Lipotoxicity is a pivotal factor that initiates and exacerbates liver injury and is involved in the development of metabolic-associated fatty liver disease (MAFLD). However, there are few reported lipotoxicity inhibitors. Here, we identified a natural anti-lipotoxicity candidate, HN-001, from the marine fungus Aspergillus sp. C1. HN-001 dose- and time- dependently reversed palmitic acid (PA)-induced hepatocyte death. This protection was associated with IRE-1α-mediated XBP-1 splicing inhibition, which resulted in suppression of XBP-1s nuclear translocation and transcriptional regulation. Knockdown of XBP-1s attenuated lipotoxicity, but no additional ameliorative effect of HN-001 on lipotoxicity was observed in XBP-1s knockdown hepatocytes. Notably, the ER stress and lipotoxicity amelioration was associated with PLA2. Both HN-001 and the PLA2 inhibitor MAFP inhibited PLA2 activity, reduced lysophosphatidylcholine (LPC) level, subsequently ameliorated lipotoxicity. In contrast, overexpression of PLA2 caused exacerbation of lipotoxicity and weakened the anti-lipotoxic effects of HN-001. Additionally, HN-001 treatment suppressed the downstream pro-apoptotic JNK pathway. In vivo, chronic administration of HN-001 (i.p.) in mice alleviated all manifestations of MAFLD, including hepatic steatosis, liver injury, inflammation, and fibrogenesis. These effects were correlated with PLA2/IRE-1α/XBP-1s axis and JNK signaling suppression. These data indicate that HN-001 has therapeutic potential for MAFLD because it suppresses lipotoxicity, and provide a natural structural basis for developing anti-MAFLD candidates.

Objective To make an epidemiological investigation on traditional Chinese medicine(TCM)dampness syndrome manifestations in the population at risk of cerebrovascular diseases in Guangdong area.Methods A cross-sectional study was conducted to analyze the clinical data related to the risk of cerebrovascular diseases in 330 Guangdong permanent residents.The diagnosis of dampness syndrome,quantitative scoring of dampness syndrome and rating of the risk of stroke were performed for the investigation of the distribution pattern of dampness syndrome and its influencing factors.Results(1)A total of 306(92.73%)study subjects were diagnosed as dampness syndrome.The percentage of dampness syndrome in the risk group was 93.82%(258/275),which was slightly higher than that of the healthy group(48/55,87.27%),but the difference was not statistically significant(χ2 = 2.91,P = 0.112).The quantitative score of dampness syndrome in the risk group was higher than that of the healthy group,and the difference was statistically significance(Z =-2.24,P = 0.025).(2)Among the study subjects at risk of cerebrovascular disease,evaluation time(χ2 = 26.11,P = 0.001),stroke risk grading(χ2= 8.85,P = 0.031),and history of stroke or transient ischemic attack(TIA)(χ2 = 9.28,P = 0.015)were the factors influencing the grading of dampness syndrome in the population at risk of cerebrovascular disease.Conclusion Dampness syndrome is the common TCM syndrome in the population of Guangdong area.The manifestations of dampness syndrome are more obvious in the population with risk factors of cerebrovascular disease,especially in the population at high risk of stroke,and in the population with a history of stroke or TIA.The assessment and intervention of dampness syndrome should be taken into account for future project of stroke prevention in Guangdong.

Cryoablation therapy with explicit anti-tumor mechanisms and histopathological manifestations has a long history.A large number of clinical practice has shown that cryoablation therapy is safe and effective,making it an ideal tumor treatment method in theory.Previously,its efficacy and clinical application were constrained by the limitations of refrigerants and refrigeration equipment.With the development of the new generation of cryoablation equipment represented by argon helium knives,significant progress has been made in refrigeration efficien-cy,ablation range,and precise temperature measurement,greatly promoting the progression of tumor cryoablation technology.This consensus systematically summarizes the mechanism of cryoablation technology,indications for oral mucosal melanoma(OMM)cryotherapy,clinical treatment process,adverse reactions and management,cryotherapy combination therapy,etc.,aiming to provide reference for carrying out the standardized cryoablation therapy of OMM.

Objective:To effectively quantify and evaluate the quality of different deformation registration algorithms, in order to enhance the possibility of implementing deformation registration in clinical practice.Methods:The Jacobian determinant mean (JDM) is proposed based on the Jacobian determinant (JD) of displacement vector field (DVF), and the Jacobian determinant error (DJDE) is introduced by incorporating the JD of the inverse DVF. The optical flow method (OF-DIR) and fast demons method with elastic regularization (FD-DIR) were tested on nasopharyngeal and lung cancer datasets. Finally, JDM and DJDE with the Jacobian determinant negative percentage (JDNP), inverse consistency error (ICE) and normalized mean square error (NMSE) were used to evaluate the registration algorithms and compare the differences evaluation indicators in different tumor images and different algorithms, and the receiver operating curve (ROC) was analyzed in evaluation.Results:In lung cancer, OF-DIR outperformed FD-DIR in terms of JDM, NMSE, DJDE and ICE, and the difference was statistically significant( z = -2.24, -4.84, t = 4.01, 6.54, P<0.05). In nasopharyngeal carcinoma, DJDE, ICE and NMSE of OF-DIR were superior to FD-DIR, and the difference was statistically significant ( t = 4.46, -7.49, z = -2.22, P<0.05), but there was no significant difference in JDM ( P>0.05). In lung cancer and nasopharyngeal carcinoma, JDNP of OF-DIR was worse than that of FD-DIR, and the difference was statistically significant ( z = -4.29, -4.02, P<0.01). In addition, DJDE is more specific and sensitive on ROC curve (AUC=0.77), and has different performance result for tumor images at different sites. Conclusions:The JDM and DJDE evaluation metrics proposed are effective for deformation registration algorithms. OF-DIR is suitable for both lung cancer and nasopharyngeal carcinoma, while the influence of organ motion on the registration effect should be considered when using FD-DIR.

Objective:To investigate the necessity of adaptive re-planning during radiotherapy for nasopharyngeal carcinoma (NPC) and its impact on dose improvement.Methods:Clinical data of 89 NPC patients admitted to Sun Yat-sen University Cancer Center from July 2014 to December 2017 were retrospectively analyzed. All patients received 25+7 rounds of adaptive re-planning during radiotherapy. Plan-A was defined as the initial CT scan-based 25-fraction radiotherapy plan, while plan-B was defined as the re-planned 7-fraction radiotherapy plan based on a subsequent CT scan. The changes in the target and parotid gland volumes were compared between plan-A and plan-B. Plan-I was a one-time simulation of plan-A extended to 32 fraction radiotherapy plan, and plan-II was generated through registration and fusion of the plan-A and plan-B for adaptive re-planning. The differences in dose metrics, homogeneity index (HI), conformity index (CI), and dose to organs at risk (OAR) were compared between plan-I and plan-II. Statistical analysis was performed by using paired t-test. Results:Compared with plan-A, the gross tumor volume of massive bleeding lesions (GTV nx) and parotid gland volume of plan-B were decreased by 13.14% and 11.12%, respectively (both P<0.001). While planning clinical target volume of metastatic lymph nodes (PCTV nd) of plan-B was increased by 7.75%( P<0.001). There were significant changes in the lymph nodes of plan-A and plan-B. The D mean, D 5%, D 95% of massive bleeding lesions planning target volume (PTV nx) and D 5% of high risk planning target volume (PTV1) in plan-II were all significantly higher than those in plan-I (all P<0.05). The CI of PTV nx and PTV1 in plan-II was closer to 1 than that in plan-I. In all assessed OAR, the D mean, D 50%, and D max of plan-II were significantly lower than those of plan-I (all P<0.05). Conclusions:During radiotherapy, NPC patients may experience varying degrees of primary tumor shrinkage, parotid gland atrophy, and lymph node changes. It is necessary to deliver re-planning and significantly improve the dose of target areas and OAR.

OBJECTIVE To observe the clinical efficacy of Huatan Tongluo Decoction in the treatment of post-stroke cognitive impairment(PSCI)with phlegm stasis obstructing collaterals syndrome,and its influence on the serum brain-derived neurotrophic fac-tor(BDNF)pathway-related factors.METHODS Sixty patients who met the inclusion criteria were collected and randomly divided into a control group and a treatment group with 30 patients each.The control group was given basic treatment and nimodipine,while the treatment group was given Huatan Tongluo Decoction on the basis of the treatment in the control group.The treatment course for both groups was 4 weeks.Changes in Mini-Mental State Examination(MMSE),TCM syndrome scores and serum levels of BDNF,nuclear transcription factor κB(NF-κB),B lymphocyte tumor-2(Bcl-2)and Bcl-2-associated X protein(Bax)were compared between the two groups before and after treatment.The TCM clinical efficacy in the two groups of patients was evaluated after treatment,and the oc-currence of adverse reactions was observed during treatment.RESULTS After treatment,the MMSE scores of the patients in the two groups increased significantly,the total TCM syndrome scores decreased significantly(P<0.01),and the treatment group was better than the control group(P<0.01);the serum BDNF,NF-κB,and Bcl-2 levels of the two groups of patients were significantly in-creased(P<0.05,P<0.01),and the Bax level was significantly decreased(P<0.01).The treatment group was better than the control group(P<0.01).CONCLUSION Huatan Tongluo Decoction can improve the clinical symptoms of PSCI patients with phlegm stasis obstructing collaterals,and is safe and effective.Its therapeutic mechanism may be related to regulating the BDNF pathway to protect nerve cells and inhibit nerve cell apoptosis.

Objective To investigate the difference of depressive symptoms between adolescents and adults,and to provide possible basis for early detection of adolescent depression.Methods From July 2021 to June 2022,a total of 4 096 patients with"depression"in the psychiatric clinic of the First Affiliated Hospital of Chongqing Medical University were selected as the research objects.They were divided into the adolescent group(n=2 439)and adult group(n=1 657)according to their ages,and the results of self-rating depression scale(SDS)and symptom checklist 90(SCL-90)were collected and analyzed.Results There were significant differences in nationality,residence,native place,family history and degree of depression between the two groups(P<0.05).The adolescent group has more severe depressive symptoms,which were mainly manifes-ted in negative ideas,obsessive-compulsive symptoms,hostile and interpersonal relationship,and psychotic symptoms(P<0.05).The adult group showed more obvious in sleep(P<0.05).Conclusion Early inter-vention should be carried out for adolescents'depressive symptoms such as negative thoughts.

Objective:To investigate the effects of using a high monounsaturated fatty acid (MUFA) and low carbohydrate formula on blood glucose levels and diarrhea treatment effects in critically ill neurological patients.Methods:A self-controlled before-and-after study design was employed, with 13 patients admitted to the neurology intensive care unit (ICU) of the First Affiliated Hospital of Sun Yat-sen University from November to December 2023, who were treated with a high MUFA and low carbohydrate formula [Glucerna enteral nutrition (EN) preparation]. Changes in blood glucose parameters within 7 days before and after the use of Glucerna EN preparation were analyzed, including standard deviation ( SD) of blood glucose, mean blood glucose (MG), median blood glucose, mean amplitude of glycemic excursions (MAGE), largest amplitude of glycemic excursions (LAGE), coefficient of variation ( CV) of blood glucose, the incidence of hyperglycemia (> 7.8 mmol/L) and severe hyperglycemia (> 13.9 mmol/L), and daily insulin dose. Changes in total protein (TP), albumin (ALB), hemoglobin (Hb), C-reactive protein (CRP), and white blood cell count (WBC) were observed before and after intervention. Improvement in diarrhea symptoms, Hart diarrhea score, Bristol Stool classification score, and incontinence dermatitis classification were also analyzed before and after the use of Glucerna EN preparation. Results:A total of 13 critically ill neurological patients were enrolled, among whom 9 patients had a history of hyperglycemia and 8 patients had diarrhea symptoms. After intervention with Glucerna, the patients' SD of blood glucose, MG, median blood glucose, MAGE, LAGE, CV of blood glucose, incidence of hyperglycemia, incidence of severe hyperglycemia, and daily insulin dose were all lower than those before the intervention [ SD of blood glucose (mmol/L): 1.83±1.11 vs. 2.10±1.13, MG (mmol/L): 8.87±2.03 vs. 9.75±1.37, median blood glucose (mmol/L): 9.12±1.67 vs. 10.17±0.48, MAGE (mmol/L): 0.66±0.31 vs. 0.78±0.32, LAGE (mmol/L): 4.95±3.64 vs. 5.58±3.10, CV of blood glucose: 16.00% (11.00%, 28.50%) vs. 18.00% (12.50%, 27.50%), hyperglycemia incidence: 47.31% vs. 74.66%, severe hyperglycemia incidence: 6.08% vs. 6.71%, daily insulin dose (U): 5.25 (0.00, 32.59) vs. 20.76 (0.00, 66.88)], with a significant decrease in daily insulin dose after the intervention ( P < 0.05); TP, ALB, Hb, CRP and WBC showed no significant changes before and after the intervention with Glucerna EN preparation. The improvement time of diarrhea symptoms after intervention was (3.50±1.41) days, and the Hart diarrhea score on the seventh day after intervention (4.88±3.48 vs. 10.00±3.38) and the Bristol Stool classification score on the third and seventh days after intervention (5.87±0.35, 5.50±0.53 vs. 6.50±0.53) were significantly lower than before the intervention (all P < 0.05). Before the intervention with Glucerna EN preparation, the classification of incontinence dermatitis was mainly classified as Grade 2 severity (71.43%); after the intervention, it significantly improved by the seventh day, with Grade 1 being the main classification (57.14%). Conclusion:The high MUFA and low carbohydrate formula has a positive effect on blood glucose control and diarrhea treatment in critically ill neurological patients.

Purpose::Under-foot impact loadings can cause serious lower limb injuries in many activities, such as automobile collisions and underbody explosions to military vehicles. The present study aims to compare the biomechanical responses of the mainstream vehicle occupant dummies with the human body lower limb model and analyze their robustness and applicability for assessing lower limb injury risk in underfoot impact loading environments.Methods::The Hybrid III model, the test device for human occupant restraint (THOR) model, and a hybrid human body model with the human active lower limb model were adopted for under-foot impact analysis regarding different impact velocities and initial lower limb postures.Results::The results show that the 2 dummy models have larger peak tibial axial force and higher sensitivity to the impact velocities and initial postures than the human lower limb model. In particular, the Hybrid III dummy model presented extremely larger peak tibial axial forces than the human lower limb model. In the case of minimal difference in tibial axial force, Hybrid III's tibial axial force (7.5 KN) is still 312.5% that of human active lower limb's (2.4 KN). Even with closer peak tibial axial force values, the biomechanical response curve shapes of the THOR model show significant differences from the human lower limb model.Conclusion::Based on the present results, the Hybrid III dummy cannot be used to evaluate the lower limb injury risk in under-foot loading environments. In contrast, potential improvement in ankle biofidelity and related soft tissues of the THOR dummy can be implemented in the future for better applicability.

Objective:To identify risk variables for prolonged postoperative length of stay (PPOLOS) in hip fracture patients by machine learning algorithms and construct Nomogram models.Methods:A retrospective case-control study was conducted to select 248 patients with hip fracture diagnosed and treated in Yingtan 184th Hospital from June 2019 to June 2023 by convenient sampling method. Two machine learning algorithms were used (least absolute shrinkage and selection operator, LASSO and support vector machine-Recursive Feature Elimination, SVM-RFE) to screen PPOLOS risk variables. Construct a Nomogram model to predict the risk of PPOLOS in patients with hip fracture based on intersection risk variables. The model was validated using internal data sets.Results:Among the 248 patients with hip fracture, there were 79 males and 169 females, aged (64.49 ± 8.02). The mean postoperative length of hospital stay of 248 patients was (7.98 ± 5.68) d, and the median was 7 d. LASSO algorithm identifies 7 risk variables, the SVM-RFE algorithm identified 8 risk variables. Intersectional risk variables were age, body mass index (BMI), Charlson comorbidity index (CCI), type of surgery, and central granulocytocyte ratio (NLR). Multivariate Logistic regression analysis(intersection risk variables) showed that age [ OR=1.649(1.235-2.202)], BMI [1.603(1.204-2.134)], CCI [ OR=1.670(1.236-2.258)], type of surgery [ OR=1.620(1.209-2.170), 1.699(1.243-2.321)], and NLR [ OR=3.258(2.299-4.617)] were independently associated with the risk of PPOLOS (all P<0.05). The results showed that the conformity index of the Nomogram model was 0.865 (95% CI=0.768-0.945). The area under the curve was 0.852 (95% CI=0.748-0.962). When the risk threshold was >0.08, it could provide significant clinical net benefit. The clinical impact curve showed effective identification of PPOLOS patients in high-risk groups. Conclusions:This Nomogram model can guide medical staff to make clinical diagnosis and treatment decisions as soon as possible to avoid risks, allocate medical resources rationally, and improve nursing quality.