewert type II AEG who underwent five-step maneuver of transthoracic single-port assisted laparoscopic lower mediastinal lymph node dissection in Guangdong Provincial Hospital of Traditional Chinese Medicine from January 2019 to April 2021 were retrospectively analyzed. Five-step maneuver was as follows: In the first step, the subcardiac sac was exposed; the right pulmonary ligament lymph nodes and the anterior thoracic paraaortic lymph nodes were dissected cranial to inferior pericardium, left to left edge of thoracic aorta. In the second step, the left diaphragm was opened, and a 12 mm trocar was placed through the 6-7 rib in the left anterior axillary line. The supra-diaphragmatic nodes were dissected through the thoracic operation hole. In the third step, the left inferior pulmonary ligament was severed. The anterior fascia of thoracic aorta was incised to join the anterior space of thoracic aorta formed in the first step and then the lymphatic tissue was dissected upward until the exposure of left inferior pulmonary vein. In the fourth step, the posterior pericardium was denuded retrogradely from ventral side to oral side to the level of left inferior pulmonary vein, right to right pleura, and then the right pulmonary ligament lymph nodes were completely removed. In the fifth step, the esophagus was denuded, and the esophagus was transected 5 cm above the tumor using a linear stapler to complete the dissection of lower thoracic paraesophageal lymph nodes. Results: Operations were successfully completed in 25 patients without conversion, intra-operative complication and perioperative death. Total gastrectomy was performed in 19 cases and proximal gastrectomy in 6 cases. The mean operative time was (268.7±85.6) minutes, the mean estimated blood loss was (90.4±44.2) ml, the mean time of lower mediastinal lymph node dissection was (38.6±10.3) minutes, and the mean harvested number of lower mediastinal lymph node was 5.9±2.9. The length of esophageal invasion was >2 cm in 7 cases and ≤ 2 cm in 18 cases. Eight patients (33.0%) had lower mediastinal lymph node metastasis, including 3 cases with esophageal invasion >2 cm and 5 cases with esophageal invasion ≤ 2 cm. The mean time to postoperative first flatus was (5.5±3.1) days. The average time of postoperative thoracic drainage was (5.9±2.9) days. The mean hospital stay was (9.7±3.1) days. Two patients (8.0%) developed postoperative grade IIIa complications according to the Clavien-Dindo classification, including 1 case of pancreatic fistula and 1 case of pleural effusion, both of whom were cured by puncture drainage. Conclusions: Five-step maneuver of transthoracic single-port assisted laparoscopic lower mediastinal lymph nodes dissection for Siewert type II AEG is safe and feasible. Which can ensure sufficient lower mediastinal lymph node dissection to the level of left inferior pulmonary vein.

Effect of total body 137Cs γ-irradiation on the m 6A modification profile of circRNA in mouse bone marrow cells / 中华放射医学与防护杂志

Objective:To investigate the effect of ionizing radiation on the N 6-methyladenine (m 6A) modification profile of circular RNA (circRNA) in mouse bone marrow cells and provide scientific basis for revealing the relationship between RNA epigenetic modification and hematopoietic radiation injury. Methods:A total of twenty four C57BL/6 J mice were randomly divided into two groups: the healthy control group ( n=12), and ionizing radiation group ( n=12) irradiated in total body with 4 Gy of 137Cs γ-rays. At 5 min after irradiation, mice were killed and bone marrow cells were collected from the femur. Total RNAs were extracted and the changes in circRNA m6A modification profiles were investigated by RNA immunoprecipitation-high-throughput sequencing (MeRIP-Seq) technology and bioinformatics analysis. The representative alterations of m 6A peaks were validated by MeRIP-PCR assay. Results:325 and 455 m 6A sites were identified on circRNAs in the healthy control group and ionizing radiation group (178 common sites, 147 specific sites in the healthy control group and 277 specific sites in ionizing radiation group), respectively. 1 275 and 1 017 deriving genes of m 6A-circRNAs were identified in the healthy control group and ionizing radiation group (767 common genes, 508 specific genes in the healthy control group and 250 specific genes in ionizing radiation group), respectively. Compared with the control healthy group, 414 (178) m 6A peaks was significantly up- (down-) regulated in the ionizing radiation group( P < 10 -10; fold-change cut-off > 5). Moreover, Gene Ontology (GO) assay revealed that the deriving genes of circRNAs with differentially methylated m 6A sites between two groups involves various functions including chromatin regulation, ciliary transition fiber and poly (A)-specific ribonuclease activity. Kyoto Encyclopedia of Genes and Genomes (KEGG) assay revealed that the deriving genes of circRNAs with differentially methylated m 6A sites between two groups included numerous pathways such as platelet activation, Fc γ R-mediated phagocytosis and B cell receptor signaling pathway. Conclusions:Ionizing radiation triggers rapid alterations in the m 6A modification profile of circRNA in mouse bone marrow cells. The deriving genes of differentially methylated circRNAs are associated with a variety of functions and signaling pathways of hematopoietic radiobiology.

Effects of Tween-80 and butyric acid on radiation-induced bile acid enterohepatic circulation disturbance and the treatment strategy / 中华放射医学与防护杂志

Objective:To study the effect of emulsifier Tween-80 on radiation-induced bile acid enterohepatic circulation disturbance and the treatment strategy.Methods:Male C57BL/6 J mice were randomly divided into healthy control group, radiation-only group, radiation + Tween-80 group and radiation + Tween-80 + butyric acid group. The mice were exposed to total abdominal irradiation (TAI) using a specific steel lead chamber and γ-ray irradiator was used throughout the experiments. Mice in radiation+ Tween-80 group and radiation+ Tween-80+ butyric acid group were intragastrically administrated with Tween-80 for 7 d before irradiation, while healthy control group and radiation-only group were treated with sterile water. After irradiation, butyric acid was administrated to mice in radiation+ Tween-80+ butyric acid group until euthanasia, while healthy control group, radiation-only group and radiation+ Tween-80 group were treated with sterile water until euthanasia. Small intestine and fecal particles were collected 21 d after irradiation. The concentrations of bile acid in small intestinal and fecal samples were measured using enzyme linked immunosorbent assay (ELISA), the expression of TGR5 and JAM-A, as well as the ratio of IL-10/IL-12 in intestine were detected by quantitative real-time PCR (qRT-PCR). The expression levels of GPR43 in the colon were compared using immunohistochemistry (IHC).Results:Tween-80 pretreated mice exhibited lower concentration of bile acid in small intestine and higher level of bile acid in fecal sample after irradiation (7.92%, 7.99%, t=3.93, 2.94, P<0.05), the expression of TGR5, which mediating the biological function of bile acid, and it′s downstream JAM-A gene were down-regulated (20.93%, 9.91%, t=4.85, 5.14, P<0.05), the ratio of IL-10/IL-12 (indicator related to inhibition of inflammation) (4.59%, t=3.39, P<0.05) as well as the expression of GPR43 protein, a G-protein-coupled receptor for butyric acid, decreased in the colon of Tween-80-pretreated mice compared with the radiation-only group. ELISA assay revealed that butyric acid administration elevated bile acid level in small intestines (8.06%, t=9.25, P<0.05), but reduced that in feces (14.41%, t=4.71, P<0.05). In addition, TGR5 and JAM-A showed higher expression in the intestine of butyric acid-treated mice (19.35%, 32.71%, t=7.69, 19.23, P<0.05), as well as the ratio of IL-10/IL-12 (2.39%, 4.05%, t=3.38, 5.92, P<0.05) and the content of GPR43 protein in colon. Conclusions:Tween-80 deteriorates the disturbance of bile acid enterohepatic circulation induced by ionizing radiation in mice. Butyric acid administration erases the adverse effects of Tween-80.

Research advances of precision treatment for pancreatic cancer / 中华消化外科杂志

Pancreatic cancer is the third leading cause of cancer-related death in the world due to its high malignancy, difficult in early diagnosis, poor treatment efficacy, and high mortality. In recent years, benefiting from the progress of combined chemotherapy and neoadjuvant therapy, the prognosis of patients with pancreatic cancer has been improved to a certain extent. However, compared with other tumors, progress of precision medicine in pancreatic cancer is slow. The authors introduce the latest progress and difficulties in precision medicine of pancreatic cancer including molecular classification based on single gene and omics, monitoring tumor progression and guide treatment by minimally invasive liquid biopsy, as well as targeting therapy and immuno-therapy, in order to accelerate the development of precision medicine of pancreatic cancer.