BackgroundAggressive behavior in schizophrenic patients could result in legal disputes and public safety concerns. In patients with illness episodes of different numbers， there may exist differences in the association between levels of novel inflammatory indicators and aggressivity. ObjectiveTo investigate the differences in the correlation between levels of novel inflammatory indicators and aggressivity in patients with first-episode and recurrent schizophrenia， in order to search for inflammatory biomarkers to assess aggression level in schizophrenic patients. MethodsA total of 168 schizophrenic patients were selected as subjects， who were hospitalized for acute disease onset in Chaohu Hospital of Anhui Medical University from October 2022 to April 2024 as well as met the diagnostic criteria of Diagnostic and Statistical Manual of Mental Disorders， fifth edition （DSM-5）. Patients were divided into first-episode group （n=58） and recurrent group （n=110）. Meanwhile， 110 healthy controls from community who matched in age and gender with the patient group were recruited. All patients were evaluated with Modified Overt Aggression Scale （MOAS） and Positive and Negative Syndrome Scale （PANSS）. All subjects went through examination of the levels of novel inflammatory indicators， including neutrophil/lymphocyte ratio （NLR）， monocyte/lymphocyte ratio （MLR）， platelet/lymphocyte ratio （PLR）， neutrophil/high-density lipoprotein ratio （NHR）， monocyte/high-density lipoprotein ratio （MHR） and platelet/high-density lipoprotein ratio （PHR）. Spearman correlation analysis was adopted to investigate the correlation between levels of novel inflammatory indicators and the total score of MOAS in patients with first-episode and recurrent schizophrenia. ResultsThe levels of NLR， MLR， PLR， NHR， MHR and PHR in first-episode group were higher than those in control group （adjusted P<0.01）. The levels of NLR， MLR， NHR， MHR and PHR in recurrent group were higher than those in control group （adjusted P<0.01）. No significant difference was observed in the comparison in the levels of six novel inflammatory indicators between first-episode group and recurrent group （adjusted P>0.05）. Spearman correlation analysis showed， the MOAS total score of recurrent group was positively correlated with the levels of NLR， MLR and PLR （r=0.234， 0.192， 0.243， P<0.05）. There was no statistical significance in the correlation between MOAS total score and levels of six novel inflammatory indicators in first-episode group （P>0.05）. ConclusionAmong patients with first-episode and recurrent schizophrenia， the correlation between levels of novel inflammatory indicators and aggressivity could differ. NLR， MLR and PLR might be the biomarkers for assessing aggression level in recurrent schizophrenic patients. ［Funded by Anhui Provincial Natural Science Foundation （number， 2108085MH275）］

ObjectiveTo investigate the effect of 1，25（OH）₂D₃ on the level of peroxisome proliferator-activated receptor-γ （PPAR-γ） in the liver， the phenotype of hepatic macrophages， and liver inflammation in a rat model of nonalcoholic steatohepatitis （NASH）， as well as the mechanism of 1，25（OH）₂D₃ improving liver inflammation. MethodsAfter 1 week of adaptive feeding， 24 specific pathogen-free Wistar rats were randomly divided into normal group ［choline-supplemented L-amino acid-defined （CSAA） diet］， normal+1，25（OH）₂D₃ group ［CSAA diet+1，25（OH）₂D₃］， model group ［choline-deficient L-amino acid-defined diet （CDAA） diet］， and model+1，25（OH）₂D₃ group ［CDAA diet+1，25（OH）₂D₃］， with 6 rats in each group. The dose of 1，25（OH）₂D₃ was 5 μg/kg for intraperitoneal injection twice a week for 12 weeks. The serum levels of aspartate aminotransferase （AST） and alanine aminotransferase （ALT） were measured， liver histopathology was observed， and SAF score was assessed. M1 hepatic macrophages and M2 hepatic macrophages were measured to analyze in the change in the phenotype of hepatic macrophages， and ELISA was used to measure the levels of tumor necrosis factor-α （TNF-α）， interleukin-1β （IL-1β）， interleukin-4 （IL-4）， and interleukin-10 （IL-10） in liver tissue， and qPCR was used to measure the mRNA level of PPAR-γ. The two-factor analysis of variance was use for comparison between groups， and the least significant difference t-test was used for further comparison； the Pearson method was used for correlation analysis. ResultsCompared with the normal group， the model rats with CDAA diet-induced NASH had significant increases in the serum levels of AST and ALT （P=0.019 and P<0.001）， the SAF score of liver histopathology （P<0.001）， the level of M1 hepatic macrophages （P<0.001）， and the ratio of M1 and M2 hepatic macrophages （P<0.001）， as well as a significant increase in the level of TNF-α （P<0.001） and a significant reduction in the level of IL-4 in liver tissue （P=0.025）. The 1，25（OH）₂D₃ group had significant reductions in the serum levels of ALT （P<0.001）， the SAF score of liver histopathology （P<0.001）， the level of M1 hepatic macrophages （P<0.001）， and the ratio of M1 and M2 hepatic macrophages （P=0.001）， the level of IL-1β （P<0.001） and a significant increase in the level of M2 hepatic macrophages （P=0.017）， the level of IL-10 （P=0.039）， the level of IL-4 （P<0.001）， the level of PPAR-γ （P=0.016）. There were significant interactions between CDAA diet-induced NASH model and 1，25（OH）₂D₃ in serum the levels of AST and ALT （P=0.007 and P=0.008）， the SAF scores of liver histopathology （P<0.001）， the level of M1 hepatic macrophages （P<0.001）， the level of M2 hepatic macrophages （P=0.008）， the ratio of M1 and M2 of hepatic macrophages （P=0.005）， the level of TNF-α （P<0.001）， the level of IL-10 （P=0.038）， the level of IL-4 （P<0.001） and the level of PPAR-γ （P=0.009）. The correlation analysis showed that PPAR-γ was negatively correlated with the ratio of M1 and M2 hepatic macrophages （r=-0.415， P=0.044） and was positively correlated with M2 hepatic macrophages （r=0.435， P=0.033）， IL-10 （r=0.433， P=0.035）， and IL-4 （r=0.532， P=0.007）. ConclusionThis study shows that 1，25（OH）₂D₃ improves liver inflammation in NASH by activating PPAR-γ to regulate the phenotypic transformation of hepatic macrophages.

Background: and Purpose This study aimed to investigate the association between residual inflammatory risk (RIR) and vulnerable plaques using high-resolution magnetic resonance imaging (HRMRI) in symptomatic intracranial atherosclerotic stenosis (ICAS). Methods: This retrospective study included 70%–99% symptomatic ICAS patients hospitalized from January 2016 to December 2022. Patients were classified into four groups based on high-sensitivity C-reactive protein (hs-CRP) and low-density lipoprotein cholesterol (LDL-C): residual cholesterol inflammatory risk (RCIR, hs-CRP ≥3 mg/L and LDL-C ≥2.6 mmol/L), RIR (hs-CRP ≥3 mg/L and LDL-C <2.6 mmol/L), residual cholesterol risk (RCR, hs-CRP <3 mg/L and LDL-C ≥2.6 mmol/L), and no residual risk (NRR, hs-CRP <3 mg/L and LDL-C <2.6 mmol/L). Vulnerable plaque features on HRMRI included positive remodeling, diffuse distribution, intraplaque hemorrhage, and strong enhancement. Results: Among 336 included patients, 21, 60, 58, and 197 were assigned to the RCIR, RIR, RCR, and NRR groups, respectively. Patients with RCIR (adjusted odds ratio [aOR], 3.606; 95% confidence interval [CI], 1.346–9.662; P=0.011) and RIR (aOR, 3.361; 95% CI, 1.774–6.368, P<0.001) had higher risks of strong enhancement than those with NRR. Additionally, patients with RCIR (aOR, 2.965; 95% CI, 1.060–8.297; P=0.038) were more likely to have intraplaque hemorrhage compared with those with NRR. In the sensitivity analysis, RCR (aOR, 2.595; 95% CI, 1.201–5.608; P=0.015) exhibited an additional correlation with an increased risk of intraplaque hemorrhage. Conclusion In patients with symptomatic ICAS, RIR is associated with a higher risk of intraplaque hemorrhage and strong enhancement, indicating an increased vulnerability to atherosclerotic plaques.

ObjectiveTo evaluate the clinical efficacy and safety of Qidan Tangshen Granules （芪丹糖肾颗粒， QTG） in the treatment of early diabetic kidney disease （DKD） with qi deficiency， blood stasis， and kidney deficiency syndrome， and to explore its mechanism. MethodsA double-blind， double-simulated method was used to enroll 200 patients with early DKD and qi deficiency， blood stasis， and kidney deficiency syndrome. Patients were randomly assigned in a 1∶1 ratio to the treatment group （100 cases） and the control group （100 cases）. The treatment group received QTG plus a valsartan capsule simulant， while the control group received valsartan capsules plus a QTG simulant， both for 12 weeks. The primary outcome was the urinary albumin-to-creatinine ratio （UACR）. Secondary outcomes included estimated glomerular filtration rate （eGFR）， fasting blood glucose （FBG）， 2-hour postprandial blood glucose （PBG）， glycated hemoglobin （HbA1c）， and traditional Chinese medicine （TCM） syndrome scores （including individual symptom scores for fatigue， dull complexion， soreness and weakness of the waist and knees， headache and chest pain， irritability， spontaneous sweating， thirst and polydipsia， polyphagia， polyuria， numbness of the limbs， and the total TCM syndrome score）. Oxidative stress markers including serum 8-hydroxy-2'-deoxyguanosine （8-OHDG）， 3-nitrotyrosine （3-NT）， and superoxide dismutase （SOD） were also assessed. Clinical efficacy and TCM syndrome efficacy were evaluated after treatment， and routine blood tests， urinalysis， and liver function tests were conducted and adverse reaction during the tria was recorded to assess safety. ResultsA total of 191 patients completed the study （95 in the treatment group and 96 in the control group）. The treatment group showed significant reductions in UACR， FBG， PBG， and HbA1c levels after treatment （P＜0.05 or P＜0.01）. The single TCM symptom scores except for polyphagia and total TCM syndrome scores significantly decreased （P＜0.05 or P＜0.01）. Compared to the control group， the treatment group had signi-ficantly lower UACR， FBG， PBG levels， and total TCM syndrome scores， sinlge symptoms scores except for polyphagia and limb numbness （P＜0.05 or P＜0.01）. Among 40 randomly selected patients （21 cases in the treatment group and 19 cases in the control group） for oxidative stress analysis， there were no significant differences in SOD， 3-NT， and 8-OHDG levels before and after treatment within or between groups （P＞0.05）. The overall effective rate in the treatment group was 64.2% （61/95） and 39.6% （38/96） in the control group， while the TCM syndrome efficacy rates were 80.0% （76/95） and 24.0% （23/96）， respectively， with the treatment group showing superior efficacy （P＜0.01）. No significant differences were observed in routine blood tests， urinalysis， or liver function indices before and after treatment in either group （P＞0.05）. The incidence of adverse reactions was 8.4% （8/95） in the treatment group and 9.4% （9/96） in the control group， with no statistically significant difference （P＞0.05）. ConclusionQTG can effectively reduce UACR and blood glucose levels， alleviate clinical symptoms， and improve clinical efficacy in patients with early DKD with qi deficiency， blood stasis， and kidney deficiency syndrome. The treatment is well-tolerated and safe， with no significant impact on oxidative stress markers.

BACKGROUND:Crosslinked sodium hyaluronate gel has good mechanical property,biocompatibility,and biodegradability,and can be used as an isolated protective material in tumor radiation therapy to protect endangered organs from damage caused by excess radiation dose. OBJECTIVE:To investigate the safety and efficacy of crosslinked sodium hyaluronate gel in reducing the dose of radiation to dangerous organs during brachytherapy. METHODS:A total of 16 specific pathogen-free Kunming mice of the same age and similar body weight were selected as experimental subjects and divided into experimental group and control group by the random number table method,with 8 mice in each group.125I seeds were implanted subcutaneously in the back of mice in the experimental group,and then crosslinked sodium hyaluronate gel was injected around the radioactive particles.Only 125I seeds were implanted subcutaneously in the back of mice in the control group.After injection,the distance between the radioactive particles and the epidermis was measured by spiral CT scan,and the surface radiation dose was measured by radiation dosimeter.Within 10 weeks after injection,the growth state,survival rate,skin radiation damage,and gel retention of mice were observed. RESULTS AND CONCLUSION:(1)Spiral CT scan showed that the implanted gel was relatively concentrated and created an effective distance between the radioactive seeds and the epidermis.The body surface radiation dose of the experimental group was significantly lower than that of the control group(P<0.01).(2)During the experimental observation period,mice in both groups survived;mice in the control group showed obvious irritability and other unstable behavior in the late experimental period,and some mice in the experimental group showed similar behavior.The daily food intake of mice in the two groups had no significant change,and the body mass showed the same increasing trend.After implantation of radioactive seeds,the two groups of mice showed different degrees of radioactive skin injury.From day 23 after injection to the end of the experiment,the skin radiation injury score of the experimental group was lower than that of the control group(P<0.01).At week 10 after implantation,6 mice in the experimental group had no obvious gel residue under their skin,and 2 mice had a very small amount of scattered gel-like samples under their skin.(3)Therefore,the crosslinked sodium hyaluronate injection technique can increase the space between the radioactive target area of 125I seeds and the organ at risk outside the target through physical space occupying,which can effectively reduce the dose of the organ at risk,and play a role in the isolation and protection of the organ at risk.

BACKGROUND:Studies have shown that ischemia-induced cellular autophagy dysfunction is a key factor in brain injury.Autophagy related genes 6(ATG6),microtubule-associated protein 1 light chain(LC3),p62,and other autophagy key proteins are involved in the processes such as neuronal axonal degeneration,death,and intracellular homeostasis maintenance,playing an important role in the recovery of neural function. OBJECTIVE:To review the research progress in the role of cellular autophagy in cerebral ischemic injury and the regulatory mechanism of traditional Chinese medicine. METHODS:The first author used"ischemic stroke,brain tissue injury,cellular autophagy,signaling pathways,traditional Chinese medicine compounds,terpenoids,alkaloids,flavonoids,saponins,lignans,phthalates"as Chinese and English keywords respectively to search for literature on autophagy,cerebral ischemic injury,and the regulatory mechanisms of traditional Chinese medicine from China National Knowledge Infrastructure(CNKI)and PubMed databases from January 2016 to February 2024.Literature that is not highly relevant,repetitive,or outdated was excluded.A total of 1 746 relevant literature were retrieved,and 92 articles were ultimately included. RESULTS AND CONCLUSION:Numerous studies have confirmed that autophagy plays an important role in cerebral ischemic injury.Moderate autophagy can promote cell survival,while excessive autophagy exacerbates brain injury.Traditional Chinese medicine can regulate the expression of autophagy related proteins,inhibit neuronal necrosis and apoptosis,and exert neuroprotective effects at different stages of cerebral ischemia by regulating signaling pathways such as PI3K/Akt/mTOR,AMPK-mTOR,and mitogen activated protein kinase.

ObjectiveTo explore the process and guidelines for ethical review in decentralized drug clinical trials， promote clinical trial progress， and ensure drug development progress. MethodsThe key points of the ethical review were summarized by studying the relevant laws and regulations on decentralized drug clinical trials， analyzing the advantages and challenges of decentralized drug clinical trials， and combining the experience of the ethics committee of the institution in reviewing decentralized drug clinical trials. ResultsRelevant laws and regulations were the basis for the ethical review， and the ethics committee should adopt appropriate review methods based on regulations and hospital ethical standard operating procedures. The ethics committee should focus on the feasibility， applicability， and rationality， the adequacy of informed consent， the protection of rights and interests and privacy of subjects， as well as the qualification and standard operating procedures of electronic platforms for conducting decentralized drug clinical trials. ConclusionDecentralized drug clinical trials are in their early stages and urgently require guidance from relevant laws and regulations. Ethical review is also constantly being refined through exploration. It is necessary to supervise the implementation of responsibilities by all parties， pay attention to the rights and interests of subjects， and gradually promote the implementation of decentralized drug clinical trials.

The Expert Consensus on Clinical Application of Qinbaohong Zhike Oral Liquid in Treatment of Acute Bronchitis and Acute Attack of Chronic Bronchitis （GS/CACM 337-2023） was released by the China Association of Chinese Medicine on December 13^th， 2023. This expert consensus was developed by experts in methodology， pharmacy， and Chinese medicine in strict accordance with the development requirements of the China Association of Chinese Medicine （CACM） and based on the latest medical evidence and the clinical medication experience of well-known experts in the fields of respiratory medicine （pulmonary diseases） and pediatrics. This expert consensus defines the application of Qinbaohong Zhike oral liquid in the treatment of cough and excessive sputum caused by phlegm-heat obstructing lung， acute bronchitis， and acute attack of chronic bronchitis from the aspects of applicable populations， efficacy evaluation， usage， dosage， drug combination， and safety. It is expected to guide the rational drug use in medical and health institutions， give full play to the unique value of Qinbaohong Zhike oral liquid， and vigorously promote the inheritance and innovation of Chinese patent medicines.

Objective To determine the prognostic biomarkers and new therapeutic targets of the lung adenocarcinoma (LUAD), based on which to establish a prediction model for the survival of LUAD patients. Methods An integrative analysis was conducted on gene expression and clinicopathologic data of LUAD, which were obtained from the UCSC database. Subsequently, various methods, including screening of differentially expressed genes (DEGs), Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis and Gene Set Enrichment Analysis (GSEA), were employed to analyze the data. Cox regression and least absolute shrinkage and selection operator (LASSO) regression were used to establish an assessment model. Based on this model, we constructed a nomogram to predict the probable survival of LUAD patients at different time points (1-year, 2-year, 3-year, 5-year, and 10-year). Finally, we evaluated the predictive ability of our model using Kaplan-Meier survival curves, receiver operating characteristic (ROC) curves, and time-dependent ROC curves. The validation group further verified the prognostic value of the model. Results The different-grade pathological subtypes' DEGs were mainly enriched in biological processes such as metabolism of xenobiotics by cytochrome P450, natural killer cell-mediated cytotoxicity, antigen processing and presentation, and regulation of enzyme activity, which were closely related to tumor development. Through Cox regression and LASSO regression, we constructed a reliable prediction model consisting of a five-gene panel (MELTF, MAGEA1, FGF19, DKK4, C14ORF105). The model demonstrated excellent specificity and sensitivity in ROC curves, with an area under the curve (AUC) of 0.675. The time-dependent ROC analysis revealed AUC values of 0.893, 0.713, and 0.632 for 1-year, 3-year, and 5-year survival, respectively. The advantage of the model was also verified in the validation group. Additionally, we developed a nomogram that accurately predicted survival, as demonstrated by calibration curves and C-index. Conclusion We have developed a prognostic prediction model for LUAD consisting of five genes. This novel approach offers clinical practitioners a personalized tool for making informed decisions regarding the prognosis of their patients.

It is believed that Shengyang Yiwei Decoction （升阳益胃汤， SYD） is effective in regulating the flow of Qi （气）， and can treat various diseases caused by the disorder of the spleen and stomach Qi. In clinical practice， based on the pathological characteristics of children often having insufficient spleen， and adhering to the principle of treating different diseases with the same method， the focus is placed on the core pathogenesis of spleen and stomach Qi disharmony. We use SYD in various pediatric conditions such as allergic rhinitis， post COVID-19 condition， urethral syndrome， and dysfunctional uterine bleeding in adolescence， and emphasize the treatment is flexibly tailored to the symptoms.