ObjectiveTo investigate the influence of histone deacetylase 3 (HDAC3) on the occurrence, development of psoriasis-like inflammation in mice, and the relative immune mechanisms. MethodsHealthy C57BL/6 mice aged 6-8 weeks were selected and randomly divided into 3 groups: control group (Control), psoriasis model group (IMQ), and HDAC3 inhibitor RGFP966-treated psoriasis model group (IMQ+RGFP966). One day prior to the experiment, the back hair of the mice was shaved. After a one-day stabilization period, the mice in Control group was treated with an equal amount of vaseline, while the mice in IMQ group was treated with imiquimod (62.5 mg/d) applied topically on the back to establish a psoriasis-like inflammation model. The mice in IMQ+RGFP966 group received intervention with a high dose of the HDAC3-selective inhibitor RGFP966 (30 mg/kg) based on the psoriasis-like model. All groups were treated continuously for 5 d, during which psoriasis-like inflammation symptoms (scaling, erythema, skin thickness), body weight, and mental status were observed and recorded, with photographs taken for documentation. After euthanasia, hematoxylin-eosin (HE) staining was used to assess the effect of RGFP966 on the skin tissue structure of the mice, and skin thickness was measured. The mRNA and protein expression levels of HDAC3 in skin tissues were detected using reverse transcription real-time quantitative polymerase chain reaction (RT-qPCR) and Western blot (WB), respectively. Flow cytometry was employed to analyze neutrophils in peripheral blood and lymph nodes, CD4⁺ T lymphocytes, CD8⁺ T lymphocytes in peripheral blood, and IL-17A secretion by peripheral blood CD4⁺ T lymphocytes. Additionally, spleen CD4⁺ T lymphocyte expression of HDAC3, CCR6, CCR8, and IL-17A secretion levels were analyzed. Immunohistochemistry was used to detect the localization and expression levels of HDAC3, IL-17A, and IL-10 in skin tissues. ResultsCompared with the Control group, the IMQ group exhibited significant psoriasis-like inflammation, characterized by erythema, scaling, and skin wrinkling. Compared with the IMQ group, RGFP966 exacerbated psoriasis-like inflammatory symptoms, leading to increased hyperkeratosis. The psoriasis area and severity index (PASI) skin symptom scores were higher in the IMQ group than those in the Control group, and the scores were further elevated in the IMQ+RGFP966 group compared to the IMQ group. Skin thickness measurements showed a trend of IMQ+RGFP966>IMQ>Control. The numbers of neutrophils in the blood and lymph nodes increased sequentially in the Control, IMQ, and IMQ+RGFP966 groups, with a similar trend observed for CD4⁺ and CD8⁺ T lymphocytes in the blood. In skin tissues, compared with the Control group, the mRNA and protein levels of HDAC3 decreased in the IMQ group, but RGFP966 did not further reduce these expressions. HDAC3 was primarily located in the nucleus. Compared with the Control group, the nuclear HDAC3 content decreased in the skin tissues of the IMQ group, and RGFP966 further reduced nuclear HDAC3. Compared with the Control and IMQ groups, RGFP966 treatment decreased HDAC3 expression in splenic CD4⁺ and CD8⁺ T cells. RGFP966 treatment increased the expression of CCR6 and CCR8 in splenic CD4⁺ T cells and enhanced IL-17A secretion by peripheral blood and splenic CD4⁺ T lymphocytes. Additionally, compared with the IMQ group, RGFP966 reduced IL-10 protein levels and upregulated IL-17A expression in skin tissues. ConclusionRGFP966 exacerbates psoriatic-like inflammatory responses by inhibiting HDAC3, increasing the secretion of the cytokine IL-17A, and upregulating the expression of chemokines CCR8 and CCR6.

Background Protein tyrosine phosphatase non-receptor type II (PTPN2) is essential for the regulation of inflammation and immunity, but the specific mechanism of action of Ptpn2 in silicosis is unknown. Objective To investigate the regulatory role of overexpression of Ptpn2 in SiO₂-mediated inflammatory response in alveolar type II epithelial cells based on transcriptome sequencing. Methods This study was an in vitro study. A negative control group (vector transferred) and an overexpression of Ptpn2 group of mouse lung epithelial cell line MLE-12 cells were firstly constructed. Transcriptome sequencing was performed to detect differentially expressed genes (DEGs), differentially expressed mRNAs, and differentially expressed ncRNAs in the two groups of MLE-12 cells, and then the DEGs were analyzed by the Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG). Constructed MLE-12 cells and A549 cells were stimulated using SiO₂ suspension, and divided into a negative control group (vector transferred), an overexpression of Ptpn2 group, a negative control + SiO₂ group, and an overexpression of Ptpn2 + SiO₂ group, respectively. Protein expressions of tumor necrosis factor-α (TNF-α) and interleukin (IL)-17A, IL-2, IL-1β were detected by Western blot. Positive TNF-α expression was detected by immunofluorescence staining. Results The results of Western blot showed that the protein expression level of PTPN2 was up-regulated in the overexpressed Ptpn2 group compared with the negative control group (P < 0.05). The volcano plot and clustering heat map showed that there were 1122 DEGs, 3681 differentially expressed mRNAs, and 474 differentially expressed ncRNAs in the overexpressed Ptpn2 group compared with the negative control group. The results of GO enrichment showed that, in terms of the biological process, the DEGs were mainly related to the regulation of metal ion transport, extracellular matrix organization, and extracellular structural organization; in terms of cellular composition, the DEGs were mainly related to collagen-containing extracellular matrix, receptor complexes, and basement membranes; in terms of molecular function, the DEGs were mainly related to the extracellular matrix structural constituents, glycosaminoglycan binding, and semaphorin receptor binding. The results of KEGG enrichment showed that the DEGs were closely related to cytokin-cytokine receptor interaction, IL-17 signaling pathway, TNF signaling pathway, and chemokine signaling pathway. In MLE-12 and A549 cells, the results of Western blot showed that the protein expression levels of TNF-α , IL-17A, IL-2, and IL-1β were up-regulated in the negative control + SiO₂ group compared with the negative control group (P < 0.05), and the protein expression levels of TNF-α, IL-17A, IL-2, and IL-1β were down-regulated in the overexpression of Ptpn2 + SiO₂ group compared with the negative control + SiO₂ group (P < 0.05). The immunofluorescence staining showed that the expression of TNF-α was increased in the negative control + SiO₂ group compared with the negative control group, and decreased in the overexpression of Ptpn2 + SiO₂ group compared with the negative control + SiO₂ group. Conclusion Overexpression of Ptpn2 inhibits SiO₂-mediated inflammatory response in MLE-12 cells and A549 cells.

Objective To systematically evaluate the efficacy and safety of proximal gastrectomy (PG) versus total gastrectomy (TG) for the treatment of Siewert type Ⅱ/Ⅲ adenocarcinoma of the esophagogastric junction (AEG). Methods PubMed, The Cochrane Library, Web of Science, EMbase, CNKI, Wanfang, and VIP databases were searched for literature comparing the efficacy and safety of PG and TG for the treatment of Siewert type Ⅱ/Ⅲ AEG. The search period was from database inception to March 2023. Meta-analysis was performed using Review Manager 5.4 software. Results A total of 23 articles were included, including 16 retrospective cohort studies, 5 prospective cohort studies, and 2 randomized controlled trials. The total sample size was 2 826 patients, with 1 389 patients undergoing PG and 1 437 patients undergoing TG. Meta-analysis results showed that compared with TG, PG had less intraoperative blood loss [MD=−19.85, 95%CI (−37.20, −2.51), P=0.02] and shorter postoperative hospital stay [MD=−1.23, 95%CI (−2.38, −0.08), P=0.04]. TG had a greater number of lymph nodes dissected [MD=−6.20, 95%CI (−7.68, −4.71), P<0.001] and a lower incidence of reflux esophagitis [MD=3.02, 95%CI (1.24, 7.34), P=0.01]. There were no statistically significant differences between the two surgical approaches in terms of operative time, postoperative survival rate (1-year, 3-year, 5-year), and postoperative overall complications (P>0.05). Conclusion PG has advantages in terms of intraoperative blood loss and postoperative hospital stay, while TG has advantages in terms of the number of lymph nodes dissected and the incidence of reflux esophagitis. There is no significant difference in long-term survival between the two surgical approaches.

Emerging mycotoxins are mycotoxins that have emerged in recent years, encompassing more than ten different families of mycotoxins, primarily Alternaria toxins (ATs), enniatins (ENNs), and beauvericin (BEA). These contaminants are widely found in a variety of food groups including cereals, fruits and vegetables, beer, wine, beans, and potatoes. Studies have shown that multiple physiological toxicities of the emerging mycotoxins are identified in plants, animals, and various human cell lines, and their presence are associated with certain human diseases. Notably, the emerging mycotoxins are not only prevalent in food but also frequently detected in human biological samples (e.g., serum, urine, and breast milk). Furthermore, multiple risk assessment studies have indicated that dietary exposure to the emerging mycotoxins, particularly ATs, exceed safe levels in some populations, posing potential threats to both food safety and human health. This article reviewed the contamination and physiological toxicity of three major emerging mycotoxins—ATs, ENNs, and BEA—in food, as well as research progress in human exposure assessment by different risk evaluation methods (e.g., dietary contamination & intake assessment and human biomonitoring). Additionally, it discussed current research challenges and unresolved scientific issues, aiming to provide insights for the biological control of emerging mycotoxins in food and the assessment of their exposure risks in human populations.

Background Deoxynivalenol (DON), a priority contaminant for food safety risk monitoring, is produced by Fusarium spp. infesting crops, and its common derivatives are 3-acetyl-DON (3A-DON) and 15-acetyl-DON (15A-DON), which have been shown to possess gastrointestinal toxicity, immunotoxicity, reproductive toxicity, and cytotoxicity. Due to the stable physicochemical properties of the DON family of toxins (DONs), they cannot be effectively removed during food processing, thus following the food chain, entering the human body, and posing health risks. Objective To understand the contamination status of DONs in commercial foods (cereals and bakery products) in Shanghai in 2022–2023, and to assess the exposure risk of DONs in pregnant women by combining their dietary consumption data. Methods Liquid chromatography tandem mass spectrometry (LC-MS/MS) was used to determine the contamination level of DONs in 1 100 food samples (cereals and baked goods) collected in 2022 and 944 samples collected in 2023 from Shanghai. The dietary monitoring data of pregnant women in Shanghai from 2016 to 2017 were adopted. The monitoring employed the food frequency questionnaire distributed among pregnant women through a combination of online telephone enquiry and offline on-site face-to-face survey to estimate their food consumption levels. An exposure assessment model was established to calculate the exposure level to DONs, and the probability distribution of the DONs exposure level in the pregnant women group in Shanghai was obtained by applying @Risk 7.5 software and simulating the calculation according to the Monte Carlo principle. With reference to the tolerable daily intake (TDI) of DONs [1.00 µg·(kg·d)⁻¹] proposed by the Joint FAO/WHO Expert Committee on Food Additives, the risk of exposure to DONs from commercial cereals and bakery products in pregnant women in Shanghai was assessed. Results DONs were detected in cereal and bakery samples collected in 2022 and 2023 with different levels of contamination. The level of DONs in cereal foods in 2023 (mean: 36.33 µg·kg⁻¹) decreased compared to 2022 (mean: 23.64 µg·kg⁻¹). However, the positive rate (71.67%) and level (mean: 51.22 µg·kg⁻¹) of DONs in bakery products increased significantly compared with 2022 (positive rate: 10.00%, mean: 24.39 µg·kg⁻¹). The mean consumption of cereals in 783 pregnant women was 222.48 g·d⁻¹ and the mean consumption of bakery products was 36.07 g·d⁻¹, and there was no statistically significant difference in the intake of all types of cereals and bakery products across the early, middle, and late stages of pregnancy. The modelled intakes of DONs via commercial cereals and bakery products for pregnant women in Shanghai were calculated to be 0.20 and 0.57 µg·(kg·d)⁻¹ in 2022 for the mean level and the 95th percentile level, respectively, and 0.16 µg·(kg·d)⁻¹ and 0.35 µg·(kg·d)⁻¹ in 2023, respectively. The results of the health risk assessment showed that pregnant women in Shanghai had 2.6% and 1.4% probability of exposure to DONs from cereal consumption in 2022 and 2023, respectively. Conclusion The risk of exposure of pregnant women in Shanghai to DONs via commercial cereals and bakery products is relatively low (1.4%-2.6%). However, considering the physical sensitivity of pregnant women, they should avoid consuming moldy grains and appropriately reduce intake of bakery products.

Objective To obtain the metabolomics characteristics of patients in the active stage of ulcerative colitis(UC)with syndrome of dampness-heat in large intestine through non-target metabolomics technology,and to provide a basis for promoting the theoretical system of traditional Chinese medicine(TCM)syndrome differentiation of disease syndrome combination and micro-macro combinations.Methods Non-target metabolomics technology was used to detect the serum samples from 159 patients in the active stage of UC(81 cases with syndrome of dampness-heat in large intestine and 78 cases with syndrome of non-dampness-heat in large intestine)and 30 healthy volunteers.The orthogonal partial sample least squares discriminant analysis model was constructed to screen metabolites with significant changes among groups.The variable importance in projection≥1,P<0.05,and fold change(FC)>1.20 or FC<0.83 were used as the criteria for the screening of differential metabolites.The Kyoto Encyclopedia of Genes and Genomes(KEGG)was used to annotate differential metabolites,and MetaboAnalyst software was used for pathway analysis.Results Between patients in active stage of UC with syndrome of dampness-heat in large intestine and syndrome of non-dampness-heat in large intestine,a total of 99 differential metabolites were screened in the positive ion mode,of which 48 were upregulated and 51 were downregulated.In the negative ion mode,a total of 38 differential metabolites were screened,of which 19 were upregulated and 19 were downregulated.The KEGG enrichment analysis showed that there were 21 metabolic pathways,and the pathway analysis showed that there were mainly four metabolic pathways involved in tryptophan metabolism,sphingolipid metabolism,glycerophospholipid metabolism,and pyrimidine metabolism.Conclusion Patients in the active stage of UC with syndrome of dampness-heat in large intestine have abnormal metabolic pathways,which can provide a basis for TCM syndrome differentiation and treatment for UC with syndrome of dampness-heat in large intestine.

Objective To analyze the diagnostic quality of imported malaria in Hubei Province from 2019 to 2022, and to further improve the diagnostic level and consolidate the achievements in eliminating malaria. Methods The samples of reported malaria cases in Hubei were collected by the provincial reference laboratory (PRL) from 2019 to 2022. The microscopy and fluorescent PCR were performed to confirm the infection of plasmodium species of each case．The positive coincidence rate and species coincidence rate were analyzed and compared． Results A total of 257 imported malaria cases were reported in Hubei Province from 2019 to 2022. Among 229 malaria cases were confirmed, the overall coincidence for malaria diagnosis was 91.24% (229/251), and the overall coincidence rate for parasite species identification was 86.03% (197/229). The difference in species coincidence rate among different years was statistically significant (χ²=10.458, P<0.05). The coincidence rates of malaria diagnosis and parasite species identification in different cities (prefectures) of Hubei Province were 71.43% to 100.00% and 50.00% to 100.00%, respectively, with significant differences among different regions (χ²=29.283, P<0.05). The coincidence rates of malaria diagnosis and parasite species identification were 72.73% to 100.00% and 0.00% to 100.00% in different diagnostic institutions, and the coincidence rate of species identification in hospitals (87.61%) was higher than that in Centers for Disease Control institutions (54.55%) (χ²=81.275, P<0.05). The coincidence rates of Plasmodium falciparum, P. vivax, P. malariae, and P. ovale identification were 91.50%, 88.57%, 80.00%, and 58.06%, respectively (χ²=19.777, P<0.05). Conclusion The quality of the qualitative diagnosis of malaria cases reported online from 2019 to 2022 is generally high. However, the ability of Plasmodium typing needs to be improved. In the future, technical training and quality control should be strengthened to improve the malaria surveillance capability during the post-elimination stage.

Objective To summarize the prescription and medication rules for the treatment of diabetes mellitus by contemporary Lingnan famous Chinese medical practitioners through data mining analysis.Methods The literature on treating diabetes mellitus by contemporary Lingnan famous Chinese medical practitioners were retrieved from the databases of CNKI,Wanfang and VIP,and the collections of clinical experience and medical cases of contemporary Lingnan famous practitioners were also reviewed to screen the relevant medical records of diabetes mellitus treated by Lingnan famous practitioners.The information of Chinese medicine prescriptions for diabetes mellitus in the medical records was input to Excel to establish a database,and then the frequency analysis was performed in terms of the nature,flavors and meridian tropism,therapeutic-action classification of the Chinese herbal medicines and traditional Chinese medicine(TCM)syndrome types.Moreover,the association rule analysis and cluster analysis were carried out using IBM SPSS Modeler 18.0 and SPSS Statistics 26.0.Results A total of 62 medical records of diabetes mellitus treated by the 24 contemporary Lingnan famous Chinese medical practitioners such as DENG Tie-Tao,LIU Shi-Chang,XIONG Man-Qi,LI Sai-Mei,ZHU Zhang-Zhi,LIU Min,and FAN Guan-Ji were screened out for the analysis.And a total of 101 prescriptions involving 210 Chinese herbal medicines were included.There were 29 commonly-used Chinese medicines with a frequency being or more than 15 times,and they were Glycyrrhizae Radix et Rhizoma Praeparata cum Melle,Astragali Radix,Bupleuri Radix,Puerariae Lobatae Radix,Poria,Atractylodis Macrocephalae Rhizoma,Codonopsis Radix,Scutellariae Radix,etc.According to the therapeutic action,the Chinese medicines were mainly classified into the categories of drugs for supplementing the deficiency,drugs for clearing heat,and drugs for dispelling wind-damp.The primary syndrome types were syndrome of deficiency of both spleen and kidney and syndrome of liver stagnation and spleen deficiency,and the syndromes were usually complicated with the syndrome elements of qi deficiency,yin deficiency,yang deficiency,cold-damp,phlegm-damp,and damp-heat.The association rule analysis yielded 28 core drug combinations consisting of 2-4 herbs,and the cluster analysis yielded 5 new candidate prescriptions,which were mainly derived from the modification of classical formulas such as Xiao Chaihu Decoction,Fuzi Lizhong Decoction,Yuquan Pills plus Zengye Decoction,and Zuogui Pills.Conclusion For the treatment of diabetes mellitus,contemporary Lingnan famous Chinese medical practitioners primarily adopt the methods of invigorating spleen and warming kidney,and soothing liver,draining dampness and resolving turbidity,which has more distinctive regional characteristics of Lingnan and can provide a reference for syndrome differentiation and treatment of diabetes mellitus in the Lingnan area.

Objective To explore the efficacy and safety of recombinant human anti-severe acute respiratory syn-drome coronavirus 2(anti-SARS-CoV-2)monoclonal antibody injection(F61 injection)in the treatment of patients with coronavirus disease 2019(COVID-19)combined with renal damage.Methods Patients with COVID-19 and renal damage who visited the PLA General Hospital from January to February 2023 were selected.Subjects were randomly divided into two groups.Control group was treated with conventional anti-COVID-19 therapy,while trial group was treated with conventional anti-COVID-19 therapy combined with F61 injection.A 15-day follow-up was conducted after drug administration.Clinical symptoms,laboratory tests,electrocardiogram,and chest CT of pa-tients were performed to analyze the efficacy and safety of F61 injection.Results Twelve subjects(7 in trial group and 5 in control group)were included in study.Neither group had any clinical progression or death cases.The ave-rage time for negative conversion of nucleic acid of SARS-CoV-2 in control group and trial group were 3.2 days and 1.57 days(P=0.046),respectively.The scores of COVID-19 related target symptom in the trial group on the 3rd and 5th day after medication were both lower than those of the control group(both P＜0.05).According to the clinical staging and World Health Organization 10-point graded disease progression scale,both groups of subjects improved but didn't show statistical differences(P＞0.05).For safety,trial group didn't present any infusion-re-lated adverse event.Subjects in both groups demonstrated varying degrees of elevated blood glucose,elevated urine glucose,elevated urobilinogen,positive urine casts,and cardiac arrhythmia,but the differences were not statistica-lly significant(all P＞0.05).Conclusion F61 injection has initially demonstrated safety and clinical benefit in trea-ting patients with COVID-19 combined with renal damage.As the domestically produced drug,it has good clinical accessibility and may provide more options for clinical practice.

Objective To investigate the current situation and influencing factors of latent tuberculosis infection(LTBI)among close contacts of positive etiology pulmonary tuberculosis(PTB)patients,provide basis for formula-ting intervention measures for LTBI.Methods A multi-stage stratified cluster random sampling method was used to select close contacts of positive etiology PTB patients from 39 districts and counties in Chongqing City as the study objects.Demographic information was collected by questionnaire survey and the infection of Mycobacterium tuberculosis was detected by interferon gamma release assay(IGRA).The influencing factors of LTBI were analyzed by x2 test and binary logistic regression model.Results A total of 2 591 close contacts were included,the male to female ratio was 0.69∶1,with the mean age of(35.72±16.64)years.1 058 cases of LTBI were detected,Myco-bacterium tuberculosis latent infection rate was 40.83％.Univariate analysis showed that the infection rate was dif-ferent among peoples of different age,body mass index(BMI),occupation,education level,marital status,wheth-er they had chronic disease or major surgery history,whether they lived together with the indicator case,and whether the cumulative contact time with the indicator case ≥250 hours,difference were all statistically significant(all P＜0.05);infection rate presented increased trend with the increase of age and BMI(both P＜0.001),and decreased trend with the increase of education(P＜0.05).Logistic regression analysis showed that age 45-54 years old(OR=1.951,95％CI:1.031-3.693),age 55-64 years old(OR=2.473,95％CI:1.279-4.781),other occupations(OR=0.530,95％CI:0.292-0.964),teachers(OR=0.439,95％CI:0.242-0.794),students(OR=0.445,95％CI:0.233-0.851),junior high school education or below(OR=1.412,95％CI:1.025-1.944),BMI＜18.5 kg/m2(OR=0.762,95％CI:0.586-0.991),co-living with indicator cases(OR=1.621,95％CI1.316-1.997)and cumu-lative contact time with indicator cases ≥250 hours(OR=1.292,95％CI:1.083-1.540)were the influential fac-tors for LTBI(all P＜0.05).Conclusion The close contacts with positive etiology PTB have a high latent infection rate of Mycobacterium tuberculosis,and it is necessary to pay attention to close contacts of high age,farmers,and frequent contact with patients,and take timely targeted interventions to reduce the risk of occurrence of disease.