ObjectiveTo investigate the clinical efficacy and safety of state-target formula Angelica and Safflower spot removal essence in the treatment of melasma. MethodsA randomized，double-blind，placebo-controlled parallel-group trial was conducted，selecting patients with Qi stagnation and blood stasis type of melasma who visited the dermatology outpatient department of Beijing Hospital of Integrated Traditional Chinese and Western Medicine from September 2022 to February 2023. In accordance with the double-blind principle，a random number table was generated to randomly divide the patients into an experimental group （50 cases） and a control group （50 cases）. The experimental group applied the Angelica and Safflower spot removal essence topically，while the control group applied a placebo topically，with continuous treatment for 8 weeks and a follow-up of 1 month. Melasma Area and Severity Index （MASI），Physician Global Assessment （PGA），patient self-assessment scoring，VISIA detection and scoring were performed before medication and on the first day after stopping medication，and all adverse events were recorded. ResultsIn a study involving 100 patients，87 cases were included in the analysis. The experimental group consisted of 45 cases，with 5 dropouts，and the control group had 42 cases，with 8 dropouts. The baseline data of the patients in both groups were consistent，with no statistically significant differences. After treatment，the total effective rate of the experimental group was 75.56% （34/45），significantly higher than the control group's 2.38% （1/42），and the difference was statistically significant （χ²=48.38，P<0.01）. Compared with before treatment，after treatment，the MASI score，VISIA image spot，brown spot，and red area score of the experimental group patients were significantly reduced （P<0.05，P<0.01），while there was no statistically significant difference in the control group patients. Compared with the control group after treatment，the experimental group showed more significant improvement （P<0.05，P<0.01）. VISIA image analysis showed that after 8 weeks of treatment，the experimental group showed significant improvement in surface spots，deep spots，and red areas，while the control group remained unchanged or showed an increasing trend. 42.22% （19/45） of the experimental group had a PGA score of 3 or below，while 88.89% （40/45） had a PGA score of 4 or below. 80.95% （34/42） of the control group had a PGA score of 5 or above，and the difference between the two groups was statistically significant （χ²=38.26，P<0.01）. There was no statistically significant difference in the recurrence rate and adverse reaction rate within one month between the experimental group and the control group. ConclusionThe state-target formula Angelica and Safflower spot removal essence is clinically effective and safe in the treatment of melasma.

ObjectiveTo investigate the status and dietary intake risk of pesticide residues in fruits and vegetables sold in Wenzhou, Zhejiang Province from 2020 to 2023, so as to provide a scientific basis for the regulation and management of pesticide in the future. MethodsIn accordance with the requirements and methods specified in the “National Food Contamination and Hazardous Factor Risk Monitoring Work Manual” and the current corresponding national food inspection standards for various foods, a total of 807 samples of vegetables and fruits from various counties and districts of Wenzhou City were collected for testing and analysis. Eventually, 23 types of pesticides with a detection rate greater than 5% and those exceeding the standard were selected for dietary intake risk assessment. ResultsFrom 2020 to 2023, the overall detection rate of pesticide residues in fruits and vegetables monitored in Wenzhou was 71.62%, with an overall exceedance rate of 5.27%. From the results of the monitoring of pesticide residues in fruits and vegetables, fresh legume vegetables had the highest detection rate of 90.00%. Among the six major categories of pesticides monitored, fungicides in vegetables and fruits had the highest detection rates of 68.18% and 85.03%, respectively. The highest exceedance rate in vegetables was organophosphorus pesticides, accounting for 2.85%, while in fruits, neonicotinoid pesticides had the highest exceedance rate of 3.21%. From the perspective of sampling time, the peak detection rate of pesticide residues in fruits and vegetables in Wenzhou occurred in June and October. The index of food safety (IFS) of the 23 pesticides with a detection rate higher than 5% ranged from 0.000 7 to 0.694 2 based on the 95% monitoring value of pesticide residues, which were all less than 1. Calculated at maximum content, the IFS values of dithiocarbamate (calculated by CS₂), chlorothalonil and propiconazole were all greater than 1, indicating that the maximum detection values of the three pesticides exceeded the acceptable safety risk. The risk level of acute dietary intake of the 23 pesticides ranged from 1.26% to 52.65%. ConclusionThe overall situation of pesticide residues in fruits and vegetables sold in Wenzhou from 2020 to 2023 is favourable, but the exceedance rate of pesticide in some fruits and vegetables is high. Special attention should be paid to the pesticide residues of fungicides, neonicotinoid insecticides and organophosphorus pesticides in fresh legume vegetables, bulb vegetables and some fruits sold in Wenzhou, such as acetamiprid in bayberry and cowpea, dimethomorph in strawberry, chlorpyrifos in leek, etc., and monitoring of pesticide residues in food need to be strengthened.

ObjectiveTo obtain the gene sequences of major histocompatibility complex (MHC ) Ⅱgenes of Wuzhishan pigs, analyze their genetic information, and explore the biological functions of their MHC system. MethodsSpleen samples were collected from 3 adult male Wuzhishan pigs. Primers were designed according to MHCⅡ gene sequences, and the coding sequences of Wuzhishan pig MHCⅡ genes were amplified by RT-PCR. Sanger sequencing was performed to determine the full-length sequences. Bioinformatics tools were employed to analyze the physicochemical properties, phylogenetic relationships, conserved motifs, structural domains, chromosomal localization, and syntenic relationships of these genes. ResultsEight MHCⅡ genes were identified in Wuzhishan pigs, designated as SLA-DRA, SLA-DQA, SLA-DQB, SLA-DRB, SLA-DOB, SLA-DMB, SLA-DMA and SLA-DOA. The full-length sequences of these genes were determined by Sanger sequencing and subsequently deposited in GenBank under accession numbers PQ182796, PQ182797, PQ182798, PQ182799, PQ182800, PQ182801, PQ182802, and PQ164779. Phylogenetic analysis showed that the six MHCⅡ genes of Wuzhishan pigs clustered separately from their counterparts in Duroc, Meishan, Large White, and Bama pigs, indicating distinct evolutionary trajectories. Bioinformatics analysis demonstrated that most MHC Ⅱ proteins were hydrophobic, with molecular weights ranging from 27 700 to 30 000 Da. Genes within the same subregion shared conserved motifs. Specifically, four MHCⅡ proteins encoded by SLA-DQB, SLA-DRB, SLA-DOB, and SLA-DMB contained the MHCⅡβ conserved domain, while those encoded by the genes SLA-DRA, SLA-DQA, SLA-DMA, and SLA-DOA contained the MHCⅡα conserved domain. The eight MHCⅡ genes were scattered along the long arm of chromosome 7 in the Wuzhishan pigs, exhibiting syntenic relationships with three human genes and five Duroc pig genes. ConclusionThe MHCⅡ genes of Wuzhishan pigs may possess a unique evolutionary origin.

ObjectiveTo obtain the gene sequences of major histocompatibility complex (MHC ) Ⅱgenes of Wuzhishan pigs, analyze their genetic information, and explore the biological functions of their MHC system. MethodsSpleen samples were collected from 3 adult male Wuzhishan pigs. Primers were designed according to MHCⅡ gene sequences, and the coding sequences of Wuzhishan pig MHCⅡ genes were amplified by RT-PCR. Sanger sequencing was performed to determine the full-length sequences. Bioinformatics tools were employed to analyze the physicochemical properties, phylogenetic relationships, conserved motifs, structural domains, chromosomal localization, and syntenic relationships of these genes. ResultsEight MHCⅡ genes were identified in Wuzhishan pigs, designated as SLA-DRA, SLA-DQA, SLA-DQB, SLA-DRB, SLA-DOB, SLA-DMB, SLA-DMA and SLA-DOA. The full-length sequences of these genes were determined by Sanger sequencing and subsequently deposited in GenBank under accession numbers PQ182796, PQ182797, PQ182798, PQ182799, PQ182800, PQ182801, PQ182802, and PQ164779. Phylogenetic analysis showed that the six MHCⅡ genes of Wuzhishan pigs clustered separately from their counterparts in Duroc, Meishan, Large White, and Bama pigs, indicating distinct evolutionary trajectories. Bioinformatics analysis demonstrated that most MHC Ⅱ proteins were hydrophobic, with molecular weights ranging from 27 700 to 30 000 Da. Genes within the same subregion shared conserved motifs. Specifically, four MHCⅡ proteins encoded by SLA-DQB, SLA-DRB, SLA-DOB, and SLA-DMB contained the MHCⅡβ conserved domain, while those encoded by the genes SLA-DRA, SLA-DQA, SLA-DMA, and SLA-DOA contained the MHCⅡα conserved domain. The eight MHCⅡ genes were scattered along the long arm of chromosome 7 in the Wuzhishan pigs, exhibiting syntenic relationships with three human genes and five Duroc pig genes. ConclusionThe MHCⅡ genes of Wuzhishan pigs may possess a unique evolutionary origin.

Objective : To explore the effect of esketamine on anxiety-depressive-like behavior in mice and its rela- tionship with inflammation． Methods : SPF grade healthy adult male C57BL/6J mice，weighing 20 －24 g，were used in the exprement．The random number table method was used to divide into 5 groups (n = 8) : control group ( Con group) ，esketamine group (ESK group) ，model group ( LPS group) ，model + esketamine prevention group (LPS + ESK1 group) and model + esketamine treatment group ( LPS + ESK2 group) ．An inflammation-induced anxiety-depression model was prepared by intraperitoneal injection of LPS 0. 83 mg / kg．The ESK group was injec- ted with esketamine 10 mg / kg ; LPS group was injected with LPS 0. 83 mg / kg ; LPS + ESK1 group was injected with LPS 0. 83 mg / kg before 24 hours intraperitoneal injection of esketamine 10 mg / kg ; and the LPS + ESK2 group was injected with LPS 0. 83 mg / kg and 30 minutes later with esketamine 10 mg / kg．24 h after intraperitoneal injec- tion of LPS，the anxiety-depression-like behaviors of mice were measured using behavioral experiments．At the end of behavioral experiments，the spleen was taken immediately ; hippocampal tissues were taken and enzyme-linked immunosorbent assay (ELISA) was used to detect the contents of interleukin-1 β (IL-1 β) ，tumor necrosis factor al- pha (TNF-α) and interleukin 6 (IL-6) and neuronal pathological changes in hippocampal tissues were observed by HE staining. Results : Compared with the Con group，mice in the LPS group showed increased anxiety and depres- sion-like behavior (P＜0. 05) ，increased spleen weight / body weight (P ＜0. 05 ) ，increased hippocampal tissue concentrations of IL-1 β , TNF-α and IL-6 (P＜0. 05) ，and increased neuronal degeneration necrosis，there was no statistically significant difference in these indicators in the ESK group compared with the Con group．Compared with the LPS group，mice in the LPS + ESK1 and LPS + ESK2 groups showed reduced anxiety-depression-like behavior (P＜0. 05) ，decreased splenic weight / body weight (P ＜0. 05) ，hippocampal tissue IL-1 β , TNF-α , IL- 6 con- centrations were reduced (P＜0. 05) ，and neuronal degeneration necrosis was reduced．Compared with the LPS + ESK1 group，the LPS + ESK2 group showed an increase in the distance travelled in the central area of the open field experiment and the distance into the open arm of the elevated cross maze experiment (P＜0. 05) ，a decrease in IL-6 and TNF-α concentrations (P＜0. 05) ，and a reduction in the degree of neuronal damage． Conclusion Esketamine ameliorates LPS-induced anxiety-depression-like behavior and neuronal damage in mice by a mechanism that may be related to reduced inflammation.

Objective:To analyze the clinical characteristics and prognosis of patients with infant acute lymphoblastic leukemia (IALL).Methods:A retrospective cohort study.Clinical data, treatment and prognosis of 28 cases of IALL who have been treated at Beijing Children′s Hospital, Capital Medical University and Baoding Children′s Hospital from October 2013 to May 2023 were analyzed retrospectively. Based on the results of fluorescence in situ hybridization (FISH), all patients were divided into KMT2A gene rearrangement (KMT2A-R) positive group and KMT2A-R negative group. The prognosis of two groups were compared. Kaplan-Meier method and Log-Rank test were used to analyze the survival of the patients.Results:Among 28 cases of IALL, there were 10 males and 18 females, with the onset age of 10.9 (9.4,11.8) months. In terms of immune classification, 25 cases were B-ALL (89%), while the remaining 3 cases were T-ALL (11%). Most infant B-ALL showed pro-B lymphocyte phenotype (16/25,64%). A total of 22 cases (79%) obtained chromosome karyotype results, of which 7 were normal karyotypes, no complex karyotypes and 15 were abnormal karyotypes were found. Among abnormal karyotypes, there were 4 cases of t (9; 11), 2 cases of t (4; 11), 2 cases of t (11; 19), 1 case of t (1; 11) and 6 cases of other abnormal karyotypes. A total of 19 cases (68%) were positive for KMT2A-R detected by FISH. The KMT2A fusion gene was detected by real-time PCR in 16 cases (57%). A total of 24 patients completed standardized induction chemotherapy and were able to undergo efficacy evaluation, 23 cases (96%) achieved complete remission through induction chemotherapy, 4 cases (17%) died of relapse. The 5-year event free survival rate (EFS) was (46±13)%, and the 5-year overall survival rate (OS) was (73±10)%.The survival time was 31.3 (3.3, 62.5) months. There was no significant statistical difference in 5-year EFS ((46±14)% vs. (61±18)%) and 5-year OS ((64±13)% vs. (86±13)%) between the KMT2A-R positive group (15 cases) and the KMT2A-R negative group (9 cases) ( χ2=1.88, 1.47, P=0.170, 0.224). Conclusions:Most IALL patients were accompanied by KMT2A-R. They had poor tolerance to traditional chemotherapy, the relapse rate during treatment was high and the prognosis was poor.

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 analyze the domestic antibody drug safety and risk research status,the latest research hotspots and frontiers in the current ten years.Methods CiteSpace 6.2.R2 software was used to analyze all literature related to the safety and risk of antibody drugs in CNKI,WanFang data and Vip database from 2012 to 2022.Results A total of 2 773 pieces of literature were obtained from the three databases,which were imported into CiteSpace after deduplication,and finally,1 870 pieces were included in the analysis.In the past decade,the number of articles published in the field of antibody drugs safety and risk research has remained at about 100 articles per year from 2012 to 2019,since 2020,the number of articles published has started to increase,and the annual number of articles published has increased to around 300 articles from 2021 to 2022.The network graph of domestic institutional cooperation showed that there was a lack of cooperation among the research institutions of antibody drug safety and risk research,mainly due to the fact that hospitals were conducting research in this field,and the types of research subjects were relatively single.The author collaboration network graph showed that the core teams in this research field,such as Li Bo,Yang Yanwei,and Lin Zhi,had the closest collaboration,while there was less collaboration among high-yield authors,additionally,some experts and scholars conducted research on their own as individuals or small groups,the research focused on adverse reactions,safety,bevacizumab,Rituximab,Meta-analysis,etc.Conclusion In the past decade,domestic research has mainly focused on the clinical efficacy and safety of antibody drugs,with few scholars exploring the risk of antibody drugs,therefore,in the future,it is necessary to pay attention to the research on the risks of antibody drugs.

Recent trends suggest that Chinese herbal medicine formulas(CHM formulas)are promising treatments for complex diseases.To characterize the precise syndromes,precise diseases and precise targets of the precise targets between complex diseases and CHM formulas,we developed an artificial intelligence-based quantitative predictive algorithm(DeepTCM).DeepTCM has gone through multilevel model cali-bration and validation against a comprehensive set of herb and disease data so that it accurately captures the complex cellular signaling,molecular and theoretical levels of traditional Chinese medicine(TCM).As an example,our model simulated the optimal CHM formulas for the treatment of coronary heart disease(CHD)with depression,and through model sensitivity analysis,we calculated the balanced scoring of the formulas.Furthermore,we constructed a biological knowledge graph representing interactions by associating herb-target and gene-disease interactions.Finally,we experimentally confirmed the thera-peutic effect and pharmacological mechanism of a novel model-predicted intervention in humans and mice.This novel multiscale model opened up a new avenue to combine"disease syndrome"and"macro micro"system modeling to facilitate translational research in CHM formulas.

Objective:To analyze the association between the rs562556 polymorphism of the proprotein convertase subtilisin/kexin type 9(PCSK9)gene and the degree of coronary artery stenosis in the patients with acute myocardial infarction(AMI).Methods:A total of 200 patients diagnosed with AMI from January 2021 to December 2022 were selected as AMI group,and 200 healthy individuals during the same period were selected as control group.According to the Gensini scoring standard,the patients in AMI group were divided into low risk group(Gensini score≤40,n=78)and medium-high risk group(Gensini score>40,n=122).The levels of lipid metabolism indicators in serum of the patients in two groups were detected by fully automatic biochemical analyzer;enzyme linked immunosorbent assay(ELISA)method was used to detect the PCSK9 levels in serum of the patients in two groups;ultraviolet spectrophotometry was used to detect the single nucleotide polymorphism(SNP)of PCSK9 gene of the patients in two groups;Spearman correlation analysis was used to detect the correlation between the rs562556 polymorphism of the PCSK9 gene and the degree of the disease and the levels of lipid metabolism indicators in serum of the patients.Results:Compared with control group,the percentage of smokers of the patients in AMI group was significantly increased(P<0.01).Compared with control group,the levels of low-density lipoprotein cholesterol(LDL-c)and PCSK9 in serum of the patients in AMI group were significantly increased(P<0.05).Compared with low risk group,the levels of LDL-c and PCSK9 in serum of the patients in medium-high risk group were significantly increased(P<0.05).The distribution of PCSK9 gene rs1800487 genotype in both control and AMI groups conformed to the Hardy-Weinberg(H-W)equilibrium(χ2=0.677,P=0.713;χ2=0.970,P=0.831).Compared with control group,the distribution frequencies of PCSK9 gene rs562556 genotype AA and allele A of the patients in AMI group were significantly increased(P<0.05).In the AMI patients,the distribution of PCSK9 gene rs562556 genotype in both low risk and medium-high risk groups conformed to the H-W equilibrium(χ2=0.045,P=0.978;χ2=1.290,P=0.525).Compared with low risk group,the distribution frequencies of genotype AA and allele A of PCSK9 gene rs562556 of the patients in medium-high risk group were significantly increased(P<0.05).The PCSK9 gene rs562556 genotype AA was positively correlated with the degree of AMI(r=0.193,P=0.006)and LDL-c level(r=0.301,P<0.01).Allele A was positively correlated with the LDL-c level(r=0.168,P=0.017).Conclusion:The PCSK9 gene rs562556 genotype AA is positively correlated with the degree of coronary artery stenosis of the AMI patients,and its polymorphism may promote the development of AMI by upregulating the LDL-c level.