Elemene is widely recognized as an effective anti-cancer compound and is routinely administered in Chinese clinical settings for the management of several solid tumors, including non-small cell lung cancer (NSCLC). However, its detailed molecular mechanism has not been adequately demonstrated. In this research, it was demonstrated that elemene effectively curtailed NSCLC growth in the patient-derived xenograft (PDX) model. Mechanistically, employing high-throughput screening techniques and subsequent biochemical validations such as microscale thermophoresis (MST), microRNA-145-5p (miR-145-5p) was pinpointed as a critical target through which elemene exerts its anti-tumor effects. Interestingly, elemene serves as a binding stabilizer for miR-145-5p, demonstrating a strong binding affinity (dissociation constant (K _D) = 0.39 ± 0.17 μg/mL) and preventing its degradation both in vitro and in vivo, while not interfering with the synthesis of the primary microRNA transcripts (pri-miRNAs) and precursor miRNAs (pre-miRNAs). The stabilization of miR-145-5p by elemene resulted in an increased level of this miRNA, subsequently suppressing NSCLC progression through the miR-145-5p/mitogen-activated protein kinase kinase kinase 3 (MAP3K3)/nuclear factor kappaB (NF-κB) pathway. Our findings provide a new perspective on revealing the interaction patterns between clinical anti-tumor drugs and miRNAs.

Objective:To investigate the effect of electroacupuncture treatment on the integrity of myelin and the related molecules in the spinal dorsal horn of neuropathic pain model rat.Methods:Totally 32 SPF grade Sprague-Dawley rats were randomly divided into 4 groups: sham group, pain model group, electroacupuncture group and sham electroacupuncture group, with 8 rats in each group. Neuropathic pain model was established by right sciatic nerve ligation. Electroacupuncture stimulation of Huantiao point and Yanglingquan point was started from 1 day after surgery, 30 min/d, and lasted for 14 days. The paw withdraw mechanical threshold (PWMT) were tested before surgery, 3 days, 7 days and 14 days after surgery. Immunofluorescence was used to detect myelin basic protein (MBP) in the ipsilateral Ⅰ-Ⅲ laminae of spinal dorsal horn and Western blot was used to measure the expression of β-secreatase 1(BACE1), neuregulin 1 type Ⅲ (NRG1 Ⅲ) and phosphorylated ErbB receptor tyrosine kinase 2 (p-ErbB2) at 14 days after surgery.SPSS 24.0 was used for statistical analysis.Repeated measurement ANOVA was used for behavioral analysis and one-way ANOVA followed by Bonferroni test was used for Western blot and immunofluorescence data analysis.Results:(1) The results of pain behaviors showed that the interaction effect of time and group on PWMT was significant ( F=29.817, P<0.001), and both the time main effect ( F=240.598, P<0.001) and group main effect ( F=304.291, P<0.001) were significant. There were no significant differences among 4 groups before surgery. Compared with pain model group, the PWMT of electroacupuncture group were significantly increased at 3 days ((16.87±1.82) g, (11.31±1.36) g), 7 days ((15.09±1.75) g, (10.33±0.73) g) and 14 days ((15.07±1.49) g, (9.87±0.98) g) after surgery (all P<0.01). (2)The difference of the intensity of MBP in the ipsilateral Ⅰ-Ⅲ laminae of spinal dorsal horn staining was significant among 4 groups ( F=92.06, P<0.001). Compared with sham group, the intensity of MBP staining in the ipsilateral Ⅰ-Ⅲ laminae of spinal dorsal horn in pain model group was significantly decreased ((13.26±1.90)%, (36.37±0.68)%) ( P<0.01) ). Compared with pain model group, the intensity of MBP staining in the ipsilateral Ⅰ-Ⅲ laminae of spinal dorsal horn in electroacupuncture group ((28.21±3.15)%) was significantly increased after electroacupuncture treatment ( P<0.01). (3) The differences of the expressions of BACE1, NRG1 Ⅲ and p-ErbB2 in the ipsilateral Ⅰ-Ⅲ laminae of spinal dorsal horn were significant among the 4 groups ( F=31.04, 21.20, 11.74, all P<0.01). Compared with sham group, the expressions of BACE1, NRG1 Ⅲ and p-ErbB2 in the ipsilateral Ⅰ-Ⅲ laminae of spinal dorsal horn in pain model group were significantly downregulated (BACE1 (0.42±0.09), (1.16±0.13); NRG1 Ⅲ (0.54±0.05), (1.00±0.10); p-ErbB2 (0.73±0.06), (1.02±0.15) ) (all P<0.05). Compared with pain model group, the expression of BACE1 (0.86±0.09), NRG1 Ⅲ (0.81±0.05) and p-ErbB2 (1.12±0.04) in the ipsilateral Ⅰ-Ⅲ laminae of spinal dorsal horn in electroacupuncture group were upregulated(all P<0.05). Conclusion:Electroacupuncture treatment could relieve neuropathic pain, improve the demyelination and upregulate the expressions of myelin-related proteins in the ipsilateral Ⅰ-Ⅲ laminae of spinal dorsal horn.

Rosuvastatin(RVS)is an excellent drug with anti-inflammatory and lipid-lowering properties in the aca-demic and medical fields.However,this drug faces a series of challenges when used to treat atherosclerosis caused by hyperhomocysteinemia(HHcy),including high oral dosage,poor targeting,and long-term toxic side effects.In this study,we applied nanotechnology to construct a biomimetic nano-delivery system,macrophage membrane(M?m)-coated RVS-loaded Prussian blue(PB)nanoparticles(MPR NPs),for improving the bioavailability and targeting capacity of RVS,specifically to the plaque lesions associated with HHcy-induced atherosclerosis.In vitro assays demonstrated that MPR NPs effectively inhibited the Toll-like receptor 4(TLR4)/hypoxia-inducible factor-1α(HIF-1α)/nucleotide-binding and oligomerization domain(NOD)-like receptor thermal protein domain associated protein 3(NLRP3)signaling pathways,reducing pyroptosis and inflammatory response in macrophages.Additionally,MPR NPs reversed the abnormal distribution of adenosine triphosphate(ATP)-binding cassette transporter A1(ABCA1)/ATP binding cassette transporter G1(ABCA1)/ATP binding cassette transporter G1(ABCG1)caused by HIF-1α,promoting cholesterol efflux and reducing lipid deposition.In vivo studies using apolipoprotein E knockout(ApoE-/-)mice confirmed the strong efficacy of MPR NPs in treating atherosclerosis with favorable bio-security,and the mechanism behind this efficacy is believed to involve the regulation of serum metabolism and the remodeling of gut microbes.These findings suggest that the synthesis of MPR NPs provides a promising nanosystem for the targeted therapy of HHcy-induced atherosclerosis.

Objective To investigate the difference of CT features of gastrointestinal stromal tumors(GIST),neurogenic tumors,and leiomyomas in stomach.Methods A retrospective analysis was performed on clinical and CT features from 312 cases of GIST,21 cases of neurogenic tumors,and 35 cases of leiomyomas in stomach.Results GIST were most commonly found in the body of stomach and exhibited large tumor sizes and late onset.CT showed GIST predominantly showed intraluminal and mixed growth pattern with irregular or round shapes and uneven density,and cystic degeneration and calcification were frequently observed.The CT values of GIST in the arterial phase and the degree of arterial enhancement were higher,with light to moderate arterial phase enhancement and moderate to marked venous phase enhancement.Gastric leiomyomas had smaller tumor sizes and presented mainly in the cardia,gastric fundus,and lesser curvature of gastric body.CT showed the intraluminal growth pattern,primarily in round shapes with uniform density,lower incidence of cystic degeneration and calcification,both the arterial and venous phase CT values and the extent of enhancement in these phases were lower,showed no or slight enhancement during the arterial phase and light to moderate enhancement during the venous phase.Gastric neurogenic tumors were predominantly located in the gastric body and antrum.CT showed the tumors demonstrated extraluminal and mixed growth patterns,most with oval-shaped appearace,uniform density and the venous phase CT values and the degree of enhancement were higher,with light to moderate arterial enhancement and moderate to marked venous enhancement.Conclusion GIST,neurogenic tumors,and leiomyomas in stomach can be differentiated based on their distinct CT features.Accurate recognition of these features aids in the differential diagnosis of these kinds of tumors.

Objective The oxidative damage of DNA can be caused by excessive levels of Reactive oxygen species(ROS).Monitoring of DNA oxidative damage enables effective evaluation of ROS damage effects.Although the detection of DNA damage effects based on microbial sensor allows quantitative analysis of oxidative damage,the ROS clearance mechanism existed in bacterial will affect the sensitive of detection.The work of this article is to knockout the key genes of ROS clearance mechanism and construct an antioxidant gene-knock-out microbial sensor.The microbial sensor can realize sensitive monitoring of DNA damage effects and then evaluates the damage effects of cells by ROS.Methods The antioxidant damage genes of bacterial ahpCF,katE and katG were knocked out by λ-Red homologous recombination and antioxidant gene-knockout microbial sensor was constructed.The nalidixic acid sodium salt and UV irradiation were used to characterize the performance for monitoring of DNA damage effects.Results The antioxidant gene-knockout microbial sensors ΔahpC,ΔahpCF/ΔkatEG and ΔahpCF/ΔkatE/ΔkatG were constructed successfully.The results showed that the microbial sensor ΔahpCF/ΔkatE/ΔkatGl had the highest sensitive of damage effects and the limit of detection for nalidixic acid sodium salt was 0.40 μmol/L.In addition,1.80 min of UV irradiation(254 nm)was sufficient to induce a significant fluorescent expression effect in the engineered bacteria.Conclusion In this article,antioxidant gene-knockout microbial sensors had been constructed to realize active and sensitive monitoring of DNA damage effects such as DNA damage reagents and UV irradiation.The sensors could provide an active,effective,and sensitive potential monitoring method for future evaluation of radiation effects in space.

Objective: To investigate the clinical characteristics and maternal and fetal prognosis of pregnant women with acute fatty liver of pregnancy (AFLP). Methods: The clinical data of 86 AFLP pregnant women admitted to the Third Affiliated Hospital of Guangzhou Medical University from September 2017 to August 2022 were collected, and their general data, clinical characteristics, laboratory tests and maternal and fetal outcomes were retrospectively analyzed. Results: (1) General information: the age of the 86 pregnant women with AFLP was (30.8±5.4) years, and the body mass index was (21.0±2.5) kg/m². There were 50 primiparas (58.1%, 50/86) and 36 multiparas (41.9%, 36/86). There were 64 singleton pregnancies (74.4%, 64/86) and 22 twin pregnancies (25.6%, 22/86). (2) Clinical characteristics: the main complaints of AFLP pregnant women were gastrointestinal symptoms, including epigastric pain (68.6%, 59/86), nausea (47.7%, 41/86), anorexia (46.5%, 40/86), vomiting (39.5%, 34/86). The main non-gastrointestinal symptoms were jaundice of skin and/or scleral (54.7%, 47/86), edema (38.4%, 33/86), fatigue (19.8%, 17/86), bleeding tendency (16.3%, 14/86), polydipsia or polyuria (14.0%, 12/86), skin itching (8.1%, 7/86), and 17.4% (15/86) AFLP pregnant women had no obvious symptoms. (3) Laboratory tests: the incidence of liver and kidney dysfunction and abnormal coagulation function in AFLP pregnant women was high, and the levels of blood ammonia, lactate dehydrogenase and lactic acid were increased, and the levels of hemoglobin, platelet and albumin decreased. However, only 24 cases (27.9%, 24/86) of AFLP pregnant women showed fatty liver by imageology examination. (4) Pregnancy outcomes: ① AFLP pregnant women had a high incidence of pregnancy complications, mainly including renal insufficiency (95.3%, 82/86), preterm birth (46.5%, 40/86), hypertensive disorders in pregnancy (30.2%, 26/86), gestational diabetes mellitus (36.0%, 31/86), fetal distress (24.4%, 21/86), pulmonary infection (23.3%, 20/86), disseminated intravascular coagulation (16.3%, 14/86), multiple organ dysfunction syndrome (16.3%, 14/86), hepatic encephalopathy (9.3%, 8/86), and intrauterine fetal death (2.3%, 2/86). ② Treatment and outcome of AFLP pregnant women: the intensive care unit transfer rate of AFLP pregnant women was 66.3% (57/86). 82 cases were improved and discharged after treatment, 2 cases were transferred to other hospitals for follow-up treatment, and 2 cases (2.3%, 2/86) died. ③ Neonatal outcomes: except for 2 cases of intrauterine death, a total of 106 neonates were delivered, including 39 cases (36.8%, 39/106) of neonatal asphyxia, 63 cases (59.4%, 63/106) of neonatal intensive care unit admission, and 3 cases (2.8%, 3/106) of neonatal death. Conclusions: AFLP is a severe obstetric complication, which is harmful to mother and fetus. In the process of clinical diagnosis and treatment, attention should be paid to the clinical manifestations and laboratory tests of pregnant women, early diagnosis and active treatment, so as to improve maternal and fetal outcomes.
Pregnancy ; Infant, Newborn ; Female ; Humans ; Adult ; Retrospective Studies ; Premature Birth/epidemiology* ; Pregnancy Complications/diagnosis* ; Fatty Liver/diagnosis* ; Fetal Death ; Stillbirth

Objective:To assess the predictive performance of the risk of cardiovascular diseases (CVD) derived from the China Kadoorie Biobank (CKB-CVD) model, prediction for atherosclerotic cardiovascular disease (ASCVD) risk in China (China-PAR) model, and the risk of fatal and nonfatal ischemic cardiovascular diseases derived from the USA-People′s Republic of China Collaborative Study (USA-PRC) model in Chinese Multi-provincial Cohort Study (CMCS).Methods:In this prospective cohort study, a total of 21 948 individuals aged ≥35 years without CVD were selected from 8 provinces and cities in China during the CMCS survey from 1992 to 2005 for 10-year follow-up. The occurrence of CVD or ASCVD events during the follow-up period was used as the gold standard. The CKB-CVD and China-PAR models were used to calculate the predicted risk of CVD events, while the USA-PRC model was used to calculate the predicted risk of ASCVD events. The discrimination of the models was evaluated using the C-statistic, and the calibration was assessed using the Hosmer-Lemeshow χ2 test and decile plot. Results:During the 10-year follow-up, a total of 955 (4.4%) CVD events, including 791 (3.6%) ASCVD events, were recorded among the study participants. The C-index for the CKB-CVD, China-PAR, and USA-PRC models were 0.775 (95% CI: 0.757-0.793), 0.781 (95% CI: 0.763-0.798), and 0.769 (95% CI: 0.750-0.789) for men, and 0.762 (95% CI: 0.737-0.788), 0.769 (95% CI: 0.745-0.794), and 0.767 (95% CI: 0.741-0.794) for women, respectively. China-PAR model showed good calibration for men ( χ2=2.20), however, both CKB-CVD and USA-PRC models demonstrated poor calibration in both men and women ( χ2>20). The results indicated that the CKB-CVD model overestimated the risk of CVD events in both males and females, while the China-PAR model underestimated the risk in females. Furthermore, the USA-PRC model underestimated the risk of ASCVD in both males and females in most decile groups, but overestimated the risk in the highest decile group. Conclusion:The CKB-CVD, China-PAR, and USA-PRC risk assessment models show some degree of deviation from the actual risk of events in the CMCS cohort, but all exhibit good discrimination.

Objective:To explore the risk factors of pinhole infection in patients with external fixators, and build a risk prediction model.Methods:From January 2018 to June 2019, the data of patients ( n=300) with external fixators in the Department of Trauma and Orthopedics, South Hospital, South Medical University, were selected by retrospective survey, and were divided into infection group and non-infection group according to whether pinhole infection occurred in the postoperative case records. Single factor analysis and Logistic regression analysis were used to establish the risk factors of pinhole infection and its prediction model. The grade of risk prediction was constructed by the assignment method. Results:Among 300 patients with external fixators, 103 (34.33%) had pinhole infection and 197 (65.67%) had no infection. Logistic regression analysis showed that basic disease [ OR=4.726 (one of diabetes, pulmonary infection), 17.053 (two of diabetes, pulmonary infection, cardiovascular diseases) ], postoperative albumin [ OR=0.082 (<25 g/L) ], postoperative hemoglobin [ OR=3.715 (>90-120 g/L), 9.720 (>60-90 g/L), 7.338 (30~60 g/L) ], intraoperative bleeding volume [ OR=2.196 (200-400 ml), OR=3.256 (>400 ml) ] and the type of disinfectant [ OR=3.897 (chlorhexidine), 3.625 (iodophor + chlorhexidine) ] were risk factors for pinhole infection in patients with external fixators ( P<0.05). The constructed model was divided into high-risk group (≥ 7 points), higher-risk group (5-6 points), medium-risk group (4 points), low-risk group (3 points) and lower-risk group (0-2 points) . Conclusions:The model can well predict the risk of pinhole infection of orthopedic external fixator, provide reference for medical and nursing staff to identify the risk of external fixation infection in time, and prevent the occurrence of infection as soon as possible.