ObjectiveTo investigate the effects of jatrorrhizine on endogenous metabolites and metabolic pathways in the mouse model of ulcerative colitis. MethodsThirty male C57BL/6J mice were randomly divided into the normal group， the model group， the low-dose and high-dose jatrorrhizine groups （0.04， 0.16 g·kg^-1）， and the mesalazine group （0.52 g·kg^-1）The mouse model of ulcerative colitis was established with 3% dextran sulfate sodium （DSS） and treated with different doses of jatrorrhizine by gavage. The changes in body weight， colon length， disease activity index （DAI）， and colonic histopathology were analyzed to evaluate the therapeutic effects of jatrorrhizine. UPLC-Q-TOF/MS was employed to determine the serum and fecal levels of metabolites in mice. Metabolomics methods were used to screen the differential metabolites， on the basis of which the potential therapeutic mechanism of jatrorrhizine on DSS-induced ulcerative colitis in mice was investigated. ResultsAfter intervention with jatrorrhizine， the model mice showed significantly decreased DAI（P<0.05，P<0.01）， recovered colon length，（P<0.05，P<0.01） and alleviated histopathology of the colon. The metabolomics study screened out 13 differential metabolites in the serum and 8 differential metabolites in the feces. The pathway enrichment analysis predicted three potential metabolic pathways： Biosynthesis of unsaturated fatty acids， phenylalanine， tyrosine and tryptophan biosynthesis， and phenylalanine metabolism. ConclusionJatrorrhizine may treat ulcerative colitis by regulating the biosynthesis and metabolism of amino acids and the synthesis of unsaturated fatty acids.

Objective: To determine the association between exposure to entertainment screen content on mobile phones and symptoms of anxiety-depression co-morbidity among college students,so as to provide evidence for mental health interventions. Methods: A baseline survey was conducted from April to May 2019. A total of 1 135 college students were selected from one university each in Shangrao City, Jiangxi Province and Hefei City, Anhui Province using cluster random sampling method. A follow up study was conducted in November 2019, resulting in 1 110 matched valid responses. Self rating questionnaires were used to assess the exposure of entertainment screen content. The Depression Anxiety Stress Scale-21(DASS-21) and the Patient Health Questionnaire-9 (PHQ-9) were used to evaluate the anxiety symptoms, depressive symptoms, and symptoms of anxiety-depression co-morbidity among college students. A multivariate binary Logistic regression model was constructed following initial intergroup comparisons with Chi-square test to determine the association between baseline exposure to mobile entertainment screen content and the risk of symptoms of anxiety depression co-morbidity at baseline and the 6 month follow up. Results: The prevalence rates of symptoms of anxiety-depression co-morbidity among college students were 25.4% and 20.6% at baseline and follow up, respectively.After adjusting for confounding factors such as gender, self rated family economic status and self rated health status, the results of multivariate binary Logistic regression analysis showed that compared with the appropriate exposure level group, the exposure of entertainment screen content on mobile phones at baseline, including frequent exposure to reading( OR =1.65,95% CI =1.14-2.39), occasional exposure to other entertainment screen content ( OR =1.46,95% CI =1.01-2.10)and frequent exposure to other entertainment screen content( OR =1.76,95% CI =1.20-2.60), increased the co-occurrence risk of symptoms of anxiety-depression co-morbidity among college students during the follow up period (all P <0.05). Conclusion Occasional or frequert exposure to mobile entertainment screen content can increase the risk of symptoms of anxiety depression co-morbidity among college students.

OBJECTIVE To investigate the effect and mechanism of modified Lichong decoction （MLCD） on the apoptosis of transplanted tumor cells in nude mice. METHODS Human gastric cancer AGS cells were cultured， and a nude mice transplanted tumor model was established. The nude mice were divided into the model group and MLCD low-， medium- and high-dose groups （150， 300， 600 mg/kg）. They were given distilled water or the corresponding drug solution by gavage once daily for four consecutive weeks. The size of transplanted tumors in nude mice was measured every six days， and the tumor volume was calculated. After the medication， the nude mice were sacrificed， and the transplanted tumor tissues were isolated. The contents of lactate dehydrogenase （LDH） and reactive oxygen species （ROS） in the transplanted tumor tissues were detected， and the changes in mitochondrial membrane potential were assessed. The pathological morphological changes were observed. The enzymatic activities of caspase-3， caspase-8， and caspase-9， as well as protein expressions of Fas and FasL and mRNA expressions of caspase-3， caspase-8， caspase-9， Fas and FasL in the transplanted tumor tissues， were detected. RESULTS Compared with the model group， the volume of transplanted tumors in nude mice from all MLCD dose groups was reduced to varying degrees. The contents of LDH and ROS， as well as the enzymatic activities of caspase-3， caspase-8 and caspase-9， were significantly increased/enhanced. The mitochondrial membrane potential was significantly decreased. The protein expressions of Fas and FasL， and the mRNA expressions of caspase-3， caspase-8， caspase-9， Fas and FasL were significantly up-regulated. Most of these differences were statistically significant （ P ＜0.05 or P ＜0.01）. Pathological results showed that with increasing doses of MLCD， the cellular density in the transplanted tumor tissues gradually decreased， and typical morphological features of apoptosis， such as loosening and increasing fragmentation， became more prominent. CONCLUSIONS MLCD can induce apoptosis in transplanted tumor cells of nude mice， and its mechanism may be related to the activation of the Fas/FasL pathway and the caspase apoptotic pathway.

Objective: To analyze the association and dose response relationship between physical activity and inflammatory markers in college students, so as to provide a reference for promoting cardiometabolic health in college students. Methods: A cluster random sampling method was used to select 747 college students from two universities in Hefei, Anhui Province and Shangrao, Jiangxi Province from April to May 2019. Physical activity was assessed by using the International Physical Activity Questionnaire-Short Form (IPAQ-SF), and peripheral blood was collected to detect plasma inflammatory factor levels [including hypersensitive C reactive protein (hsCRP), interleukin-10 (IL-10), interleukin-1β (IL-1β), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α)]. The differences between the groups were compared by using the χ 2 test and the Kruskal-Wallis rank sum test, and the association between physical activity and inflammatory markers was analyzed by using the Generalized Linear Model. The dose response relationship between physical activity and inflammatory markers was analyzed using the Restricted Cubic Spline Model. Results: The proportions of low physical activity, moderate physical activity, and high physical activity groups of college students were 15.9%, 53.7% and 30.4%, respectively. The levels of hsCRP, IL-10, IL-1β, IL-6 and TNF-α in the high physical activity group were 0.38(0.21, 1.10)mg/L, 70.74(47.90, 116.43)pg/mL, 1.75(1.21, 2.64)pg/mL, 4.33(2.93, 6.82) pg/mL , 5.27(3.89, 7.30)pg/mL,the levels in the low physical activity group were 0.80(0.31, 1.30)mg/L, 73.88 (47.90, 124.24)pg/mL, 1.88(1.42, 2.81) pg/mL, 4.82 (3.64, 6.67) pg/mL, 5.63 (4.34, 7.62)pg/mL, the levels in the moderate physical activity group were 0.63(0.25, 1.30)mg/L, 89.78(58.21, 127.65)pg/mL, 2.21(1.59, 3.27)pg/mL, 5.15( 3.72 , 7.72)pg/mL, 5.87( 4.63 , 8.00)g/mL, and the differences were statistically significant ( H=10.66, 11.38, 27.79, 14.13, 9.44, P <0.05). After adjusting for variables such as gender, body mass index, smoking, alcohol consumption and health status, the results of Generalized Linear Model showed that compared with the high physical activity group, the low physical activity group ( OR=2.20, 95%CI = 1.46- 3.31) and the moderate physical activity group ( OR=1.65, 95%CI =1.22-2.25) were more likely to have high levels of hsCRP, and the moderate physical activity group was more likely to have high levels of IL-1β ( OR=1.85, 95%CI =1.36-2.51), IL-6 ( OR=1.44, 95%CI =1.06-1.96), and TNF-α ( OR=1.43, 95%CI =1.05-1.94) ( P <0.05). The Restricted Cubic Spline Model showed that there was no linear dose response relationship between the time of moderate to vigorous physical activity weekly and IL-10, IL-6, II-1β, and TNF-α ( P <0.05). Conclusion There is an association between physical activity and inflammation in college students, and moderate to high intensity per week could reduce inflammation levels to promote cardiometabolic health in college students.

ObjectiveTo investigate the main risk factors for liver cirrhosis in chronic hepatitis B （CHB） patients with high metabolic risk， to establish a noninvasive predictive model， and to compare the diagnostic efficiency of this model and other models including fibrosis-4 （FIB-4）， aspartate aminotransferase-to-platelet ratio index （APRI）， gamma-glutamyl transpeptidase-to-platelet ratio （GPR）， and Forns index. MethodsA total of 527 CHB patients with high metabolic risks who were admitted to The Second Affiliated Hospital of Guangxi Medical University from September 1， 2017 to October 31， 2022 were enrolled as subjects， and they were randomly divided into modeling group with 368 patients and validation group with 159 patients at a ratio of 7∶3. The LASSO regression analysis and the multivariate Logistic regression analysis were performed for the modeling group to identify independent risk factors， and a nomogram model was established. The receiver operating characteristic （ROC） curve， the calibration curve， and the decision curve analysis were used to validate the nomogram prediction model in the modeling group and the validation group and assess its discriminatory ability， calibration， and clinical practicability. The Delong test was used to compare the area under the ROC curve （AUC） of the nomogram prediction model and other models. ResultsThe multivariate Logistic regression analysis showed that prealbumin （odds ratio ［OR］ = 0.993， 95% confidence interval ［CI］： 0.988 — 0.999， P= 0.019）， thrombin time （OR=1.182， 95% CI： 1.006 — 1.385， P=0.047）， log₁₀ total bilirubin （TBil） （OR=1.710， 95%CI： 1.239 — 2.419， P=0.001）， and log₁₀ alpha-fetoprotein （AFP） （OR=1.327， 95%CI： 1.052 — 1.683， P=0.018） were independent influencing factors for liver cirrhosis in CHB patients with high metabolic risks. A nomogram model for risk prediction was established based on the multivariate analysis， which had an AUC of 0.837 （95%CI： 0.788 — 0.888）， a specificity of 73.5%， and a sensitivity of 84.7%， as well as a significantly higher diagnostic efficiency than the models of FIB-4 （0.739）， APRI （0.802）， GPR （0.800）， and Forns index （0.709） （Z=2.815， 2.271， 1.989， and 2.722， P=0.005， 0.017， 0.045， and 0.006）. ConclusionThe nomogram model established based on prealbumin， thrombin time， log₁₀ TBil， and log₁₀ AFP has a certain clinical application value.

Objective To compare the postoperative enhanced recovery outcomes of lobectomy performed under non-intubated video-assisted thoracic surgery (NIVATS) versus intubated video-assisted thoracic surgery (IVATS). Methods Computerized searches were performed in the following databases: China National Knowledge Infrastructure (CNKI), Wanfang Data, VIP Information, China Biomedical Literature Database (CBMdisc), Web of Science, Clinicaltrials.gov, The Cochrane Library, EMbase, and PubMed. We collected randomized controlled trials (RCTs) and observational studies comparing NIVATS and IVATS. The search period extended from the inception of each database to April 1, 2023. Two independent researchers screened the literature and assessed study quality. Results A total of 14 studies were included, comprising 4 RCTs, 7 retrospective cohort studies, and 3 propensity score matching studies, involving 1 840 patients. Meta-analysis results indicated that, compared to IVATS, NIVATS was associated with significantly shorter operative time [MD=–13.39, 95%CI (–20.16, –6.62), P<0.001], shorter length of hospital stay [MD=–0.81, 95%CI (–1.39, –0.22), P=0.005], shorter chest tube duration [MD=–0.73, 95%CI (–1.36, –0.10), P=0.02], shorter postoperative anesthesia recovery time [MD=–20.34, 95%CI (–26.83, –13.84), P<0.001], and shorter time to oral intake after surgery [MD=–5.68, 95%CI (–7.63, –3.73), P<0.001]. Furthermore, NIVATS showed a lower incidence of postoperative airway complications [OR=0.49, 95%CI (0.34, 0.71), P<0.001] and less total chest tube drainage volume [MD=–251.11, 95%CI (–398.25, –103.98), P<0.001], all contributing to significantly accelerated postoperative enhanced recovery for patients. Conclusion NIVATS is a safe and technically feasible anesthesia method in thoracoscopic lobectomy, which can to some extent replace IVATS.

OBJECTIVE: To observe the effect of transcutaneous electrical acupoint stimulation (TEAS) on postoperative pain in patients undergoing modified radical mastectomy for breast cancer. METHODS: A total of 140 female patients scheduled for unilateral modified radical mastectomy for breast cancer undergoing general anesthesia were randomized into a TEAS group (70 cases) and a sham TEAS group (70 cases, 2 cases dropped out). Patients in both groups received TEAS or sham TEAS at bilateral Neiguan (PC6), Zusanli (ST36), and Danzhong (CV17), respectively, from 30 min before anesthesia induction until the end of surgery, and on 1st, 2nd, and 3rd days after surgery for 30 min a time, once a day. On 1st, 2nd, and 3rd days after surgery, the pain visual analogue scale (VAS) score was observed; on 3, 6, 12 months after surgery, the incidence rate of chronic pain was observed; before surgery, and on 1st, 3rd, and 7th days after surgery, the serum levels of tumor necrosis factor (TNF)-α, interleukin (IL)-6 and IL-10 were detected; the number of analgesia pump press, rescue analgesia, and the occurrence of adverse reaction after surgery were recorded in the two groups. RESULTS: In the TEAS group, the VAS scores on 1st and 2nd days after surgery, and the incidence rates of chronic pain on 3 and 6 months after surgery were lower than those in the sham TEAS group (P<0.05). On 1st, 3rd, and 7th days after surgery, the serum levels of TNF-α, IL-6, and IL-10 were increased compared with those before surgery in both groups (P<0.05, P<0.01); the above indexes in the TEAS group were lower than those in the sham TEAS group (P<0.05). The number of analgesia pump press and the incidence rate of rescue analgesia after surgery in the TEAS group were lower than those in the sham TEAS group (P<0.05). There was no statistically significant difference in the incidence of adverse reactions after surgery between the two groups (P>0.05). CONCLUSION TEAS can effectively improve both the postoperative acute pain and chronic pain in patients undergoing modified radical mastectomy for breast cancer, the mechanism may relate to inhibiting the inflammatory reaction.
Humans ; Female ; Acupuncture Points ; Pain, Postoperative/blood* ; Middle Aged ; Breast Neoplasms/surgery* ; Adult ; Transcutaneous Electric Nerve Stimulation ; Mastectomy, Modified Radical/adverse effects* ; Interleukin-6/blood* ; Tumor Necrosis Factor-alpha/blood* ; Interleukin-10/blood* ; Aged

Cholangiocarcinoma (CCA) is a fatal malignancy with steadily increasing incidence and poor prognosis. Since most CCA cases are diagnosed at an advanced stage, systemic therapies, including chemotherapy, radiotherapy, targeted therapy, and immunotherapy, play a crucial role in the management of unresectable CCA. The recent advances in targeted therapies and immunotherapies brought more options in the clinical management of unresectable CCA. This review depicts the advances of targeted therapies and immunotherapies for unresectable CCA, summarizes crucial clinical trials, and describes the efficacy and safety of different drugs, which may help further develop precision and individualization in the clinical treatment of unresectable CCA.
Humans ; Cholangiocarcinoma/drug therapy* ; Immunotherapy/methods* ; Bile Duct Neoplasms/drug therapy* ; Molecular Targeted Therapy/methods*

Alzheimer's disease (AD) is the major form of dementia in the elderly and is closely related to the toxic effects of microglia sustained activation. In AD, sustained microglial activation triggers impaired synaptic pruning, neuroinflammation, neurotoxicity, and cognitive deficits. Accumulating evidence has demonstrated that aberrant expression of deubiquitinating enzymes is associated with regulating microglia function. Here, we use RNA sequencing to identify a deubiquitinase YOD1 as a regulator of microglial function and AD pathology. Further study showed that YOD1 knockout significantly improved the migration, phagocytosis, and inflammatory response of microglia, thereby improving the cognitive impairment of AD model mice. Through LC-MS/MS analysis combined with Co-IP, we found that Myosin heavy chain 9 (MYH9), a key regulator maintaining microglia homeostasis, is an interacting protein of YOD1. Mechanistically, YOD1 binds to MYH9 and maintains its stability by removing the K48 ubiquitin chain from MYH9, thereby mediating the microglia polarization signaling pathway to mediate microglia homeostasis. Taken together, our study reveals a specific role of microglial YOD1 in mediating microglia homeostasis and AD pathology, which provides a potential strategy for targeting microglia to treat AD.

Gelsemium elegans (G. elegans) is an extremely poisonous plant that is widely distributed in southern China and southeastern Asia. G. elegans poisoning events occur frequently in southern China, and are therefore an urgent public health problem requiring multidisciplinary action. However, the toxic components and toxicological mechanisms remain unclear. Here, we describe a systematic investigation on the toxic components of G. elegans, resulting in the isolation and identification of 120 alkaloids. Based on acute toxicity screening, the structure-toxicity relationship of Gelsemium alkaloids was proposed for the first time. Moreover, gelsedine- and humantenine-type alkaloids were detected in the clinical blood sample, and were confirmed to be causative in the poisoning. The most toxic compound, gelsenicine (1), had selective inhibitory effects toward ventral respiratory group (VRG) neurons in the medulla, which is the main brain region controlling respiration in the central nervous system. Gelsenicine (1) strongly inhibited the firing of action potentials in VRG neurons through its ability to stimulate GABA_A receptors, the main receptors involved in inhibitory neurotransmission. Application of GABA_A receptor antagonists successively reversed action potential firing in gelsenicine (1)-treated VRG neurons. Importantly, the GABA_A receptor antagonists securinine and flumazenil significantly increased the survival of poisoned animals. Our findings provide insight into the components and mechanisms of G. elegans toxicity, and should assist the development of effective emergency treatments for G. elegans poisoning.