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.

Objective:To introduce the clinical application of "page-turning" superior pancreatic lymph node dissection in laparoscopic D2 radical gastrectomy for gastric cancer.Methods:Patients who were confirmed to have adenocarcinoma by preoperative gastroscopy and pathological biopsy, with tumor staging evaluated by imaging as cT1~4aN0~3M0, without neoadjuvant therapy, and without absolute surgical contraindications, underwent laparoscopic radical gastrectomy for gastric cancer with "page-turning" superior pancreatic lymph node dissection. The "page-turning" superior pancreatic lymph node dissection was performed in four steps: (1) Expose the posterior gastric mesentery and dissect No.11p lymph nodes; (2) Expose the left gastric mesentery and dissect No.7, No.8a and No.9 lymph nodes; (3) Expose the right gastric mesentery and dissect No.5 lymph nodes; (4) Expose the left edge of the portal vein and dissect No.12a lymph nodes.Results:From April 2018 to October 2024, 112 patients with gastric cancer underwent laparoscopic D2 radical gastrectomy with "page-turning" superior pancreatic lymph node dissection, including 21 cases in the First Affiliated Hospital of Guangzhou University of Chinese Medicine, 78 cases in the Second Affiliated Hospital of Guangzhou University of Chinese Medicine, and 13 cases in the Department of Gastrointestinal Surgery, Jilin Provincial People's Hospital. The TNM staging of all patients was as follows: 31 cases in stage Ⅰ, 24 cases in stage Ⅱ, and 57 cases in stage Ⅲ; 62 cases of differentiated adenocarcinoma and 50 cases of undifferentiated adenocarcinoma; the median length of tumors was 3.8 cm. All patients successfully completed the operation without conversion to open surgery, no intraoperative massive hemorrhage or postoperative death. The median total number of lymph nodes dissected in all patients was 32, and the median number of positive lymph nodes was 4.5. The overall postoperative complication rate was 5.4% (6/112), all of which were Clavien-Dindo grade Ⅱ, including pulmonary infection, pleural effusion, and incisional infection, all cured by symptomatic treatment. The median follow-up was 41.8 (2-78) months, with 7 cases lost to follow-up. During the follow-up period, 27 cases (25.7%) had tumor recurrence and 16 cases (15.2%) died.Conclusions:The "page-turning" superior pancreatic lymph node dissection technique is safe and feasible in laparoscopic radical gastrectomy for gastric cancer.

Objective:To explore the application value of integrated Chinese and western medicine in the treatment of sepsis-induced coagulopathy (SIC) induced by bacterial pneumonia sepsis.Methods:A total of 60 inpatients with bacterial pneumonia and sepsis admitted to the Dongzhimen Hospital of Beijing University of Chinese Medicine from October 2023 to June 2024 were collected in a cross-sectional study. Serum samples were collected, and immune indexes, coagulation function and some laboratory test results of the patients were detected or recorded. Sepsis Associated Sequential Organ Failure Assessment (SOFA) score and Acute Physiology and Chronic Health Evaluation Ⅱ (APACHE Ⅱ) score were evaluated.Results:Among the 60 patients, 71.7%( n=43) were associated with coagulation disorder, 65%( n=39) showed hemorrhagic SIC; A total of 37 patients (61.7%) were treated with integrated traditional Chinese and western medicine, and 23 patients (38.3%) were treated with Western medicine. The main types of syndrome differentiation were toxic-heat syndrome ( n=48, 80.0%) and blood-stasis syndrome ( n=11, 18.3%). Serum human monocyte chemoattractant protein-1 (MCP-1) and platelet count (PLT) in patients with blood stasis syndrome were significantly lower than those in toxic-heat syndrome (all P<0.05). In patients with bacterial pneumonia sepsis, the total score of syndrome of excess of fu-viscera (Fu-shi-zheng) was positively correlated with programmed death ligand-1 (PD-L1) ( r=0.293, P=0.023) and tumor necrosis factor-α (TNF-α) ( r=0.436, P=0.001). The total score of toxin-heat syndrome ( r=0.323, P=0.016) and excess of fu-viscera syndrome ( r=0.354, P=0.008) were positively correlated with prothrombin time (PT). PD-1 was positively correlated with SOFA score ( r=0.343, P=0.007) and APACHE Ⅱ score ( r=0.354, P=0.006). The PD-1 level and SOFA and APACHE Ⅱ scores of the patients treated with integrated Chinese and western medicine were significantly lower than those treated with Western medicine alone (all P<0.05). Conclusions:The combined intervention of traditional Chinese medicine and Western medicine based on " Fuzheng Touxie Jiedu (The method of strengthening the body and removing the toxin)" has strong clinical guiding significance, and can effectively improve the immune function and prognosis of bacterial pneumonia SIC.

Objective:To explore the application value of integrated Chinese and western medicine in the treatment of sepsis-induced coagulopathy (SIC) induced by bacterial pneumonia sepsis.Methods:A total of 60 inpatients with bacterial pneumonia and sepsis admitted to the Dongzhimen Hospital of Beijing University of Chinese Medicine from October 2023 to June 2024 were collected in a cross-sectional study. Serum samples were collected, and immune indexes, coagulation function and some laboratory test results of the patients were detected or recorded. Sepsis Associated Sequential Organ Failure Assessment (SOFA) score and Acute Physiology and Chronic Health Evaluation Ⅱ (APACHE Ⅱ) score were evaluated.Results:Among the 60 patients, 71.7%( n=43) were associated with coagulation disorder, 65%( n=39) showed hemorrhagic SIC; A total of 37 patients (61.7%) were treated with integrated traditional Chinese and western medicine, and 23 patients (38.3%) were treated with Western medicine. The main types of syndrome differentiation were toxic-heat syndrome ( n=48, 80.0%) and blood-stasis syndrome ( n=11, 18.3%). Serum human monocyte chemoattractant protein-1 (MCP-1) and platelet count (PLT) in patients with blood stasis syndrome were significantly lower than those in toxic-heat syndrome (all P<0.05). In patients with bacterial pneumonia sepsis, the total score of syndrome of excess of fu-viscera (Fu-shi-zheng) was positively correlated with programmed death ligand-1 (PD-L1) ( r=0.293, P=0.023) and tumor necrosis factor-α (TNF-α) ( r=0.436, P=0.001). The total score of toxin-heat syndrome ( r=0.323, P=0.016) and excess of fu-viscera syndrome ( r=0.354, P=0.008) were positively correlated with prothrombin time (PT). PD-1 was positively correlated with SOFA score ( r=0.343, P=0.007) and APACHE Ⅱ score ( r=0.354, P=0.006). The PD-1 level and SOFA and APACHE Ⅱ scores of the patients treated with integrated Chinese and western medicine were significantly lower than those treated with Western medicine alone (all P<0.05). Conclusions:The combined intervention of traditional Chinese medicine and Western medicine based on " Fuzheng Touxie Jiedu (The method of strengthening the body and removing the toxin)" has strong clinical guiding significance, and can effectively improve the immune function and prognosis of bacterial pneumonia SIC.

Objective:To introduce the clinical application of "page-turning" superior pancreatic lymph node dissection in laparoscopic D2 radical gastrectomy for gastric cancer.Methods:Patients who were confirmed to have adenocarcinoma by preoperative gastroscopy and pathological biopsy, with tumor staging evaluated by imaging as cT1~4aN0~3M0, without neoadjuvant therapy, and without absolute surgical contraindications, underwent laparoscopic radical gastrectomy for gastric cancer with "page-turning" superior pancreatic lymph node dissection. The "page-turning" superior pancreatic lymph node dissection was performed in four steps: (1) Expose the posterior gastric mesentery and dissect No.11p lymph nodes; (2) Expose the left gastric mesentery and dissect No.7, No.8a and No.9 lymph nodes; (3) Expose the right gastric mesentery and dissect No.5 lymph nodes; (4) Expose the left edge of the portal vein and dissect No.12a lymph nodes.Results:From April 2018 to October 2024, 112 patients with gastric cancer underwent laparoscopic D2 radical gastrectomy with "page-turning" superior pancreatic lymph node dissection, including 21 cases in the First Affiliated Hospital of Guangzhou University of Chinese Medicine, 78 cases in the Second Affiliated Hospital of Guangzhou University of Chinese Medicine, and 13 cases in the Department of Gastrointestinal Surgery, Jilin Provincial People's Hospital. The TNM staging of all patients was as follows: 31 cases in stage Ⅰ, 24 cases in stage Ⅱ, and 57 cases in stage Ⅲ; 62 cases of differentiated adenocarcinoma and 50 cases of undifferentiated adenocarcinoma; the median length of tumors was 3.8 cm. All patients successfully completed the operation without conversion to open surgery, no intraoperative massive hemorrhage or postoperative death. The median total number of lymph nodes dissected in all patients was 32, and the median number of positive lymph nodes was 4.5. The overall postoperative complication rate was 5.4% (6/112), all of which were Clavien-Dindo grade Ⅱ, including pulmonary infection, pleural effusion, and incisional infection, all cured by symptomatic treatment. The median follow-up was 41.8 (2-78) months, with 7 cases lost to follow-up. During the follow-up period, 27 cases (25.7%) had tumor recurrence and 16 cases (15.2%) died.Conclusions:The "page-turning" superior pancreatic lymph node dissection technique is safe and feasible in laparoscopic radical gastrectomy for gastric cancer.

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.

Objective To explore the diagnosis of clinically suspicious von Willebrand disease(vWD)in a family and its pathogene-sis.Methods The pedigree information and the biological specimen were collected from the clinically suspected VWD patient and her family members(4 persons in total)in Peking University First Hospital.The levels of platelet count(PLT),activated partial thrombo-plastin time(APTT),vWF antigen(vWF:Ag),vWF activity(vWF:Ac)and FⅧ activity(FⅧ:C)were detected,and vWF risto-cetin cofactor(vWF:RCo)assay,ristocetin-induced platelet aggregation assay(RIPA)and vWF collagen binding(vWF:CB)assay were performed for phenotype diagnosis.The peripheral blood genomic DNAs were extracted from the proband and her family members to perform whole-exome sequencing for identifying the mutation of vWF gene,The mutation site was analyzed by using bioinformation tools to explore the pathogenesis of the proband.Results The APTT of proband(m 1)was slightly prolonged and her vWF:Ag,vWF:Ac,vWF:RCo and vWF:CB were significantly decreased.There was no obvious aggregation in RIPA assay(1.0 mg/mL and 1.25 mg/mL).In her father(Ⅱ3),APTT,FⅧ:C,vWF:Ag,vWF:Ac and vWF:CB were normal,but vWF:RCo was slightly decreased.In her mother(Ⅱ4),APTT,FⅧ:C,vWF:Ag,vWF:RCo and vWF:CB were all normal,but vWF:Ac significantly decreased.In her brother(Ⅲ2),APTT and FⅧ:C were normal,but vWF:Ag,vWF:Ac,vWF:RCo and vWF:CB were reduced to varying degrees.In all the family members(father,mother and brpther),no apparent aggregation in RIPA(1.0 mg/mL)was shown.Genetic analysis showed that the proband(Ⅲ1)carried a compound heterozygous mutation of vWF gene c.7288-9T＞G and c.1117C＞T,her father(Ⅱ3)carried vWF gene c.7288-9T＞G heterozygous mutation,and vWF gene c.1117C＞T heterozygous mutation was presented in both mother(Ⅱ4)and brother(Ⅲ2).Conclusion According to the results of laboratory tests,the proband was diagnosed as type 2A vWD.The hetero-zygous mutation in vWF gene c.1117C＞T and c.7288-9T＞G may be the molecular mechanism leading to type 2A vWD in the proband.

Objective To explore the correlations between serum Mas-related G protein-coupled receptor X2 (MRGPRX2), interleukin (IL)-4, IL-5, IL-6, IL-13, IL-23 and IL-33 levels and chronic spontaneous urticaria (CSU). Methods The clinical characteristics and laboratory data from 55 patients with CSU and 21 healthy controls at Huashan Hospital, Fudan University from February 2021 to September 2023 were collected. The disease activity and severity of CSU patients were assessed. Serum level of MRGPRX2 was tested using enzyme-linked immunosorbent assay (ELISA), and levels of IL-4, IL-5, IL-6, IL-13, IL-23, and IL-33 were measured using Luminex multiplex assay in all subjects. Spearman correlation analysis was used to evaluate the correlations between biomarkers and other parameters in CSU patients, and logistic regression analysis was performed to identify factors influencing CSU. Results CSU patients exhibited significantly higher serum levels of MRGPRX2 (2.41[0, 11.51] ng/mL vs 0[0, 2.86] ng/mL, P＝0.015) and IL-23 (0.09[0.04, 0.56] pg/mL vs 0.05[0.03, 0.08] pg/mL, P＝0.033) than healthy controls. There was no difference in levels of other cytokines between the two groups. There was no difference in levels of MRGPRX2 and cytokines between severe and non-severe CSU patients. Correlation analysis showed that serum MRGPRX2 levels in CSU patients were positively correlated with IL-4 (r＝0.345, P＝0.010) and IL-6 (r＝0.395, P＝0.003) levels. Logistic regression analysis indicated that MRGPRX2≥0.055 ng/mL and IL-23≥0.135 pg/mL were independent risk factors for CSU (P＜0.05). Conclusions Serum levels of MRGPRX2 and IL-23 in CSU patients are elevated, which may be involved in the pathogenesis of CSU.

In 2009,the World Health Organization included snakebite on the list of neglected tropical diseases,acknowledging it as a common occupational hazard for farmers,plantation workers,and others,causing tens of thousands of deaths and chronic physical disabilities every year.This guideline aims to provide practical information to help clinical professionals evaluate and treat snakebite victims.These recommendations are based on clinical experience and clinical research evidence.This guideline focuses on the following topics:snake venom,clinical manifestations,auxiliary examination,diagnosis,treatments,and prevention.