OBJECTIVE: To determine the role of Tripterygium wilfordii multiglycoside (TGW) in the treatment of psoriatic dermatitis from a cellular immunological perspective. METHODS: Mouse models of psoriatic dermatitis were established by imiquimod (IMQ). Twelve male BALB/c mice were assigned to IMQ or IMQ₊TGW groups according to a random number table. Histopathological changes in vivo were assessed by hematoxylin and eosin staining. Ratios of immune cells and cytokines in mice, as well as PAM212 cell proliferation in vitro were assessed by flow cytometry. Pro-inflammatory cytokine expression was determined using reverse transcription quantitative polymerase chain reaction. RESULTS: TGW significantly ameliorated the severity of IMQ-induced psoriasis-like mouse skin lesions and restrained the activation of CD45⁺ cells, neutrophils and T lymphocytes (all P<0.01). Moreover, TGW significantly attenuated keratinocytes (KCs) proliferation and downregulated the mRNA levels of inflammatory cytokines including interleukin (IL)-17A, IL-23, tumor necrosis factor α, and chemokine (C-X-C motif) ligand 1 (P<0.01 or P<0.05). Furthermore, it reduced the number of γ δ T17 cells in skin lesion of mice and draining lymph nodes (P<0.01). CONCLUSIONS TGW improved psoriasis-like inflammation by inhibiting KCs proliferation, as well as the associated immune cells and cytokine expression. It inhibited IL-17 secretion from γ δ T cells, which improved the immune-inflammatory microenvironment of psoriasis.
Male ; Animals ; Mice ; Tripterygium ; Psoriasis/drug therapy* ; Keratinocytes ; Skin Diseases/metabolism* ; Cytokines/metabolism* ; Imiquimod/metabolism* ; Dermatitis/pathology* ; Disease Models, Animal ; Mice, Inbred BALB C ; Skin/metabolism*

Depression is a common neurological disorder with high incidence, high recurrence and high disability, but its pathogenesis is unclear. In recent years, the protective and attacking effects of glial cells on neurons have become the frontier of neurological disease research. Neuronal injury caused by abnormal activation of microglia (MG) plays an important role in the pathogenesis of depression. In this paper, through literature retrieval by GeenMedical and CNKI, the relevant pathways and key targets of MG activation in depression are summarized so as to provide a theoretical basis for further clinical research.

Platycodonis Radix is the dry root of Platycodon grandiflorum of Campanulaceae, which has a variety of pharmacological effects and is a commonly used bulk Chinese medicine. In this study, the chloroplast genome sequences of six P. grandiflorum from different producing areas has been sequenced with Illumina HiSeq X Ten platform. The specific DNA barcodes were screened, and the germplasm resources and genetic diversity were analyzed according to the specific barcodes. The total length of the chloroplast genome of 6 P. grandiflorum samples was 172 260-172 275 bp, and all chloroplast genomes showed a typical circular tetrad structure and encoded 141 genes. The comparative genomics analysis and results of amplification efficiency demonstrated that trnG-UCC and ndhG_ndhF were the potential specific DNA barcodes for identification the germplasm resources of P. grandiflorum. A total of 305 P. grandiflorum samples were collected from 15 production areas in 9 provinces, for which the fragments of trnG-UCC and ndhG_ndhF were amplificated and the sequences were analyzed. The results showed that trnG-UCC and ndhG_ndhF have 5 and 11 mutation sites, respectively, and 5 and 7 haplotypes were identified, respectively. The combined analysis of the two sequences formed 13 haplotypes (named Hap1-Hap13), and Hap4 is the main genotype, followed by Hap1. The unique haplotypes possessed by the three producing areas can be used as DNA molecular tags in this area to distinguish from the germplasm resources of P. grandiflorum from other areas. The haplotype diversity, nucleotide diversity and genetic distance were 0.94, 4.79×10^-3 and 0.000 0-0.020 3, respectively, suggesting that the genetic diversity was abundant and intraspecific kinship was relatively close. This study laid a foundation for the identification of P. grandiflorum, the protection and utilization of germplasm resources, and molecular breeding.

Objective To investigate whether Liuwei Dihuang Pills enhances the antigen cross-presenting ability of dendritic cell(DC)by increasing gap junctional intercellular communication(GJIC),and to explore the mechanisms involved.Methods Western Blot and immunofluorescence were used to observe the effects of Liuwei Dihuang Pills-containing serum on the expression and membrane localisation of gap junction protein connexin43(Cx43)in mouse melanoma cells(B16);Calcein-AM/DiI fluorescence tracer assay was used to observe the effects of Liuwei Dihuang Pills-containing serum on the function of GJIC in B16 cells;flow cytometry was used to observe the role of GJIC in the enhancement of DC antigen presenting ability by Liuwei Dihuang Pills-containing serum;and propidium iodide(PI)/Hoechst staining assay was used to observe the immunocidal effect of CD8+ T-lymphocytes.Results Western Blot and immunofluorescence experiments showed that Liuwei Dihuang Pills-containing serum led to the up-regulation of Cx43 expression;fluorescence tracer experiments proved that the GJIC function of B16 cells was significantly enhanced by Liuwei Dihuang Pills-containing serum;flow cytometry analyses showed that the DC antigen-presenting ability was enhanced by Liuwei Dihuang Pills-containing serum;and the results of PI/Hoechst staining showed that the immuno-killing effect of CD8+T-cells was more significant after the intervention of Liuwei Dihuang Pills-containing serum in B16-OVA.Conclusion Liuwei Dihuang Pills improve the GJIC function by up-regulating the Cx43 expression of melanoma cells,and then enhance the cross-presenting ability of DCs thus activating stronger CD8+ T-cell immunocidal responses.

AIM:To observe how total flavonoids of Pterocarya hupehensis Skan(PHSTF)affects the migra-tion and invasion of human rheumatoid fibroblast-like synoviocyte line MH7A.METHODS:The MH7A cells were divided into control group(without any treatment),low-,medium-and high-dose(6.25,12.5 and 25 mg/L,respectively)PHSTF groups,phosphatidylinositol 3-kinase(PI3K)inhibitor 740Y-P(10 μmol/L)group,and 740Y-P(10 μmol/L)+high-dose(25 mg/L)PHSTF group.The viability of the MH7A cells was determined by CCK-8 assay,while the migration and inva-sion were assessed by scratch and Transwell assays.The protein levels of matrix metalloproteinase-2(MMP-2),MMP-9,PI3K,p-PI3K,AKT and p-AKT were detected by Western blot.RESULTS:Compared with control group,the cell via-bility in PHSTF treatment groups was reduced(P<0.05),the cell wound healing area was significantly decreased(P<0.01),migratory and invasive cells in the lower chamber were significantly reduced(P<0.01),and the protein expres-sion of MMP-2 and MMP-9 and the ratios of p-PI3K/PI3K and pAKT/AKT were decreased(P<0.01).Compared with high-dose PHSTF group,the addition of PI3K/AKT pathway agonist 740Y-P significantly increased the migration and invasion ability of MH7A cells(P<0.01)and elevated the protein expression of MMP-2 and MMP-9 and the ratios of p-PI3K/PI3K and pAKT/AKT(P<0.01)under the treatment with PHSTF.CONCLUSION:Total flavonoids of Pterocarya hupehensis Skan could inhibit the migration and invasion of MH7A cells by regulating the PI3K/AKT signaling pathway.

Objective:To report the results of national surveillance on the distribution and antimicrobial resistance profile of clinical Gram-negative bacteria isolates from bloodstream infections in China in 2022.Methods:The clinical isolates of Gram-negative bacteria from blood cultures in member hospitals of national bloodstream infection Bacterial Resistant Investigation Collaborative System（BRICS）were collected during January 2022 to December 2022. Antibiotic susceptibility tests were conducted by agar dilution or broth dilution methods recommended by Clinical and Laboratory Standards Institute（CLSI）. WHONET 5.6 and SPSS 25.0 software were used to analyze the data.Results:During the study period，9 035 strains of Gram-negative bacteria were collected from 51 hospitals，of which 7 895（87.4%）were Enterobacteriaceae and 1 140（12.6%）were non-fermenting bacteria. The top 5 bacterial species were Escherichia coli（ n=4 510，49.9%）， Klebsiella pneumoniae（ n=2 340，25.9%）， Pseudomonas aeruginosa（ n=534，5.9%）， Acinetobacter baumannii complex（ n=405，4.5%）and Enterobacter cloacae（ n=327，3.6%）. The ESBLs-producing rates in Escherichia coli， Klebsiella pneumoniae and Proteus spp. were 47.1%（2 095/4 452），21.0%（427/2 033）and 41.1%（58/141），respectively. The prevalence of carbapenem-resistant Escherichia coli（CREC）and carbapenem-resistant Klebsiella pneumoniae（CRKP）were 1.3%（58/4 510）and 13.1%（307/2 340）；62.1%（36/58）and 9.8%（30/307）of CREC and CRKP were resistant to ceftazidime/avibactam combination，respectively. The prevalence of carbapenem-resistant Acinetobacter baumannii（CRAB）complex was 59.5%（241/405），while less than 5% of Acinetobacter baumannii complex was resistant to tigecycline and polymyxin B. The prevalence of carbapenem-resistant Pseudomonas aeruginosa（CRPA）was 18.4%（98/534）. There were differences in the composition ratio of Gram-negative bacteria in bloodstream infections and the prevalence of main Gram-negative bacteria resistance among different regions，with statistically significant differences in the prevalence of CRKP and CRPA（ χ2=20.489 and 20.252， P<0.001）. The prevalence of CREC，CRKP，CRPA，CRAB，ESBLs-producing Escherichia coli and Klebsiella pneumoniae were higher in provinicial hospitals than those in municipal hospitals（ χ2=11.953，81.183，10.404，5.915，12.415 and 6.459， P<0.01 or <0.05），while the prevalence of CRPA was higher in economically developed regions（per capita GDP ≥ 92 059 Yuan）than that in economically less-developed regions（per capita GDP <92 059 Yuan）（ χ2=6.240， P=0.012）. Conclusions:The proportion of Gram-negative bacteria in bloodstream infections shows an increasing trend，and Escherichia coli is ranked in the top，while the trend of CRKP decreases continuously with time. Decreasing trends are noted in ESBLs-producing Escherichia coli and Klebsiella pneumoniae. Low prevalence of carbapenem resistance in Escherichia coli and high prevalence in CRAB complex have been observed. The composition ratio and antibacterial spectrum of bloodstream infections in different regions of China are slightly different，and the proportion of main drug resistant bacteria in provincial hospitals is higher than those in municipal hospitals.

Pancreatic cancer is a highly lethal malignancy which can often be easily misdiagnosed by traditional imaging examinations and pathological analyses at an early stage, and the existing treatment options are constrained by individual differences and tumor heterogeneity. As an emerging technology, artificial intelligence shows great potential for application in medical science. This paper primarily focuses on the current application status and challenges of artificial intelligence in early diagnosis, imaging analysis, pathology, and personalized treatment of pancreatic tumor, and looks ahead to their application prospec in the diagnosis and treatment for this disease.

AIM: To explore the clinicopathological and immunohistochemistry(IHC)characteristics of meibomian gland carcinoma(MGC).METHODS: Patients who were pathologically diagnosed as MGC from January 1, 2015 to December 31, 2020 in our hospital were enrolled, and their clinicopathological information was retrospectively analyzed. Cancer tissues from all the cases were IHC stained. En Vision two-step method, DAB staining, as well as hematoxylin re-staining were applied in the IHC assay.RESULTS: A total of 50 patients with 21 males and 29 females(1:1.38)were enrolled in the study, ranging from 26 to 80 years old, with a median age of 60 years. The upper eyelid, which was the predilection site, accounting for 66%(33/50). Histopathologically, moderately or poorly differentiated was in the majority(35/50, 70%). The expression rates of IHC parameters of MGC patients were as follows: GATA-3(49/50, 98%), EMA(49/50, 98%), CAM5.2(42/50, 84%), AR(41/50, 82%), MSH2(50/50, 100%), MSH6(50/50, 100%), MLH1(50/50, 100%), PMS2(50/50, 100%), Ki67(positive, 50%-90%). All the patients were followed up for 12 to 72 mo, with 5 cases of recurrence and 0 deaths.CONCLUSION: Pathological diagnosis of MGC should focus on observing cancer cells' cytoplasm to find relevant clues for cortical gland differentiation. Comprehensive analysis of multiple indicators is required when using IHC to assist diagnosis. For most MGC cancer cells, positive expressions of GATA-3, EMA, AR, CAM5.2 and a high Ki67 proliferation index could be always found. In addition, screening for Muir-Torre syndrome related IHC indicators could be also performed in diagnosing MGC simultaneously.

Objective:To explore the bioaccessibility of the main metal components in welding fume welding fume in simulated lung fluid, and to evaluate the exposure level of each metal component in combination with the EPA inhalation exposure risk assessment model.Methods:In November 2022, the microscopic morphology characteristics of welding fumes were analyzed by scanning electron microscopy, the bioaccessibility of each metal component in lung fluid simulated normal and lung inflammatory states was analyzed by in vitro simulation method, and the exposure level of each metal component was calculated in combination with the EPA inhalation exposure risk assessment model.Results:The main metal components in carbon dioxide gas shielded welding fumes were Fe, Mn, Zn, Ti, Al, Cu, Cr, Cd, Ni and As, and the bioaccessibility in simulated normal lung interstitial fluid was 0.82%-1.84%, 5.07%-9.41%, 4.52%-7.23%, 5.10%-8.67%, 20.48%-29.60%, 5.27%-9.83%, 4.80%-7.56%, 0.07%-1.08%, 6.48%-13.84% and 33.02%-42.81%. The bioaccessibility of the above metal components in the lung fluid under simulated lung inflammation was 14.79%-27.45%, 34.53%-46.11%, 35.31%-59.13%, 16.45%-22.51%, 60.78%-76.51%, 26.58%-34.12%, 15.32%-25.87%, 2.0%-5.7%, 34.77%-43.33% and 71.34%-88.36%, respectively. Compared with the simulated lurg interstitial fluid, the bioaccessibility of metal components in the lung fluid under the simulated inflammatory state was increased, and the difference was statistically significant ( P<0.05). The average daily exposure dose Mn in the two simulated lung fluids exceeded the inhalation reference limit (>50 times), and the average daily exposure dose Ti and Cr in the simulated lung inflammation exceeded the reference limit (>1.3 times) . Conclusion:Attention should be paid to the bioaccessibility characteristics of metal components in the exposure level and hazard assessment of welding fumes.

Objective:To explore the bioaccessibility of the main metal components in welding fume welding fume in simulated lung fluid, and to evaluate the exposure level of each metal component in combination with the EPA inhalation exposure risk assessment model.Methods:In November 2022, the microscopic morphology characteristics of welding fumes were analyzed by scanning electron microscopy, the bioaccessibility of each metal component in lung fluid simulated normal and lung inflammatory states was analyzed by in vitro simulation method, and the exposure level of each metal component was calculated in combination with the EPA inhalation exposure risk assessment model.Results:The main metal components in carbon dioxide gas shielded welding fumes were Fe, Mn, Zn, Ti, Al, Cu, Cr, Cd, Ni and As, and the bioaccessibility in simulated normal lung interstitial fluid was 0.82%-1.84%, 5.07%-9.41%, 4.52%-7.23%, 5.10%-8.67%, 20.48%-29.60%, 5.27%-9.83%, 4.80%-7.56%, 0.07%-1.08%, 6.48%-13.84% and 33.02%-42.81%. The bioaccessibility of the above metal components in the lung fluid under simulated lung inflammation was 14.79%-27.45%, 34.53%-46.11%, 35.31%-59.13%, 16.45%-22.51%, 60.78%-76.51%, 26.58%-34.12%, 15.32%-25.87%, 2.0%-5.7%, 34.77%-43.33% and 71.34%-88.36%, respectively. Compared with the simulated lurg interstitial fluid, the bioaccessibility of metal components in the lung fluid under the simulated inflammatory state was increased, and the difference was statistically significant ( P<0.05). The average daily exposure dose Mn in the two simulated lung fluids exceeded the inhalation reference limit (>50 times), and the average daily exposure dose Ti and Cr in the simulated lung inflammation exceeded the reference limit (>1.3 times) . Conclusion:Attention should be paid to the bioaccessibility characteristics of metal components in the exposure level and hazard assessment of welding fumes.