Objective:To explore the mechanism of Honghua Xiaoyao Tablets in the treatment of premature ovarian failure (POF) using network pharmacology and molecular docking technology; To conduct further experimental verification.Methods:The active components and related targets of Honghua Xiaoyao Tablets were obtained using TCMSP and PubChem databases, and the related targets of POF were obtained by using GeneCards database. The Venn online tool was used to screen the intersection genes, and the STRING database was used to construct the PPI network. Then, GO function enrichment analysis and KEGG pathway enrichment analysis were performed on the intersecting genes through the Metescape database, and Cytoscape 3.7.1 software was used to construct the "active component-target" network and "Chinese materia medica-active component-target-key pathway-disease" network. Finally, molecular docking verification was carried out. Mice were divided into blank group, model group, and Honghua Xiaoyao Tablets group using a random number table method, with 8 mice in each group. Except for the blank group, mice in each group were treated with zona pellucida polypeptide 3 (ZP3) and Freund's Complete Adjuvant (FCA) to establish a mouse model of immune POF. Mice in the Honghua Xiaoyao Tablets group received Honghua Xiaoyao Tablets solution 0.56 g/kg for gavage, and the blank control group and the model group received saline for gavage for consecutive 4 weeks. The histopathological changes of the mouse ovary were observed by HE staining. Immunohistochemical staining was used to observe the expression of ESR1, and Western blot was used to detect the expressions of Akt and p-Akt.Results:A total of 80 intersection targets between Honghua Xiaoyao Tablets and POF were obtained, and the PPI network contained 44 core targets. The top 5 compounds in the topological analysis were formononetin, quercetin, Betulinic acid, Hydroxysafflor Yellow A and Baicalin, and the top 5 targets were PPARG, ESR1, AR, AKT1 and IL6. The molecular function of core genes was mainly receptor ligand activity, and its biological process mainly involved the positive regulation of cell migration. The cellular components mainly included membrane rafts, which were involved in signaling pathways such as cancer signaling pathway, proteoglycans in cancer, PI3K-Akt signaling pathway, and HIF-1 signaling pathway. "Chinese materia medica-component-target-pathway-disease" network showed that 8 kinds of Chinese materia medica in the Honghua Xiaoyao Tablets had important core components, among which Glycyrrhizae Radix et Rhizoma and Carthami Flos involved the most important core components. Molecular docking results showed that the active components had a good affinity with the core target. The experimental verification confirmed that Honghua Xiaoyao Tablets promoted follicular development, increased the expression of ESR1 in ovarian tissues and up-regulated the expression level of the key factor of Akt phosphorylation in the PI3K-Akt signaling pathway.Conclusions:The various active components of Honghua Xiaoyao Tablets may act on PPARG, ESR1 and other targets through multiple signaling pathways such as PI3K-Akt and HIF-1 to treat POF. The potential active components are mainly formononetin, quercetin, etc.

Objective:To evaluate the efficacy and safety of dupilumab in the treatment of prurigo nodularis (PN) in the real world.Methods:PN patients who were subcutaneously injected with dupilumab for over 12 weeks were collected from the China Type Ⅱ Inflammatory Skin Disease Clinical Research and Standardized Diagnosis and Treatment Project Database from June 2021 to October 2022. Their clinical data were retrospectively analyzed, which included demographic data, and changes in pruritus numeric rating scale (NRS), investigator global assessment for PN-Stage (IGA PN-S), dermatology life quality index (DLQI) and hospital anxiety and depression scale (HADS) scores before and after treatment. Differences in scores before and after treatment, as well as in efficacy between patients with and without a history of atopic diseases, were analyzed using Wilcoxon signed-rank test, paired t-test or chi-square test. Results:A total of 66 PN patients were collected, including 42 males and 24 females, and they were aged 8 to 89 (44.12 ± 24.17) years. Thirty-six patients had a history of atopic diseases, and 27 had a family history of atopic diseases. After 12-week treatment with dupilumab, the pruritus NRS, IGA PN-S and DLQI scores in the 66 patients significantly decreased from the baseline scores (7.00 [5.00, 8.00], 3.00 [3.00, 4.00], 12.00 [7.75, 20.25], respectively) to 3.00 [2.00, 4.25], 2.00 [2.00, 3.00], 5.00 [1.75, 8.25], respectively (all P < 0.001). Among the 66 patients, 39 continued the regular treatment with dupilumab after 12 weeks and were followed up to 16 weeks; their pruritus NRS and IGA PN-S scores at week 16 further decreased compared with those at week 12 (both P < 0.05). There were no significant differences in the proportion of patients showing an improvement of ≥ 4 points in the NRS score or the proportion of patients achieving IGA 0/1 at week 12 between the patients with history of atopic diseases and those without (both P > 0.05). Before treatment, 32 PN patients were accompanied by mild to severe anxiety and/or depression; after 12-week treatment, the HADS-A scores in the 28 patients with anxiety (HADS-A scores > 7 points) and the HADS-D scores in the 20 patients with depression (HADS-D scores > 7 points) significantly decreased compared with their baseline scores (both P < 0.001) ; 18 (56.52%) patients achieved remission in anxiety and depression (both HADS-A and HADS-D scores < 7 points). Among the 66 PN patients, there were 13 minor patients, including 7 males and 6 females, and they were aged 8 to 17 (13.77 ± 3.09) years; after 12-week treatment, their pruritus NRS, IGA PN-S, and DLQI scores significantly decreased compared with the corresponding baseline scores (all P < 0.05) ; 8 minor patients continued dupilumab treatment for 16 weeks, with a further decrease in the IGA PN-S score compared with that at week 12 ( P < 0.05), but without significant differences between the pruritus NRS and DLQI scores at week 16 and those at week 12 (both P > 0.05). Adverse reactions were observed in 7 adult patients, including eye pruritus, local injection reactions, and systemic erythema accompanied by pruritus on the day of injection. No adverse reactions were reported in minor patients. Conclusion:In the real world, dupilumab could markedly alleviate pruritus, skin lesions, anxiety and depression symptoms in PN, improve the quality of life, and exhibited a good safety profile.

Objective To investigate the seasonal Aedes population fluctuation and the resistance of Aedes populations to common insecticides in Jiangsu Province in 2020, so as to provide insights into vector-borne infectious diseases control.. Methods One village was randomly sampled from each of Xinbei District of Changzhou City and Zhangjiagang County of Suzhou City in southern Jiangsu Province, Hai’an County of Nantong City and Yandu District of Yancheng City in Central Jiangsu Province, and Suining County of Xuzhou City and Sihong County of Suqian City in northern Jiangsu Province during the period between May and October, 2020. A small ponding container was sampled, and larval Aedes mosquitoes were collected using straws once each in early and late stages of each month. All larvae were bred in laboratory to adults for population identification. In addition, larval breeding were observed in all small ponding containers in and out of 30 households that were randomly sampled from six surveillance sites, and the larval mosquito density was estimated using Breteau index. Larval A. albopictus mosquitoes were sampled around Cuiyuan New Village in Jintan District of Changzhou City, and bred in laboratory to the first offspring generation, and the susceptibility of adult female mosquitoes to deltamethrin, lambda-cyhalothrin, malathion, and propoxur was tested using the filter-paper bioassay recommended by WHO. Results A total of 1 165 larval Aedes mosquitoes were captured from small ponding containers in six surveillance sites of Jiangsu Province in 2020, and all were identified as A. albopictus following eclosion. The largest number of Aedes larvae captured was found in July. A total of 1 152 households were investigated in six surveillance sites, and the mean Breteau indexes were 9.58, 13.20, 13.71, 13.20, 12.18 and 5.58 from May to October, respectively, while a high Aedes transmission risk was seen in Xinbei District of Changzhou City, with a higher Breteau index than in Suining (H = 23.667, P_adjusted = 0.001) and Sihong (H = 22.500, P_adjusted = 0.003) counties. The field-captured A. albopictus from Cuiyuan New Village in Jintan District of Changzhou City remained sensitive to malathion, but was resistant to propoxur, and developed high-level resistance to deltamethrin and lambda-cyhalothrin. Conclusions A. albopictus was present in southern, central and northern Jiangsu Province in 2020, and the larval density peaked in July. A. albopictus captured from Cuiyuan New Village in Jintan District of Changzhou City has developed high-level resistance to pyrethroid pesticides.

Objective:To investigate changes in skin microecological structures and functions between acute and remission phases in adult patients with severe atopic dermatitis (AD) .Methods:From October 2019 to November 2020, skin scale specimens were collected from 5 body sites (cheeks, cubital fossa, back of the hand, abdomen, lower limbs) of 4 adult patients with severe AD in the acute and remission phases, who visited the outpatient clinic of Guangzhou Institute of Dermatology. The next-generation high-throughput sequencing was performed for metagenomic sequencing to construct the microbial gene catalogue of these specimens, followed by gene annotation and bioinformatics analysis for each sample.Results:A total of 18 phyla, 37 classes, 73 orders, 142 families, 237 genera, and 331 species were identified in the skin specimens from the 4 patients with severe AD. The patients with AD in the remission phase showed significantly increased diversity of skin microbiota and markedly different relative abundance of skin microorganisms compared with those in the acute phase (both P < 0.05). At the microbial species level, Staphylococcus aureus showed the highest impact on the acute phase of AD, while Staphylococcus epidermidis, Moraxella osloensis, Francisella sp., Staphylococcus cohnii, Staphylococcus warneri, Malassezia globosa and Malassezia restricta were enriched in the remission phase of AD with the absolute value of the common logarithm of the linear discriminant analysis score > 2 (Kruksal-Wallis test, all P < 0.05). As KEGG pathway enrichment analysis showed, the differentially abundant genes were annotated into a total of 355 functional pathways, of which 38 pathways were significantly enriched (all P < 0.05), mainly involving Staphylococcus aureus infection, tryptophan metabolism, histidine metabolism, nitrogen metabolism, metabolism of arginine and proline, biosynthesis and degradation of valine, leucine and isoleucine, fatty acid degradation, peroxisome proliferator-activated receptor signaling pathway, etc. Conclusion:The skin microecological structure significantly differed between the acute and remission phases among the patients with severe AD, which may be related to multiple functional pathways, such as Staphylococcus aureus infection, tryptophan metabolism, histidine metabolism and nitrogen metabolism.

MicroRNAs (miRNAs) are a class of non-coding RNA molecules that regulate gene expression after transcription and participate in various pathophysiological processes in the skin. In recent years, it has been reported that changes in miRNA expression profiles are related to some inflammatory skin diseases. For example, miR-203, miR-146a and miR-21 are upregulated in psoriatic lesions, miR-155 and miR-146a are upregulated in atopic dermatitis lesions, miR-21, miR-223, miR-142-3p and miR142-5p are upregulated in allergic contact dermatitis lesions; however, miR-146a and miR-155 are downregulated in peripheral blood of patients with systemic lupus erythematosus, and miR-223 is downregulated in dermatomyositis lesions. This review summarizes relationships of miRNAs with the occurrence and development of some inflammatory skin diseases.

Objective:To investigate the current situation of occupational hazards in automobile manufacturing enterprises in Shandong Province.Methods:From February to May 2019, the convenience sampling method was adopted to conduct on-site occupational health surveys with 20 automobile manufacturing enterprises in Shandong Province as the survey subjects, to detect the occupational hazard factors in the workplaces and individual exposure levels, and to analyze the occupational health check results of operators.Results:There were 13 small-sized, 4 medium-sized and 3 large-sized enterprises among the 20 automobile manufacturing enterprises. The detection results of benzene and toluene in the workplaces met the occupational exposure limits, and the detection results of welding fumes, manganese and its compounds, and xylene exceed the occupational exposure limits. The maximum short-term exposure concentration ( CSTE) of welding fume in the air of workplaces was 24.23 mg/m 3, and the over-standard rate was 11.0% (16/146) . The maximum time-weighted average concentration ( CTWA) of welding fume of operators is 10.60 mg/m 3, and the over-standard rate was 11.0% (8/73) . The maximum CSTE of manganese and its compounds in the air of workplaces was 0.879 mg/m 3, and the of manganese and its compounds of operators was 0.175 mg/m 3, and the over-standard rate was 5.7% (4/70) . The maximum xylene CSTE in the air of workplaces was 230.00 mg/m 3, and the over-standard rate was 3.9% (2/51) . The maximum xylene CTWA of operators was 70.40 mg/m 3, the over-standard rate was 3.6% (1/28) . Among the 4775 workers exposed to occupational hazards, 38 (0.80%) were suspected of electric welder's pneumoconiosis, 27 (0.57%) were suspected of manganese poisoning and 31 (0.65%) were suspected of chronic low-concentration benzene and benzene series poisoning. The detection rates of suspected occupational diseases among workers in small and medium-sized enterprises were relatively high, 2.86% (30/1048) and 4.51% (51/1132) respectively. There was a statistically significant difference in the detection rates of suspected occupational diseases among the operators of different scale automobile manufacturers ( P<0.05) . Conclusion:The exposure levels of electric welding fumes, manganese and its compounds in welding jobs and xylene exposure levels in spray painting jobsin Shandong Province's automobile manufacturing enterprises are more serious. The supervision and management of occupational hygiene should be strengthened, the working environment should be improved, and the health of welding and painting workers should be protected.

Objective:To investigate the current situation of occupational hazards in automobile manufacturing enterprises in Shandong Province.Methods:From February to May 2019, the convenience sampling method was adopted to conduct on-site occupational health surveys with 20 automobile manufacturing enterprises in Shandong Province as the survey subjects, to detect the occupational hazard factors in the workplaces and individual exposure levels, and to analyze the occupational health check results of operators.Results:There were 13 small-sized, 4 medium-sized and 3 large-sized enterprises among the 20 automobile manufacturing enterprises. The detection results of benzene and toluene in the workplaces met the occupational exposure limits, and the detection results of welding fumes, manganese and its compounds, and xylene exceed the occupational exposure limits. The maximum short-term exposure concentration ( CSTE) of welding fume in the air of workplaces was 24.23 mg/m 3, and the over-standard rate was 11.0% (16/146) . The maximum time-weighted average concentration ( CTWA) of welding fume of operators is 10.60 mg/m 3, and the over-standard rate was 11.0% (8/73) . The maximum CSTE of manganese and its compounds in the air of workplaces was 0.879 mg/m 3, and the of manganese and its compounds of operators was 0.175 mg/m 3, and the over-standard rate was 5.7% (4/70) . The maximum xylene CSTE in the air of workplaces was 230.00 mg/m 3, and the over-standard rate was 3.9% (2/51) . The maximum xylene CTWA of operators was 70.40 mg/m 3, the over-standard rate was 3.6% (1/28) . Among the 4775 workers exposed to occupational hazards, 38 (0.80%) were suspected of electric welder's pneumoconiosis, 27 (0.57%) were suspected of manganese poisoning and 31 (0.65%) were suspected of chronic low-concentration benzene and benzene series poisoning. The detection rates of suspected occupational diseases among workers in small and medium-sized enterprises were relatively high, 2.86% (30/1048) and 4.51% (51/1132) respectively. There was a statistically significant difference in the detection rates of suspected occupational diseases among the operators of different scale automobile manufacturers ( P<0.05) . Conclusion:The exposure levels of electric welding fumes, manganese and its compounds in welding jobs and xylene exposure levels in spray painting jobsin Shandong Province's automobile manufacturing enterprises are more serious. The supervision and management of occupational hygiene should be strengthened, the working environment should be improved, and the health of welding and painting workers should be protected.

To unravel the genetic mechanisms of disease and physiological traits, it requires comprehensive sequencing analysis of large sample size in Chinese populations. Here, we report the primary results of the Chinese Academy of Sciences Precision Medicine Initiative (CASPMI) project launched by the Chinese Academy of Sciences, including the de novo assembly of a northern Han reference genome (NH1.0) and whole genome analyses of 597 healthy people coming from most areas in China. Given the two existing reference genomes for Han Chinese (YH and HX1) were both from the south, we constructed NH1.0, a new reference genome from a northern individual, by combining the sequencing strategies of PacBio, 10× Genomics, and Bionano mapping. Using this integrated approach, we obtained an N50 scaffold size of 46.63 Mb for the NH1.0 genome and performed a comparative genome analysis of NH1.0 with YH and HX1. In order to generate a genomic variation map of Chinese populations, we performed the whole-genome sequencing of 597 participants and identified 24.85 million (M) single nucleotide variants (SNVs), 3.85 M small indels, and 106,382 structural variations. In the association analysis with collected phenotypes, we found that the T allele of rs1549293 in KAT8 significantly correlated with the waist circumference in northern Han males. Moreover, significant genetic diversity in MTHFR, TCN2, FADS1, and FADS2, which associate with circulating folate, vitamin B12, or lipid metabolism, was observed between northerners and southerners. Especially, for the homocysteine-increasing allele of rs1801133 (MTHFR 677T), we hypothesize that there exists a "comfort" zone for a high frequency of 677T between latitudes of 35-45 degree North. Taken together, our results provide a high-quality northern Han reference genome and novel population-specific data sets of genetic variants for use in the personalized and precision medicine.

Objective: To identify differentially expressed genes in the transcriptome of the lesional versus nonlesional skin tissues of patients with moderate and severe atopic dermatitis (AD) , and to elucidate their roles in the pathogenesis of AD. Methods: From July to October in 2016, lesional and nonlesional skin tissues were obtained from 5 outpatients of Han nationality with AD in Guangzhou Institute of Dermatology, Institute of Dermatology, Guangzhou Medical University. The next-generation high-throughput transcriptome-wide RNA sequencing (RNA-seq) was performed to identify differentially expressed genes, which were subjected to GO function annotation and KEGG pathway analysis. Real-time fluorescence-based quantitative PCR (qRT-PCR) was conducted to verify differences in candidate gene expression between lesional and nonlesional skin tissues. Results: An average of 10.96 GBs sequence reads were acquired among 10 samples. A total of 21 729 genes were detected, including 19 268 known genes and 2 545 predicted novel genes. A total of 23 153 new transcripts were detected, of which 18 889 were new alternative splicing subtypes of known protein-coding genes, 2 545 were transcripts belonging to new protein-coding genes, and the remaining 1 719 belonged to long-stranded non-coding RNA. Totally, 78 differentially expressed genes were identified between the lesional and nonlesional skin tissues, including 69 upregulated and 11 downregulated genes in the lesional skin tissues. Among them, there were several genes known to be associated with AD inflammation (CXCL1/2/8, IL6/IL1β, MMP1, SERPINB4, S100A2, GZMB, OASL, OSM) and barrier (KRT16, FABP5, CYP1A1) and keratinocyte differentiation (IL-20) . GO analysis revealed that functions of 72 differentially expressed genes could be annotated. KEGG pathway analysis showed that the differentially expressed genes were grouped into 132 signaling pathways, of which 13 were significantly enriched, including the interleukin (IL) -17 pathway, NOD-like receptor signaling pathway, Toll-like receptor signaling pathway, etc. qRT-PCR showed that the mRNA expression levels of candidate genes CXCL1, KRT6A, IL36A, SERPINB4 and PSAPL1 was consistent with the transcriptome sequencing results. Conclusions Differentially expressed genes and related important regulatory signaling pathways were identified between the lesional and nonlesional skin tissues of patients with AD at the transcriptional level, and the IL-17 pathway was found to be mostly enriched in AD lesions in patients of Han nationality. These findings provide an important basis for further study on the pathogenesis of AD..

Objective To evaluate the effect of curcumin on phagocytic function of macrophages after the stimulation with exosomes from patients with systemic lupus erythematosus (SLE).Methods From February 2016 to November 2017,18 patients with active SLE and 18 healthy controls were enrolled from Guangzhou Institute of Dermatology and Sun Yat-sen Memorial Hospital,Sun Yat-sen University,and serum exosomes were extracted from these subjects.The exosomes from the healthy controls (CON-exo) and SLE patients (SLE-exo) as well as different concentrations (1,5,20 μmol/L) of curcumin were used alone or in combination to stimulate the acute monocytic leukemia cell line THP-1-derived macrophages.After coincubation of the stimulated macrophages with pHrodo TM Red indicator,flow cytometry was performed to determine the average fluorescence intensity,immunofluorescence staining to calculate the proportion of pHrodo TM Red-positive macrophages,and then the phagocytic activity of macrophages was assessed.Western blot analysis was conducted to determine the protein expression of CD 14 in the stimulated macrophages.Statistical analysis was carried out by Student-t test for comparison between two groups,oneway analysis of variance for comparison among several groups,and least significant difference (LSD)-t test for multiple comparisons.Results Flow cytometry showed that there were significant differences in the relative fluorescence intensity of macrophages among the CON-exo group,CON-exo + 20 μmol/L curcumin group,SLE-exo group and SLE-exo + 20 μmol/L curcumin group (101.3％ ± 14.05％,94.27％ ± 14.13％,41.02％ ± 9.54％ and 87.33％ ± 15.01％,respectively;F =10.81,P ＜ 0.01),and immunofluorescence staining revealed that the proportion of pHrodo Red-positive macrophages significantly differed among the above 4 groups (82.16％ ± 5.20％,81.33％ ± 4.51％,54.20％ ± 9.31％ and 71.23％ ± 5.43％ respectively;F =12.42,P ＜ 0.01).The fluorescence intensity of macrophages and proportion of pHrodo-positive macrophages were both significantly lower in the SLE-exo group than in the CON-exo group (t =5.26,5.35 respectively,both P ＜ 0.01) and SLE-exo + 20 μmol/L curcumin group (t =3.97,3.26 respectively,both P ＜ 0.05).Western blot analysis showed that there were significant differences in the protein expression ofCD14 among the CON-exo group,SLE-exo group,SLE-exo + 1 μmol/L curcumin group,SLE-exo + 5 μmol/L curcumin group and SLE-exo + 20 μmol/L curcumin group (96.33％ ± 13.65％,30.67％ ± 5.86％,45.24％ ± 8.89％,72.81％ ± 6.62％ and 90.67％ ± 12.66％ respectively;F =24.57,P ＜ 0.01).The protein expression of CD14 was significantly lower in the SLE-exo group than in the CON-exo group(t =8.06,P ＜ 0.001),SLEexo + 5 μmol/L curcumin group and SLE-exo + 20 μmol/L curcumin group(t =5.08,7.38,both P ＜ 0.001),and the CD14 level showed an increasing trend along with the increase in the concentration of curcumin.Conclusion Exosomes from SLE patients markedly inhibit the phagocytosis of macrophages,while curcumin can reverse this inhibitory effect.