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 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 investigate HER2 mRNA expression in breast cancer with HER2 immunohistochemistry (IHC) 0 and to analyze the feasibility of distinguishing between the tumor with HER2 μltra-low expression and the one without expression of HER2 (no staining by IHC) by HER2 mRNA level preliminarily.Methods:HER2 mRNA was analyzed by reverse transcription digital PCR in 41 cases of formalin-fixed paraffin-embedded surgical tissue samples of invasive breast cancer obtained between January 2020 and March 2023 at Peking Union Medical College Hospital. The cohort included 21 HER2 IHC 1+ and 20 IHC 0 (12 ultra-low and 8 non-expression of HER2). HER2 mRNA expression level was quantitatively evaluated by the FAM (HER2)/VIC (reference gene) ratio.Results:The expression of HER2 mRNA for the cases with 1+, ultra-low, and non-expression of HER2 by IHC was 0.30 to 1.78 (average 0.90, median 0.82), 0.55 to 1.51 (average 0.93, median 0.90) and 0.22 to 0.78 (average 0.41, median 0.36), respectively. For the mean and median HER2 mRNA levels, there was no significant difference between HER2 IHC 1+ and HER2 ultra-low expression diseases ( P=0.757). A remarkable difference in HER2 gene expression was found between the tumors with 1+ and non-expression of HER2 by IHC ( P=0.002). And, HER2 ultra-low cases contained statistically higher levels of HER2 mRNA compared with non-expression of HER2 subgroup by IHC ( P=0.001). Conclusions:Based on HER2 mRNA, HER2 non-expression and HER2 weak expression (including HER2 IHC 1+ and ultra-low) belong to two different types of the tumor and the disease with HER2 IHC 1+ and HER2 ultra-low expression may be the same. It is necessary to further test the performance of HER2 mRNA detection for stratifying the HER2 weak expression subgroup and to determine the threshold.

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 investigate the impacts of periodontal-orthodontic treatment on periodontal indicators,bone metabolism and serum levels of soluble intercellular adhesion molecule-1(sICAM-1)and monocyte chemotactic protein-1(MCP-1)in patients with an-terior tooth displacement(ATD)caused by periodontitis.Methods:60 patients with ATD caused by periodontitis were included and randomly divided into a reference group(n=30,periodontal basic treatment+periodontal splint treatment)and a study group(n=30,combination of orthodontic treatment with the reference treatment).31 ATD patients who only received periodontal basic treatment were included into the blank control group.The probing depth(PD),plaque index(PLI)and gingival index(GI),tooth looseness,bone me-tabolism indicators osteocalcin(OCN)and osteoprotegerin(OPG),and serum inflammatory indicators(sICAM-1 and MCP-1)were compared among the 3 groups before and after treatment.Results:After 6 months of treatment,the levels of PD,PLI,GI,and serum sICAM-1 and MCP-1 in the 3 groups were lower than those before treatment(P＜0.05),and lower in the study group than in the refer-ence group and blank control group(P＜0.05);the looseness of the affected teeth in the 3 groups was decreased(P＜0.05),and in the study group was less than in the reference group and blank control group(P＜0.05);the levels of OCN and OPG in the 3 groups were higher(P＜0.05)than those before treatment,and in the study group were higher than in the reference group and blank control group(P＜0.05).Conclusion:Periodontal-orthodontic treatment can obviously reduce the levels of inflammatory factors in serum,effectively regulate bone metabolism and improve periodontal health in patients with ATD caused by periodontitis.

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.

To achieve non-invasive detection of hemoglobin concentration,a hemoglobin concentration detection method based on support vector regression is designed.A mathematical model for non-invasive hemoglobin detection is established based on the Beer-Lambert law.After removing the noise and baseline drift from the collected photoplethysmography signals,hemoglobin concentration information is extracted,and a recursive feature elimination algorithm is used to select the extracted information and eliminate redundant features.Finally,29 key features are identified as input to construct a hemoglobin prediction model using support vector regression algorithm.Experimental validation is conducted on 249 clinical data samples(199 cases in training dataset and 50 in test dataset),resulting in a root mean square error of 1.83 g/dL between predicted values and references,with a correlation coefficient of 0.75(P<0.01),demonstrating the high consistency of the proposed method and traditional invasive detection methods.