One of the leading therapies for acute lymphoblastic leukemia (ALL) is the chemotherapeutic agent PEGylated E. coli-derived-l-asparaginase (PEG-ASNase). Due to the high risk of dose-limiting liver injury, characterized by clinically elevated levels of hepatic transaminases, PEG-ASNase therapy is generally avoided in adult patients. Our preclinical investigations have indicated that PEG-ASNase-induced liver injury is associated with the release of free fatty acids (FFAs) from white adipose tissue (WAT), suggesting potential lipotoxic effects. However, it remains uncertain whether PEG-ASNase directly induces hepatotoxicity or sensitizes hepatocytes to FFA-induced toxicity. Our results show that PEG-ASNase treatment results in hepatocyte apoptosis and lipid peroxidation. Ex vivo and in vitro studies in mouse and human WAT suggest that PEG-ASNase induces the expression of adipose triglyceride lipase (ATGL), activates the lipase, and stimulates adipose tissue lipolysis, suggesting that the FFAs from WAT may contribute to the observed liver injury. Moreover, treatment with PEG-ASNase sensitizes hepatocytes to FFA-induced lipotoxicity. Mechanistically, our RNA-sequencing (RNA-seq) analyses reveal that PEG-ASNase-induced sensitization to lipotoxicity is accompanied by the induction of Cyp2e1. We demonstrated that this sensitization effect is attenuated by both pharmacological and genetic inhibition of Cyp2e1. Our findings suggest that PEG-ASNase therapy induces WAT lipolysis and sensitizes hepatocytes to hepatic lipotoxicity in a Cyp2e1-dependent manner.

Transmembrane proteins(TMEMs)are a class of family proteins that span lipid bilayers,serving as crucial channel proteins on biological membranes,playing essential physiological roles.TMEMs′ over-expression in malignant tumors,such as TMEM16A and TMEM206,has been linked to the promotion of malignancy.Conversely,down-regulation of TMEM100 expression has been associated with tumor progression.TMEM98,whose expression varies across different malignancies.TMEMs has shown promise as both a therapeutic target and a prognostic marker in cancer.Additionally,TMEMs play a vital role in various malignancies by modulating the Wnt and AKT signaling pathways through interaction with different upstream and downstream regulatory factors.Furthermore,research has provided additional insights into their role in cisplatin-related chemoresistance in specific malignant tumor cell populations.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has spread worldwide and threatened human's health. With the passing of time, the epidemiology of coronavirus disease 2019 evolves and the knowledge of SARS-CoV-2 infection accumu-lates. To further improve the scientific and standardized diagnosis and treatment of maternal SARS-CoV-2 infection in China, the Chinese Society of Perinatal Medicine of Chinese Medical Association commissioned leading experts to develop the Recommendations for the Diagnosis and Treatment of Maternal SARS-CoV-2 Infection under the guidance of the Maternal and Child Health Department of the National Health Commission. This recommendations includes the epidemiology, diagnosis, management, maternal care, medication treatment, care of birth and newborns, and psychological support associated with maternal SARS-CoV-2 infection. It is hoped that the recommendations will effectively help the clinical management of maternal SARS-CoV-2 infection.

SARS-CoV-2 is an emerging viral pathogen and a major global public health challenge since December of 2019, with limited effective treatments throughout the pandemic. As part of the innate immune response to viral infection, type I interferons (IFN-I) trigger a signaling cascade that culminates in the activation of hundreds of genes, known as interferon stimulated genes (ISGs), that collectively foster an antiviral state. We report here the identification of a group of type I interferon suppressed genes, including fatty acid synthase (FASN), which are involved in lipid metabolism. Overexpression of FASN or the addition of its downstream product, palmitate, increased viral infection while knockout or knockdown of FASN reduced infection. More importantly, pharmacological inhibitors of FASN effectively blocked infections with a broad range of viruses, including SARS-CoV-2 and its variants of concern. Thus, our studies not only suggest that downregulation of metabolic genes may present an antiviral strategy by type I interferon, but they also introduce the potential for FASN inhibitors to have a therapeutic application in combating emerging infectious diseases such as COVID-19.

Objective:To investigate the effect of everting resection natural orifice specimen extraction surgery (NOSES) on postoperative function in patients with colorectal cancer.Methods:The clinical data of 78 patients with colorectal cancer treated in Chongqing Bishan District People's Hospital from June 2019 to June 2020 were retrospectively analyzed. According to the selected surgical methods, they were divided into the study group (45 cases) and the control group (33 cases). The control group underwent traditional laparoscopic radical resection of colorectal cancer, and the study group underwent everting resection NOSES. Perioperative indicators such as intraoperative bleeding, operation time, postoperative exhaust time and hospitalization time were observed in the two groups. Anal function indicators [anal constriction pressure, fecal incontinence severity score (Wexner score)], coagulation function indicators [activated partial thromboplastin time (APTT), prothrombin time (PT)], the levels of inflammatory factors [interleukin-6 (IL-6), C-reactive protein (CRP)] and pain factors [nerve growth factor (NGF), prostaglandin E2 (PGE2), neuropeptide Y (NPY)] before and after operation were compared between the two groups.Results:There were no significant differences in intraoperative bleeding and operation time between the two groups ( t values were 1.30 and 0.56, both P > 0.05); the postoperative exhaust time and hospitalization time of the study group were shorter than those of the control group ( t values were 26.88 and 7.42, both P < 0.05). At 3 months after operation, the anal constriction pressure in the two groups was lower than that before operation [study group: (177±10) mmHg (1 mmHg = 0.133 kPa) vs. (184±10) mmHg, t = 3.22, P < 0.001; control group: (178±10) mmHg vs. (184±10) mmHg, t = 2.36, P = 0.020]; the Wexner score was higher than that before operation [study group: (9.0±1.2) points vs. (7.9±1.2) points, t = 4.26, P < 0.001; control group: (10.3±1.2) points vs. (7.9±1.2) points, t = 7.80, P < 0.001], and the Wexner score in the study group was lower than that in the control group ( t = 4.57, P < 0.001). At 1 day after operation, APTT and PT in the two groups were shorter than those before operation (all P < 0.05), and APTT and PT in the study group were shorter than those in the control group [APTT: (26.2±2.2) s vs. (28.3±2.2) s, t = 4.23, P < 0.001; PT: (9.34±0.17) s vs.(11.03±0.41) s, t = 24.93, P < 0.001]. At 1 day after operation, the levels of IL-6 and CRP in the two groups were higher than those before operation (all P < 0.05); the levels of IL-6 and CRP in the study group were lower than those in the control group [IL-6: (8.6± 2.2) ng/L vs. (17.2±3.1) ng/L, t = 14.26, P < 0.001; CRP: (2.16±0.22) mg/L vs. (2.99±0.24) mg/L, t = 15.84, P < 0.001]. At 1 day after operation, the levels of NGF, PGE2 and NPY in the two groups were higher than those before operation (all P < 0.05), and the levels of NGF, PGE2 and NPY in the study group were lower than those in the control group [NGF: (302±7) pg/ml vs. (319±8) pg/ml, t = 9.76, P < 0.001; PGE2: (189±4) ng/L vs. (196±5) ng/L, t = 6.56, P < 0.001; NPY: (164±10) ng/L vs. (177±11) ng/L, t = 5.36, P < 0.001]. Conclusions:Everting resection NOSES can effectively shorten the postoperative exhaust time and hospitalization time of patients with colorectal cancer, have less impact on coagulation function and anal function, reduce the inflammatory reaction and the level of pain factors.

Objective:To compare the efficacy and prognosis between fluorescent laparoscopic and conventional laparoscopic radical resection of colorectal cancer.Methods:A total of 114 colorectal cancer patients in Bishan District People's Hospital of Chongqing from June 2019 to January 2021 were selected as the research objects, and they were divided into two groups according to the diagnosis and treatment time. Forty-four patients receiving treatment from June 2019 to February 2020 were enrolled as group A, and 70 patients receiving treatment from March 2020 to January 2021 were set as group B. Patients in group A received fluorescent laparoscopic radical resection of colorectal cancer, and patients in group B received conventional laparoscopic radical resection of colorectal cancer. The operation time, intraoperative blood loss, metastatic lymph node clearance rate, clinical efficacy (the overall response rate was calculated as complete remission + partial remission), postoperative complication rate and recurrence rate within 1 year were compared between the two groups.Results:The clearance rate of metastatic lymph nodes was 86.95% (40/46) in group A, which was higher than 72.22% (52/72) in group B, and the difference was statistically significant ( χ2 = 3.55, P = 0.049). There were no statistical differences in operation time and intraoperative blood loss between the two groups (all P > 0.05). The overall response rate was 86.36% (38/44) in group A, which was higher than 74.28% (52/70) in group B, and the difference was statistically significant ( χ2 = 5.03, P = 0.024). The incidence of complications in group A was 9.09% (4/44), which was not significantly different from that in group B (11.42%,8/70) ( χ2 = 0.16, P = 0.692). The recurrence rate within 1 year of group A was 11.36% (5/44), which was lower than that of group B (24.42%, 15/70), but the difference was not statistically significant ( χ2 = 1.89, P = 0.169). Conclusions:Compared with conventional laparoscopy, fluorescent laparoscopic radical resection of colorectal cancer has better clinical efficacy, higher clearance rate of metastatic lymph nodes, and does not increase the incidence of postoperative metastasis and complications.

Objective:To compare the clinical efficacy of two-dimensional (2D) fluoroscopic guided robot-assisted and conventional TESSYS surgery in the treatment of lumbar disc herniation, the feasibility and precautions of 2D fluoroscopic guided robot-assisted TESSYS surgery were discussed.Methods:A retrospective analysis was performed on 34 male and 36 female patients aged 44.57±6.10 years (range 27 to 60 years) who received 2D guided robot-assisted TESSYS surgery and conventional TESSYS surgery from July 2019 to April 2020. 2D guided robot assisted TESSYS surgery group (the robot group) 32 cases, conventional TESSYS surgery (the conventional group) 38 cases. The number of puncture, number of fluoroscopy, puncture-channel time, operation time, visual analogue scale (VAS) and Oswestry disability index (ODI) before and after surgery and at the last follow-up were compared between the two groups to verify the clinical efficacy, and the complications were analyzed.Results:There were no significant differences in age, gender, body mass index, surgical level, Michigan State University (MSU) grading and average follow-up time between the robot group and the conventional group (all P>0.05). All patients completed surgery. The number of puncture times was 1.22±0.79 in the robot group and 4.66±1.86 in the conventional group, and the difference was statistically significant ( t=10.320, P<0.001). The number of fluoroscopy in the robot group was 10.97±1.96 times, and that in the conventional group was 17.45±4.30 times, the difference was statistically significant ( t=8.313, P<0.001). The puncture-channel time of the robot group was 10.66±3.62 min and that of the conventional group was 20.21±5.47 min, and the difference was statistically significant ( t=8.446, P<0.001). The operation time of the robot group was 62.25±6.68 min, and that of the conventional group was 72.89±10.48 min, the difference was statistically significant ( t=4.956, P<0.001). VAS scores of the robot group were 6.91±0.93 points before surgery, 2.97±0.65 points 1 d after surgery, and 1.53±0.51 points at the last follow-up, while those of the conventional group were 7.29±1.14 points before surgery, 2.89±0.56 points 1 d after surgery, and 1.42±0.50 points at the last follow-up. The ODI index of the robot group was 40.13%±1.54% before surgery, 17.28%±1.69% 1 day after surgery, and 10.84%±1.25% at the last follow-up, while that of the conventional group was 40.03%±1.46% before surgery, 17.42%±2.45% 1 day after surgery, and 10.92%±1.17% at the last follow-up. There were no statistically significant differences (all P>0.05). Two patients (6.3%) in the robot group and four (10.5%) in the conventional group had residual disc, there was no significant difference ( P>0.05). Conclusion:2D guided robot assisted TESSYS surgical treatment of lumbar disc herniation, which can plan puncture path in the stage of percutaneous target puncture, rigid guidance and accurate puncture target, and has obvious advantages in reducing puncture times and fluoroscopy times.

Objective:To compare the early and mid-term results of hybrid coronary revascularization (HCR) and minimally invasive multivessel coronary artery bypass grafting (MICS-CABG) in coronary artery disease patients with low left ventricular ejection fraction and non diabetes mellitus, and to explore the indication of HCR and MICS-CABG.Methods:A retrospective cohort analysis of HCR and MICS-CABG cases with preoperative left ventricular ejection fraction less than 0.40, and without diabetes mellitus were conducted in Xijing Hospital from January 2015 to December 2019. 36 cases in HCR group and 17 cases in MICS group were included in this study. For HCR procedure, minimally invasive left internal mammary artery(LIMA) to the left anterior descending artery (LAD) bypass surgery were performed, and followed by percutaneous coronary intervention (PCI) to treat non LAD lesion 1 to 4 weeks later. MICS-CABG procedure was performed through left anterior small thoracotomy minimally invasive direct coronary artery bypass grafting for multiple diseased vessels.Results:The preoperative SYNTAX score in MICS group was significantly higher than that in HCR group ( P<0.05). There was no perioperative death in both groups. Troponin I, postoperative drainage volume, blood transfusion volume and ventilator ventilation time in MICS group were significantly higher than those in HCR group ( P<0.05). After 12 months follow-up, no patient died in both groups. Furthermore, all LIMA grafts were patency. The stenosis rate of drug-eluting stents in HCR group was similar to that of great saphenous vein grafts in MICS group. LVEF and left ventricular end diastolic diameter of both groups were significantly improved 12 months after operation ( P<0.05). Conclusion:HCR and MICS-CABG are minimally invasive and safe treatment for multivessel coronary artery disease patients with low ejection fraction and non diabetese mellitus. The early and mid-term therapeutic effects are satisfactory. If coronary artery lesions other than LAD are suitable for PCI, HCR should be the preferred treatment.

Objective:To evaluate the risk factors of acute kidney injury (AKI) in patients with multiple wasp stings.Methods:Patients with multiple wasp stings were retrospectively enrolled in Hanzhong Central Hospital from September 2010 to November 2020. Based on whether the patients developed AKI, the patients were divided into AKI group and non-AKI group. The general characteristics and laboratory examinations between the two groups were compared. The logistic regression model was used to analyze the risk factors of AKI.Results:A total of 356 patients with multiple wasp stings were recruited in this study, with 196 males (55.1%). The age was 56.0(45.0, 64.0) years old. There were 59 patients (16.6%) with hypertension and 13 patients (3.6%) with diabetes. There were 51 patients (14.3%) in the AKI group and 305 patients (85.7%) in the non-AKI group. Baseline data and biochemical examinations indicated that the two groups showed significant differences in gender, age, sting sites (systemic or local), sting needles, proportions of gross hematuria, leukocyte count, hemoglobin, creatine kinase, alanine transaminase, aspartate aminotransferase, total bilirubin, proportions of urinary protein, and proportions of urine occult blood (all P<0.05). The multivariate logistic regression analysis results showed that the increasing number of sting needles (every 10 needles increase, OR=1.866, 95% CI 1.289-2.071, P=0.001), gross hematuria ( OR=9.770, 95% CI 2.586-36.910, P=0.001), decreasing hemoglobin (every 1 g/L increase, OR=0.016, 95% CI 0.001-0.355, P=0.009), increasing aspartate aminotransferase (every 100 U/L increase, OR=1.311, 95% CI 1.144-1.502, P<0.001), and increasing total bilirubin (every 10 μmol/L increase, OR=1.200, 95% CI 1.008-1.430, P=0.041) were independent influencing factors of AKI. Conclusions:The increasing number of sting needles, gross hematuria, decreasing hemoglobin, increasing aspartate aminotransferase, and increasing total bilirubin are independent risk factors of AKI in patients with multiple wasp stings.

One of the distinct characters of Latrodectus tredecimguttatus is that its toxic components exist not only in the venomous glands, but also in the tissues outside the venomous glands and even in the eggs. Investigation on the toxins outside the venomous glands can deepen our understanding of spider toxins and discover new lead molecules with important application prospects. In order to explore the low-abundance proteinaceous toxins in the L. tredecimguttatus eggs, we used bioinformatic strategies to mine a gene sequence encoding a peptide toxin from the transcriptome of L. tredecimguttatus eggs, and then heterologously expressed the gene successfully with a 3'-RACE combined with nest PCR strategy. Biological activity analyses indicated that the expressed peptide toxin, named latroeggtoxin-Ⅵ (LETX-Ⅵ), could inhibit Na⁺ channel currents in ND7/23 cells and promote dopamine release from PC12 cells, without obvious toxicity against Periplaneta americana and bacteria as well as fungi including Staphylococcus aureus and Candida albicans, demonstrating that LETX-Ⅵ is a mammal-specific neurotoxin with a potential application prospect in development of the tool reagents for neurobiological study and the drugs for treating related diseases.
Animals ; Arthropod Proteins/genetics* ; Black Widow Spider/genetics* ; Cloning, Molecular ; Rats ; Spider Venoms/genetics* ; Transcriptome