Objective The aim of this randomized,double-blind,placebo-controlled trial was to evaluate the efficacy of the Saccharomyces boulardii (S.boulardii) power in preventing antibiotic-associated diarrhea (AAD) in hospitalized children with pneumonia.Methods Two hundred and forty-five hospitalized children with pneumonia were randomly divided into two groups,group 1 treated with antibiotics and S.boulardii power (n =104),and group 2 with antibiotics and placebo,along with S.boulardii power and zinc when suffered from diarrhea (n =141).All children received montmorillonite powder and fluid replacement therapy for diarrhea.The stool frequency and consistency were observed.Diarrhea incidence,diarrhea and pneumonia duration of treatment,and therapeutic effect were recorded.Results AAD is more prevalent in group 2 than in group 1 (P ＜0.05).A 55.7％ relative risk reduction in AAD was seen in group 1 compared with group 2 (RR =0.443,95％CI 0.233 ～ 0.845,P =0.012).Patients with preventive treatment of S.boulardii power in broup 1 had lower AAD incidence compared with those in group 2 (P ＜ 0.05).Both the diarrhea and pneumonia duration of treatment in group 1 were shorter than that in group 2(P =0.001 for diarrhea duration,P =0.030 for pneumonia duration,respectively).No drug related adverse reactions were found during the observation period.Conclusion Preventive use of S.boulardii power may effectively reduce the risk of AAD,improve therapeutic effect,and shorten hospital stays for hospitalized children with pneumonia.

Objective:To investigate the reference value of ultrasonography (US) image features, elastography and serum thyroid stimulating hormone (TSH) levels in preoperative diagnosis of differentiated thyroid carcinoma (DTC).Methods:Retrospective analysis was conducted to collect clinical data of patients undergoing thyroid surgery in the Fourth Affiliated Hospital of Harbin Medical University from September 2018 to January 2020. All patients underwent conventional ultrasound, elastography examination and serum TSH level measurement before surgery; patients were divided into benign group and DTC group according to the results of pathological results of the operation, and the US image features and elasticity score were analyzed by chi-square test and multivariate logistic regression to evaluate the causes of DTC; a multivariate logistic regression model was established and the receiver operating characteristic curve (ROC) was drawn with the regression model, by analyzing the area under the ROC curve (AUC), sensitivity, specificity and accuracy, the reference value of US image features, elastography and serum TSH levels in the preoperative diagnosis of DTC were judged.Results:Clinical data of 81 patients were collected, including 17 men and 64 women, aged (48.72 ± 10.58) years. In benign group, there were 37 cases, including 10 men and 27 women, with age of (53.24 ± 9.59) years; there were 44 patients in DTC group, including 7 men and 37 women, with age of (44.91 ± 9.95) years old, the age difference between benign group and DTC group was significant ( t = 3.822, P < 0.05), while the gender difference was not statistically significant (χ 2 = 1.498, P > 0.05). There were significant differences in the number, size, echo level, microcalcification, aspect ratio and elasticity score between benign group and DTC group (χ 2 = 49.000, 4.457, 32.111, 5.444, 4.457, 49.926, P < 0.05); multivariate logistic analysis showed that hypoecho, microcalcification, aspect ratio > 1 and elasticity score were risk factors for DTC ( OR = 8.042, 4.787, 4.160, 2.380, P < 0.05), the ROC curve of the multivariate logistic regression model showed that the AUC was 0.841 (95% CI = 0.743 - 0.939), sensitivity was 90.91%, specificity was 72.97%, and accuracy was 82.72%; the AUC of serum TSH level prediction of DTC showed that the AUC was 0.721 ( P < 0.05), sensitivity was 72.70%, specificity was 64.90%, accuracy was 54.30%, and TSH best cut-off value was 2.215 μU/ml. Conclusion:In the preoperative diagnosis of DTC, US image features, elastography and serum TSH levels are of important clinical reference value for diagnosis of DTC, and the establishment of multivariate logistic regression model is conducive in improving the clinicians prediction of the occurrence of DTC.

Objective Observe the effect of Liuwei Anshen Capsule on sleep improvement of aged sleep deprivation zebrafish model.Methods Sixty 18-month-old female zebrafish were randomly divided into blank group,model group,Liuwei Anshen group,and melatonin group.The zebrafish in the blank group were raised under normal lighting conditions,and the other three groups were constructed with continuous lighting for 3 days.Zebrafish in Liuwei Anshen group were treated with Liuwei Anshen capsule water solution 0.000 50 mg·mL-1 for 3 days on the basis of model group,and zebrafish in melatonin group were treated with melatonin aqueous solution 0.2 mg·mL-1 on the basis of model group for 3 days.After 3 days,the zebrafish behavior system was used to detect the resting time of zebrafish in each group.qRT-PCR method was used to detect cyclin 1a(per1a),cyclin2(per2),circadian motor output cycle 1a(clock1a),cryptochrome 1b(cry1b),and 5-hydroxyindoleacetic acid(5-htiaa)in each group of zebrafish and follicle-stimulating hormone beta(fshβ)gene expression levels.Western blot was used to detect the expression levels of estrogen receptorα(Esrα),Fshβand luteinizing hormone(Lh)in zebrafish in each group.HE staining was used to observe the ovary of zebrafish in each group.Results Compared with the zebrafish in the blank group,the resting time of the zebrafish in the model group decreased significantly(P<0.01)during the 24 hours of observation.After the intervention of Liuwei Anshen Capsule and melatonin,the resting time of the zebrafish was significantly increased.(P<0.01).Compared with the zebrafish in the blank group,the mRNA expressions of zebrafish circadian clock genes per1a,per2,clock1a,cry1b,5-htiaa,and fshβ all showed a downward trend after sleep deprivation(P<0.05,P<0.01).After the intervention of Liuwei Anshen Capsules,the mRNA expressions of per1,clock1a,cry1b,5-htiaa and fshβ were all up-regulated(P<0.05,P<0.01).Compared with the zebrafish in the blank group,the protein expressions of Esrα and Lh in the zebrafish of the model group were up-regulated(P<0.05),the expression of Fshβ protein was down-regulated(P<0.05),after the intervention of Liuwei Anshen Capsules,the above proteins did not change significantly.The ovarian tissue cells of the zebrafish in the blank group had normal morphology and a large number of primary oocytes,while the ovarian tissue cells of the zebrafish in the model group were damaged in morphology and the number of primary oocytes decreased,after the intervention of Liuwei Anshen Capsule and melatonin,the cell morphology of zebrafish ovarian tissue was still damaged to varying degrees,but the whole was relatively intact,and the number of primary oocytes increased.Conclusion The insomnia of aged zebrafish may be caused by multiple factors.Liuwei Anshen capsule has significant effects on estrogen level of rhythm gene and ovarian function of sleep-deprived aged zebrafish.

Objective:To explore the application of anterior esophageal wall full layer fixation and gastric tube guidance in total laparoscopic overlap method for intracorporeal esophagojejunostomy.Methods:Overlap esophagojejunostomy with anterior esophageal wall full layer fixation and gastric tube guidance is suitable for patients with advanced gastric cancer (clinical stage: cT1b~4aN0~3M0) and esophageal invasion <3 cm, who underwent radical total gastrectomy+ overlap esophagojejunostomy. The main operation procedure was performed as follows: A titanium clip was used for fixation of the full anterior wall of esophagus before overlap esophagojejunostomy, and the side‐to‐side esophagojejunostomy was performed with the linear stapler under the guidance of gastric tube. Then the titanium clip was removed after confirming that the correct cavity was entered. Finally, the common outlet was closed by two barbed sutures. A descriptive case series study was conducted. The clinical data of patients who underwent laparoscopic radical gastrectomy and overlap esophagojejunostomy with anterior esophageal wall full layer fixation and gastric tube guidance in Guangdong Provincial Hospital of Chinese medicine and the First Affiliated Hospital of Guangzhou University of Chinese medicine from May 2021 to June 2023 were retrospectively analyzed.Results:A total of 42 patients were collected, and all of them were successfully completed laparoscopic total radical gastrectomy without conversion to laparotomy or perioperative death. The esophagojejunostomy time, operative time, intraoperative blood loss was 17(5‐25) minutes, (258.8±38.0) minutes and 50(20‐200) ml, respectively. The incidence of esophageal false lumen was 0%, and there were no intraoperative complications. The time of gastric tube removal, initial fluid diet intake and the duration of postoperative hospital were 2(1‐5) , 4(1‐8) and 8(4‐21) days, respectively. There were no postoperative anastomotic hemorrhage, anastomotic stenosis and other related complications. One patient (2.38%) developed a Clavien‐Dindo IIIb complication, which was abdominal hemorrhage after operation. The second surgical exploration confirmed that the patient was bleeding due to gastroduodenal artery rupture. After intraoperative suture hemostasis, fluid expansion, blood transfusion and other treatments, the patient was discharged on the 15th day after the operation. Three patients (7.14%) developed Clavien‐Dindo grade II complications, including anastomotic leakage, chylous leakage and pulmonary infection, and were discharged after conservative treatment such as anti‐infection and prolonged retention of drainage tube.Conclusions:Laparoscopic overlap method for intracorporeal esophagojejunostomy with anterior esophageal wall fixation and gastric tube guidance can shorten the time of esophagojejunostomy and prevent the occurrence of false lumen, and do not increase anastomose‐related complications.

Objective To observe the effects of AnMeiDan(AMD),a representative formula of Peiyuan Guben Tranquilisation method,on the learning memory of zebrafish model of sleep deprivation(SD),and to explore the possible mechanism and the optimal apparent dose based on the Orexin signalling pathway.Methods 120 4-month-old wild-type AB line zebrafish were randomly divided into blank group,model group,AMD low-dose group(0.009 mg·mL-1·d-1),AMD medium-dose group(0.027 mg·mL-1·d-1),AMD high-dose group(0.081 mg·mL-1·d-1),and melatonin group(0.4 mg·mL-1·d-1).Zebrafish SD model was established by LED light induction method,24 h behavioural changes of zebrafish in each group were monitored by zebrafish behavioural tracking system,differences in learning and memory ability of zebrafish in each group were detected by T-maze,the state and number of neurons in the brain of zebrafish in each group were observed by Hematoxylin-Eosin(HE)staining method,the structural changes of neurons in the brain of zebrafish in each group were observed by transmission electron microscopy,and changes in neuron structure in the brain of zebrafish in each group were detected by ELISA method.The levels of Orexin A(OXA)and Orexin B(OXB)in zebrafish were detected by enzyme-linked immunosorbent assay(ELISA),and the protein and mRNA expression levels of OXA/p38 mitogen-activated protein kinase(P38 MAPK)/extracellular regulated protein kinase(ERK1/2)were detected by protein immunoblotting and real-time fluorescence quantitative assay(RT-PCR)in zebrafish.Results Compared with the blank group,the total number of rests,duration and distance were reduced in the model group(P<0.05),and the latency to enter the target region(OR)was prolonged(P<0.01);the number of neuronal cells was reduced,the nuclei were degenerated(P<0.01),cytoplasmic hyalinosis was increased(P<0.01),and light colouring was observed,the nuclei were collapsed,the nuclear membranes were ruptured and lysed,the chromatin was solidified,and the mitochondria were swollen and deformed with internal cavities,and lamellipod-like myelin-like structure was formed;the brain tissue OXA,OXA,and ERK1/2 expression levels of the mRNAs and the mRNAs of these signaling pathways were increased(P<0.01).brain tissue OXA and OXB proteins were significantly elevated,OXA mRNA and protein were significantly up-regulated,and P38 MAPK and ERK1/2 mRNA and protein were significantly down-regulated(P<0.01).Compared with the model group,the drug intervention could prolong the total resting exercise time of SD zebrafish(P<0.05);shorten the latency of zebrafish to reach OR(P<0.05);protect the structure and morphology of neuronal cells,and alleviate the damage of brain tissues;reduce the content of OXA and OXB in the brain tissues(P<0.01);and down-regulate the expression of OXA mRNA and protein(P<0.01),and up-regulate the P38 MAPK and ERK1/2 mRNA and protein expression of P38 MAPK and ERK1/2(P<0.01);and the quantity-effect relationship was obvious,and the effect of high dose of AMD was optimal.Conclusion AMD can improve the learning and memory ability in zebrafish SD model,and its mechanism may be related to the regulation of OXA/P38 MAPK/ERK1/2 signalling pathway and alleviation of neuronal damage in the brain,and the high dose group of AMD showed the best effect.

Objective:To explore the application of anterior esophageal wall full layer fixation and gastric tube guidance in total laparoscopic overlap method for intracorporeal esophagojejunostomy.Methods:Overlap esophagojejunostomy with anterior esophageal wall full layer fixation and gastric tube guidance is suitable for patients with advanced gastric cancer (clinical stage: cT1b~4aN0~3M0) and esophageal invasion <3 cm, who underwent radical total gastrectomy+ overlap esophagojejunostomy. The main operation procedure was performed as follows: A titanium clip was used for fixation of the full anterior wall of esophagus before overlap esophagojejunostomy, and the side‐to‐side esophagojejunostomy was performed with the linear stapler under the guidance of gastric tube. Then the titanium clip was removed after confirming that the correct cavity was entered. Finally, the common outlet was closed by two barbed sutures. A descriptive case series study was conducted. The clinical data of patients who underwent laparoscopic radical gastrectomy and overlap esophagojejunostomy with anterior esophageal wall full layer fixation and gastric tube guidance in Guangdong Provincial Hospital of Chinese medicine and the First Affiliated Hospital of Guangzhou University of Chinese medicine from May 2021 to June 2023 were retrospectively analyzed.Results:A total of 42 patients were collected, and all of them were successfully completed laparoscopic total radical gastrectomy without conversion to laparotomy or perioperative death. The esophagojejunostomy time, operative time, intraoperative blood loss was 17(5‐25) minutes, (258.8±38.0) minutes and 50(20‐200) ml, respectively. The incidence of esophageal false lumen was 0%, and there were no intraoperative complications. The time of gastric tube removal, initial fluid diet intake and the duration of postoperative hospital were 2(1‐5) , 4(1‐8) and 8(4‐21) days, respectively. There were no postoperative anastomotic hemorrhage, anastomotic stenosis and other related complications. One patient (2.38%) developed a Clavien‐Dindo IIIb complication, which was abdominal hemorrhage after operation. The second surgical exploration confirmed that the patient was bleeding due to gastroduodenal artery rupture. After intraoperative suture hemostasis, fluid expansion, blood transfusion and other treatments, the patient was discharged on the 15th day after the operation. Three patients (7.14%) developed Clavien‐Dindo grade II complications, including anastomotic leakage, chylous leakage and pulmonary infection, and were discharged after conservative treatment such as anti‐infection and prolonged retention of drainage tube.Conclusions:Laparoscopic overlap method for intracorporeal esophagojejunostomy with anterior esophageal wall fixation and gastric tube guidance can shorten the time of esophagojejunostomy and prevent the occurrence of false lumen, and do not increase anastomose‐related complications.

ObjectiveTo elucidate the potential mechanisms by which the classic prescription Anmeidan alleviates cognitive impairment in insomnia model rats through metabolic profiling. MethodsA total of 60 SD rats were randomly divided into six groups： blank group， model group， low-， medium-， and high-dose Anmeidan groups， and the Suvorexant group， with 10 rats in each group. Except for the blank group， the insomnia model was established in all other groups via intraperitoneal injection of para-chlorophenylalanine. The Suvorexant group was administered Suvorexant solution （30 mg·kg^-1·d^-1） by gavage， while the low-， medium-， and high-dose Anmeidan groups received Anmeidan decoction （4.55， 9.09， 18.18 g·kg^-1·d^-1） by gavage. The blank group received an equivalent volume of normal saline. The open field test was used to assess spatial exploration and anxiety/depressive-like behaviors in rats. Serum levels of epidermal growth factor （EGF）， brain-derived neurotrophic factor （BDNF）， and vasoactive intestinal peptide （VIP） were measured using enzyme-linked immunosorbent assay （ELISA）. Untargeted metabolomics was employed to identify differential metabolites in rat serum， and systematic biological methods were applied to analyze the potential targets and pathways of Anmeidan. ResultsCompared to the blank group， the model group exhibited significant reductions in total distance traveled， average speed， number of entries into the central area， time spent in the central area， and frequency of upright events （P<0.01）， along with significant decreases in VIP， EGF， and BDNF levels （P<0.05，P<0.01）. A total of 100 differential metabolites were identified between the model and blank groups. Compared to the model group， the low-， medium-， and high-dose Anmeidan groups showed significant increases in total distance traveled， average speed， number of entries into the central area， time spent in the central area， and frequency of upright events （P<0.05，P<0.01）， as well as a significant increase in VIP levels （P<0.05，P<0.01）. Anmeidan significantly reversed abnormal changes in 67 metabolites compared to the model group. A combined analysis identified 134 potential targets of Anmeidan， with network topology analysis suggesting that Caspase-3， B-cell lymphoma 2 （Bcl-2）， nuclear transcription factor-κB （NF-κB）， interleukin-1β （IL-1β）， interleukin-2 （IL-2）， matrix metalloproteinase-9 （MMP-9）， and Toll-like receptor 4 （TLR4）， among others， may serve as key targets of Anmeidan. Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway analysis revealed major enriched pathways， including the cyclic adenosine monophosphate （cAMP） signaling pathway， hypoxia inducible factor-1 （HIF-1） signaling pathway， and IL-17 signaling pathway. ConclusionThis study demonstrates that Anmeidan can recalibrate abnormal metabolic profiles in insomnia model rats to mitigate cognitive impairment， with its mechanisms of action potentially involving the regulation of immune-inflammatory responses， energy metabolism， and apoptosis-related pathways.

Objective To investigate the antibacterial effect and its preliminary mechanism of lavender essential oil on multi-drug resistant Acinetobacter baumannii.Methods Micro-dilution method was used to determine the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC)of lavender essential oil against multi-drug resistant Acinetobacter baumannii,and bactericidal kinetic study was employed to determine the onset and maintenance time of lavender essential oil.Meanwhile,the promoting and therapeutic effects of lavender essential oil on wound healing were observed in a mouse model of infection.Subsequently,crystal violet staining was used to determine the inhibition and clearance of multi-drug resistant Acinetobacter baumannii biofilm by lavender essential oil,and laser confocal microscopy was utilized to observe the survival of bacteria in biofilms.NanoDrop instrument was utilized to quantify the leakage of bacterial DNA nucleic acid and protein after intervention with 3 and 6 mg/mL lavender essential oil,and the leakage of bacterial potassium ion was measured by potassium ion test kit.Proteomics technology combined with bio-informatics were applied to explore the action mechanism of lavender essential oil against multi-drug resistant Acinetobacter baumannii.Results The MIC and MBC of lavender essential oil were both 6 mg/mL,which could kill almost all multi-drug resistant Acinetobacter baumannii at the time point of 120 min,and showed an obvious dose-and time-dependent manner.The overall animal model evaluation showed that both 3 and 6 mg/mL lavender essential oil could promote wound healing,and the curative effect was obvious.Further studies confirmed that 3 mg/mL lavender essential oil had a certain biofilm inhibitory effect on multi-drug resistant Acinetobacter baumannii,and 6 mg/mL also had a certain biofilm clearance effect under the same conditions.Meanwhile,when incubated at 37℃ for 1 h,the dose of 3 mg/mL could increase the leakage of DNA nucleic acid and protein,and significantly promote the efflux of potassium ions.Proteomic analysis suggested that the antibacterial effect of lavender essential oil may be related to affecting the oxidorereductase activity and cell metabolic process of multi-drug resistant Acinetobacter baumannii,and interfering with the biosynthesis of cell wall/membrane/envelope and other structures.Conclusion Lavender essential oil at 3 mg/mL can play an antibacterial effect against multi-drug resistant Acinetobacter baumannii,and its mechanism may be related to the destruction of bacterial biofilm and interference with bacterial metabolism.

ObjectiveTo investigate the mechanism by which Anmeidan improves learning and memory in insomnia rats by regulating the cyclic guanosine monophosphate-adenosine monophosphate synthase （cGAS）/stimulator of interferon genes （STING） signaling pathway to influence immunoinflammation. MethodsSixty SD rats were randomly divided into a blank group， a model group， a suvorexant group （30 mg·kg^-1）， and Anmeidan low-， medium-， and high-dose groups （4.55， 9.09， and 18.18 g·kg^-1）， with 10 rats in each group. The insomnia rat model was induced by intraperitoneal injection of p-chlorophenylalanine （PCPA）. Anmeidan decoction and normal saline were administered by gavage for 28 days at the corresponding doses. Morris water maze and new object recognition tests were used to assess learning and memory functions. Hematoxylin-eosin （HE） staining and Nissl staining were performed to observe hippocampal cell morphology. Enzyme-linked immunosorbent assay （ELISA） was used to measure the serum levels of interleukin-1 （IL-1）， interleukin-1β （IL-1β）， interleukin-6 （IL-6）， interleukin-8 （IL-8）， interleukin-12 （IL-12）， interleukin-18 （IL-18）， and tumor necrosis factor-α （TNF-α）. Western blot and Real-time quantitative polymerase chain reaction（Real-time PCR） were used to detect the relative protein and mRNA expression levels of hippocampal cGAS and STING. ResultsCompared with the blank group， the 5-HT content in the model group was significantly reduced （P<0.01）. The latency to the upper platform and total distance were significantly increased （P<0.05， P<0.01）， while the residence time in the target quadrant and the number of platform crossings were significantly reduced （P<0.01）， and the relative recognition index for new objects was significantly lower （P<0.01）. The morphology and arrangement of hippocampal neurons were loose and disordered， with a decreased number of intracellular Nissl bodies. The relative expression levels of IL-1， IL-1β， IL-6， IL-8， IL-12， IL-18， TNF-α， cGAS， and STING pathway proteins and mRNA were significantly upregulated （P<0.01）. Compared with the model group， the latency to the upper platform in the high-dose Anmeidan group was significantly shortened （P<0.05）. In the medium- and high-dose Anmeidan groups and the suvorexant group， the residence time in the target quadrant and the number of platform crossings were significantly increased （P<0.01）. The total distance traveled was significantly reduced （P<0.01）， and the relative recognition index for new objects was significantly increased （P<0.01）. The hippocampal neurons were more neatly arranged， and the number of intracellular Nissl bodies increased. The expression of IL-1， IL-1β， IL-6， IL-8， IL-12， IL-18， TNF-α， and cGAS proteins and mRNA in the medium- and high-dose Anmeidan groups was significantly downregulated （P<0.05， P<0.01）. ConclusionAnmeidan improves learning and memory in insomnia rats， possibly by suppressing immunoinflammation through inhibition of the cGAS/STING signaling pathway.

ObjectiveTo investigate the differences in efficacy and endogenous metabolic mechanisms of Anmeidan with combined use of raw and fried Ziziphi Spinosae Semen and its disassembled prescriptions in treating anxiety and cognitive impairment in insomnia rats. MethodsSixty rats were randomly divided into six groups （n=10 per group）： blank group， model group， suvorexant group （30 mg·kg^-1）， Anmeidan group （9.09 g·kg^-1）， Anmeidan with absence of raw Ziziphi Spinosae Semen group （7.38 g·kg^-1）， and Anmeidan with absence of fried Ziziphi Spinosae Semen group （7.38 g·kg^-1）. An insomnia model was constructed by intraperitoneal injection of para-chlorophenylalanine （PCPA）， followed by gavage administration of Anmeidan or its disassembled prescriptions. Anxiety levels were assessed using the open field test， while cognitive ability was evaluated via the novel object recognition test. The pathological morphology of hippocampal neurons was examined using electron microscopy. Serum samples were analyzed by ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry （UPLC-Q-TOF-MS） for principal component analysis， metabolic profiling， identification of differential metabolites， and metabolic pathway analysis. ResultsCompared with the blank group， the model group exhibited significantly increased exercise mileage， exercise time， and the ratio of the number of entries into the peripheral zone to the total number of entries into both the peripheral and central zones exhibited a marked increase （P<0.05， P<0.01）， while the novel object recognition index significantly decreased （P<0.05）. Compared with the model group， the Anmeidan and suvorexant groups showed significantly reduced exercise mileage and exercise time （P<0.01）. The ratio of the number of entries into the peripheral zone to the total number of entries into both the peripheral and central zones decreased （P<0.05）， and a significant increase in the novel object recognition index （P<0.01）. However， the disassembled prescription groups showed no significant improvement in open field test and novel object recognition test indices. Electron microscopy revealed that the Anmeidan group improved the pathological morphology of hippocampal neurons in insomnia rats. Metabolomics analysis identified 10 potential differential metabolites associated with Anmeidan's therapeutic effects， involving metabolic pathways related to phenylalanine and tryptophan biosynthesis and metabolism， as well as the serotonergic pathway. ConclusionThe combined use of raw and fried Ziziphi Spinosae Semen in Anmeidan is more effective than its disassembled prescriptions in alleviating anxiety and cognitive impairment in PCPA-induced insomnia rats. The underlying mechanism may be associated with metabolic pathways related to phenylalanine， tryptophan， and serotonin.