BACKGROUND:Agomelatine is a clinically proven treatment for neuropsychiatric symptoms,such as anxiety and depression.Furthermore,our previous study has demonstrated that agomelatine ameliorates cognitive behaviors,hippocampal synaptic plasticity,and brain pathology in a mouse model of Alzheimer's disease.However,it remains unclear whether agomelatine can improve anxiety and depression-like behaviors in Alzheimer's disease model mice. OBJECTIVE:To investigate the improving effects of agomelatine on anxiety-and depression-like behaviors in APP/PS1 transgenic mice and its underlying molecular mechanisms. METHODS:(1)Eighteen APP/PS1 transgenic mice were randomly divided into model control group(n=9)and model intervention group(n=9).Another wild-type mice were randomized into control group(n=9)and intervention group(n=9).Model intervention group and intervention group were intraperitoneally injected with 10 mg/kg agomelatine per day for 31 continuous days.Behavioral experiments,including the elevated cross maze and forced swimming tests,and mRNA sequencing of the hippocampus were then performed.(2)Mouse hippocampal neuronal cell lines(HT22)and brain microvascular endothelial cell lines(bEnd.3)were cultured and divided into four groups:blank group without any drug,drug group with 20 μmol/L agomelatine,model group with 10 μmol/L β-amyloid 1-42,and experimental group with 10 μmol/L β-amyloid 1-42+20 μmol/L agomelatine.After 24 hours of incubation,protein expression of S416p-tau and S9p-GSK3β in HT22 cells was detected by immunoblotting,and protein expression of low-density lipoprotein receptor-related protein 1 and glycosylation end-product receptor in bEnd.3 cells was detected by immunoblotting. RESULTS AND CONCLUSION:In the elevated plus maze test,the time spent in the open arms(P＜0.01)and the entries into open arms(P＜0.05)in the mice of model control group were evidently lower than those in the control group,whereas those were obviously increased in the model intervention group compared with the model control group(P＜0.05).Forced swimming test results showed that the immobile time exhibited a marked increase in the model control group compared with the control group(P＜0.05),but it was significantly decreased in the model intervention group compared with the model control group(P＜0.05).Hippocampal tissue mRNA sequencing showed that agomelatine enhanced the expression of low-density lipoprotein receptor-related protein 1 in the hippocampus of APP/PS1 mice.Western blot analysis revealed that the level of S416p-tau in HT22 cells was higher in the model group than the blank group(P＜0.05),while it was markedly decreased in the experimental group compared with the model group(P＜0.05);the level of S9p-GSK3β in HT22 cells was higher in the drug group than the blank group(P＜0.05)as well as higher in the experimental group than the model group(P＜0.05).Moreover,the expression of low-density lipoprotein receptor-related protein 1 in bEnd.3 cells was higher in the experimental group than the model group(P＜0.05).To conclude,agomelatine can alleviate anxiety-and depression-like behaviors in Alzheimer's disease mice by promoting the clearance of β-amyloid and phosphorylated tau.

Yuejuwan is a classic formula widely used by doctors to relieve liver and depression， with precise clinical efficacy in traditional Chinese medicine （TCM）. The authors used bibliometric methods to collect and collate 495 ancient data related to Yuejuwan， and 105 valid data were screened out， involving 68 ancient Chinese medical books. After systematic verification of the origin of the formula of Yuejuwan， the main treatment symptoms， the principle of the formula， the composition of the drug， the dosage， the preparation method， the decoction method， and other information， the results showed that Yuejuwan originated from the Danxi Xinfa （《丹溪心法》） of the Yuan Dynasty by ZHU Zhenheng， and it is composed of five medicines， namely Atractylodis Rhizoma， Cyperi Rhizom， Chuanxiong Rhizoma， Massa Medicata Fermentata， and Gardeniae Fructus. In terms of drug base， Atractylodis Rhizoma， Cyperi Rhizom， Chuanxiong Rhizoma， and Gardeniae Fructus are in line with the records in the 2020 edition of Chinese Pharmacopoeia， and Massa Medicata Fermentata is used. The preparation method is as follows： Massa Medicata Fermentata and Gardeniae Fructus are fried， and Cyperi Rhizoma is roasted in vinegar. Chuanxiong Rhizoma is used in the raw form， and Atractylodis Rhizoma is prepared with rice swill. The formula can regulate Qi and relieve depression and broaden the middle and remove fullness. It is clinically used for the treatment of six types of depression syndromes， chest and diaphragm plumpness， abdominal distension and leg acid， acid swallowing and vomiting， eating and drinking disharmony， toothache， mouth and tongue sores， and other diseases. The most used dosage of the formula in the ancient records through the ages is converted into the modern dosage， namely 3.05 g Atractylodis Rhizoma， 3.05 g Cyperi Rhizoma， 3.05 g Chuanxiong Rhizoma， 3.05 g Massa Medicata Fermentata， and 3.05 g Gardeniae Fructus， and the daily dosage is 15.25 g. The converted dosage is similar to that recorded in the 2020 edition of the Chinese Pharmacopoeia. The formula is in pill form， and medicine should be taken with lukewarm boiled water after the meal. Through the excavation of the ancient literature related to Yuejuwan， the key information of the formula is identified， with a view to providing a more accurate reference for the clinical application of Yuejuwan and subsequent in-depth investigation.

Yuejuwan is a classic formula widely used by doctors to relieve liver and depression， with precise clinical efficacy in traditional Chinese medicine （TCM）. The authors used bibliometric methods to collect and collate 495 ancient data related to Yuejuwan， and 105 valid data were screened out， involving 68 ancient Chinese medical books. After systematic verification of the origin of the formula of Yuejuwan， the main treatment symptoms， the principle of the formula， the composition of the drug， the dosage， the preparation method， the decoction method， and other information， the results showed that Yuejuwan originated from the Danxi Xinfa （《丹溪心法》） of the Yuan Dynasty by ZHU Zhenheng， and it is composed of five medicines， namely Atractylodis Rhizoma， Cyperi Rhizom， Chuanxiong Rhizoma， Massa Medicata Fermentata， and Gardeniae Fructus. In terms of drug base， Atractylodis Rhizoma， Cyperi Rhizom， Chuanxiong Rhizoma， and Gardeniae Fructus are in line with the records in the 2020 edition of Chinese Pharmacopoeia， and Massa Medicata Fermentata is used. The preparation method is as follows： Massa Medicata Fermentata and Gardeniae Fructus are fried， and Cyperi Rhizoma is roasted in vinegar. Chuanxiong Rhizoma is used in the raw form， and Atractylodis Rhizoma is prepared with rice swill. The formula can regulate Qi and relieve depression and broaden the middle and remove fullness. It is clinically used for the treatment of six types of depression syndromes， chest and diaphragm plumpness， abdominal distension and leg acid， acid swallowing and vomiting， eating and drinking disharmony， toothache， mouth and tongue sores， and other diseases. The most used dosage of the formula in the ancient records through the ages is converted into the modern dosage， namely 3.05 g Atractylodis Rhizoma， 3.05 g Cyperi Rhizoma， 3.05 g Chuanxiong Rhizoma， 3.05 g Massa Medicata Fermentata， and 3.05 g Gardeniae Fructus， and the daily dosage is 15.25 g. The converted dosage is similar to that recorded in the 2020 edition of the Chinese Pharmacopoeia. The formula is in pill form， and medicine should be taken with lukewarm boiled water after the meal. Through the excavation of the ancient literature related to Yuejuwan， the key information of the formula is identified， with a view to providing a more accurate reference for the clinical application of Yuejuwan and subsequent in-depth investigation.

OBJECTIVE To provide a reference for the selection of anti-infection schemes and pharmaceutical monitoring of pulmonary infection due to Alternaria alternata after renal transplantation. METHODS The clinical pharmacist was involved in the anti-infective treatment of a patient with pulmonary infection caused by A. alternata after renal transplantation. After considering the patient’s clinical symptoms， laboratory test results， and pertinent literature， clinical pharmacists determined that the patient may have developed pulmonary infection as a result of respiratory allergy due to A. alternata. The potential for infections from both Legionella and adenovirus remained a possibility. Oral administration of Voriconazole tablets was recommended for fungal therapy， while Moxifloxacin tablets were suggested for treating Legionella. Additionally， it was advised to lower the dosage of tacrolimus and stop using ganciclovir. The pharmacists meticulously tracked the patient’s voriconazole trough levels and any adverse effects that might arise during the therapy. RESULTS The physician endorsed the clinical pharmacist’s recommendations， and the patient’s status was steady， permitting discharge. CONCLUSIONS A. alternata is a potential pathogen for immunosuppressed patients， particularly when they also experience respiratory allergic reactions. Voriconazole can serve as the first-line treatment for anti-infection therapy. Clinical pharmacists ensure the patient medication safety by adjusting the dosage of voriconazole， extending the treatment course， monitoring liver and visual functions， and being vigilant about the interaction between voriconazole and immunosuppressants.

Objective:To investigate whether quercetin reduces neuroinflammation in epileptic rats by regulating high mobility group protein B1(HMGB1),receptor for advanced glycation end products(RAGE)and nuclear factor kappa-B(NF-κB),and to explore the possibility of HMGB1/RAGE/NF-κB pathway as a new target of quercetin.Methods:Twelve SD rats were randomly selected from 60 SD rats as healthy group,and the remaining rats were used to construct experimental models of epilepsy rats.Rats that were successfully modeled were divided into model group,high-dose quercetin group,low-dose quercetin group,quercetin+pathway activator group,with 12 rats in each group.Pathological changes of hippocampal tissue of rats were observed;neurobehavioral function of rats was evaluated;levels of tumor necrosis factor-α(TNF-α),IL-6 and IL-1β,and mRNA and protein expression levels of HMGB1,RAGE,NF-κB in hippocampal tissue of rats were detected.Results:Structure of hippocampus of rats in healthy group was complete;compared with healthy group,structure of hippocampal tissue of rats in model group was scattered,the number of surviving neurons was observably reduced,apoptotic index was observably increased,the Racine grade was observably increased,TNF-α,IL-1β,IL-6 contents and mRNA and protein expression levels of HMGB1,RAGE,NF-κB in hippocampal tissue were significantly increased;com-pared with model group,structure of hippocampal tissue of rats in low-and high-dose quercetin groups was relatively complete,the number of surviving neurons was observably increased,apoptotic index was observably decreased,the Racine grade was significantly decreased,TNF-α,IL-1β,IL-6 contents and mRNA and protein expression levels of HMGB1,RAGE,NF-κB were significantly re-duced,and the improvement effect of high-dose quercetin group was better;compared with high-dose quercetin group,the number of surviving neurons in quercetin+pathway activator group was significantly reduced,apoptotic index was significantly increased,the Ra-cine grade was significantly increased,TNF-α,IL-1β,IL-6 contents and mRNA and protein expression levels of HMGB1,RAGE,NF-κB in hippocampal tissue were significantly increased.Conclusion:Quercetin can effectively reduce neuroinflammation in epilep-tic rats by inhibiting the HMGB1/RAGE/NF-κB pathway and reducing the mRNA and protein expressions of related genes.

Objective:To explore the antipyretic effect and partial mechanism of the pushing Tianheshui manipulation on lipopolysaccharide(LPS)-induced fever in young New Zealand rabbits. Methods:Thirty 50-day-old New Zealand rabbits were randomly assigned to five groups,including a normal group,a model group,a Tuina(Chinese therapeutic massage)group,a Tuina control group,and a drug group,with 6 rabbits in each group.All groups except for the normal group received LPS injections through the marginal ear vein to induce fever.One hour post-modeling,the Tuina and Tuina control groups received pushing Tianheshui manipulation and pushing manipulation on the medial middle of the hind limbs,respectively,administered every hour for a total of 3 interventions.The drug group was given acetaminophen oral liquid via gavage.Anal temperature was recorded every 30 min for 4.0 h to monitor temperature changes among groups.At 4.0 h post-modeling,hypothalamus samples from each group were analyzed using Western blotting(WB)and real-time quantitative polymerase chain reaction(RT-qPCR)to measure the relative expression levels of α-melanocyte-stimulating hormone(α-MSH),melanocortin 4 receptor(MC4R),cyclic adenosine monophosphate(cAMP),protein kinase A(PKA),nuclear factor-κB p65(NF-κB p65),and interleukin(IL)-1β proteins and their mRNAs. Results:Compared to the model group,the Tuina group showed a significant reduction in the anal temperature from 3.5 h to 4.0 h post-modeling(P<0.05).The Tuina control group did not show a significant temperature reduction from 0.5 h to 4.0 h post-modeling(P>0.05).The drug group exhibited a significant temperature reduction from 1.5 h to 4.0 h post-modeling(P<0.05).At 4.0 h post-modeling,compared to the model group,the Tuina group showed significantly increased relative expression of α-MSH and MC4R proteins and mRNAs(P<0.05)and significantly decreased relative expression of cAMP,PKA,NF-κB p65,and IL-1β proteins and mRNAs in the hypothalamus tissue(P<0.05).No significant differences were observed in these parameters in the Tuina control group compared to the model group(P>0.05). Conclusion:Pushing Tianheshui manipulation demonstrated a significant antipyretic effect,potentially linked to point specificity.Its mechanism may involve the α-MSH-mediated cAMP/PKA/NF-κB pathway.

Objective:To analyze the clinical characteristics and prognosis of patients with myelodysplastic syndrome (MDS) with a bone marrow nucleated erythroid cell proportion of greater than or equal to 50% (MDS-E) .Methods:The clinical characteristics and prognostic factors of patients with MDS-E were retrospectively analyzed by collecting the case data of 1 436 newly treated patients with MDS diagnosed in the Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences from May 2014 to June 2023.Results:A total of 1 436 newly diagnosed patients with complete data were included in the study, of which 337 (23.5%) patients with MDS-E had a younger age of onset and lower neutrophil and platelet counts compared with those in patients with an erythroid cell proportion of less than 50% (MDS-NE) (all P<0.05). The proportion of MDS cases with ring sideroblasts (MDS-RS) was higher in the MDS-E group than in the MDS-NE group, and multi-hit TP53 mutations were more enriched in the MDS-E group than in the MDS-NE group (all P<0.05). Among patients with MDS-RS, the frequency of complex karyotypes and the TP53 mutation rate were significantly lower in the MDS-E group than in the MDS-NE group (0 vs 11.9%, P=0.048 and 2.4% vs 15.1%, P=0.053, respectively). Among patients with TP53 mutations, the frequencies of complex karyotypes and multi-hit TP53 mutations were significantly higher in the MDS-E group than in the MDS-NE group (87.5% vs 64.6%, P=0.003 and 84.0% vs 54.2%, P<0.001, respectively). Survival analysis of patients with MDS-RS found that the overall survival (OS) in the MDS-E group was better than that in the MDS-NE group [not reached vs 63 (95% CI 53.3-72.7) months, P=0.029]. Among patients with TP53 mutations and excess blasts, the OS in the MDS-E group was worse than that in the MDS-NE group [6 (95% CI 2.2-9.8) months vs 12 (95% CI 8.9-15.1) months, P=0.022]. Multivariate analysis showed that age of ≥65 years ( HR=2.47, 95% CI 1.43-4.26, P=0.001), mean corpuscular volume (MCV) of ≤100 fl ( HR=2.62, 95% CI 1.54-4.47, P<0.001), and TP53 mutation ( HR=2.31, 95% CI 1.29-4.12, P=0.005) were poor prognostic factors independent of the Revised International Prognostic Scoring System (IPSS-R) prognosis stratification in patients with MDS-E. Conclusion:Among patients with MDS-RS, MDS-E was strongly associated with a lower proportion of complex karyotypes and TP53 mutations, and the OS in the MDS-E group was longer than that in the MDS-NE group. Among patients with TP53 mutations, MDS-E was strongly associated with complex karyotypes and multi-hit TP53 mutations, and among TP53-mutated patients with excess blasts, the OS in the MDS-E group was shorter than that in the MDS-NE group. Age of ≥65 years, MCV of ≤100 fl, and TP53 mutation were independent adverse prognostic factors affecting OS in patients with MDS-E.

Objective To investigate the real-world factors influencing the clinical outcome of Febrile neu-tropenia(FN)in oncology patients.Methods We conducted a retrospective analysis of clinical data from 130 FN patients admitted to our hospital between January 2020 and December 2022.The patients were categorized into three groups based on their clinical efficacy:cured group,effective group,and ineffective group.A comparison was made among the three groups regarding general data and laboratory examination results.Univariate and ordered multicategorical logistic regression analyses were performed to identify factors affecting the clinical efficacy of FN.Results The overall effective rate of FN in our hospital was 86.15%.Univariate analysis revealed statistically significant differences among the three patient groups regarding the duration of granulomatous defects,Physical Status Score(PS Score),procalcitonin(PCT)levels,and timing of administration(P＜0.05).Ordinal multicat-egorical logistic regression analysis demonstrated that patients with PS scores＜2,granulomatous defects lasting less than 7 days,and PCT levels below 0.5 ng/mL exhibited better clinical treatment outcomes.Conclusion In the management of FN,it is crucial to prioritize patients with high PS scores and elevated PCT levels while optimizing drug utilization to enhance clinical efficacy.Timely intervention should be implemented to address granulopathy and improve overall clinical outcomes.

Objective:To describe and analyze suicide risk of patients with schizophrenia,major depressive disorder,and bipolar disorder.Methods:A total of 2 016 patients with schizophrenia,903 patients with major de-pressive disorder,and 381 patients with bipolar disorder from inpatients,clinics,or communities who met the diag-nostic criteria of the Diagnostic and Statistical Manual of Mental Disorders,Fifth Edition were recruited.All patients were interviewed by psychiatrists using the Mini International Neuropsychiatric Interview to diagnose mental disor-ders and assess suicide risk,as well as Clinical-Rated Dimensions of Psychosis Symptom Severity(CRDPSS)to as-sess symptoms.Differences and risk factors of suicide risk among three types of mental disorders were explored u-sing multivariate logistic regression analysis.Results:In the past one month,37 patients with schizophrenia(1.8％),516 patients with major depressive disorder(57.1％),and 102 patients with bipolar disorder(26.8％)had suicide risk.Compared with patients with schizophrenia,suicide risk in patients with major depressive disorder(OR=36.50)and bipolar disorder(OR=20.10)increased.Female(OR=1.87),smoking(OR=1.76),family history of suicide(OR=5.09),higher score of CRDPSS hallucination(OR=1.80),and higher score of CRDPSS depression(OR=1.54)were risk factors of suicide risk of patients.Conclusions:Suicide risk of patients with ma-jor depressive disorder and bipolar disorder is higher than that of patients with schizophrenia.In clinical practice,it is important to regularly assess suicide risk of patients.Patients who experience symptoms of hallucination and de-pression should be paid more attention to.

Objective: To examine the association of hypertension onset age with diabetes, so as to provide insights into reducing the the risk of cardiovascular events. Methods: Permanent residents aged 35 to 75 years were selected through the program of early screening and comprehensive intervention for the high-risk cardiovascular disease population in Changning District and Baoshan District, Shanghai Municipality from 2016 to 2020. Demographic information, disease history, hypertension onset age, blood pressure and fasting blood glucose were collected through questionnaire surveys, physical examination and laboratory tests. The residents were divided into four groups based on the onset age of hypertension: <45, 45-<55, 55-<65 and ≥65 years old, and the residents with normal blood pressure were selected as control. The association of hypertension onset age with prediabetes and diabetes were identified using a multivariable logistic regression model. Results: A total of 25 228 residents were recruited, including 8 753 males (34.70%) and 16 475 females (65.30%). The prevalence of hypertension was 43.80%. There were 1 779, 3 274, 3 781 and 2 217 cases with hypertension onset age of <45, 45-<55, 55-<65 and ≥65 years old, respectively, and 14 177 residents with normal blood pressure. The prevalence of prediabetes and diabetes were 24.01% and 11.29%, respectively. Multivariable logistic regression analysis showed that after adjusting for confounding factors such as gender, marital status and educational level, compared with the normal blood pressure group, the risk of prediabetes was higher in the hypertension onset age groups of <45 (OR=1.345, 95%CI: 1.164-1.553), 45-<55 (OR=1.365, 95%CI: 1.212-1.536) and 55-<65 years old (OR=1.376, 95%CI: 1.239-1.527), and the risk of diabetes was higher in the hypertension onset age groups of <45 (OR=2.302, 95%CI: 1.906-2.775), 45-<55 (OR=2.349, 95%CI: 2.016-2.734), 55-<65 (OR=1.909, 95%CI: 1.667-2.184) and ≥65 years old (OR=1.315, 95%CI: 1.131-1.526). Conclusion There are statistically significant associations between hypertension onset age with prediabetes and diabetes.