ObjectiveTo investigate the noise level and influencing factors in metro platforms and station halls， thereby providing the scientific basis for the establishment of hygienic standards. MethodsDuring the morning peak（7：00‒9：30）and off-peak （9：30‒17：00） on weekdays， the noise levels were measured with noise meters at 39 monitoring points of 13 station platforms and 31 monitoring points of 6 station halls. The monitoring points arrangement and detection methods referred to the Examination methods for public places—Part 1： physical parameters（GB/T 18204.1‒2013）. ResultsThe measured noise level in the station ranged from 69.25 to 86.17 dB（A）， accounting for 44.74% below 75 dB（A）， 89.47% below 80 dB（A） and 97.37% below 85 dB（A）.The noise level of the platform ［（76.38±4.19） dB（A）］ was higher than that of the station hall ［（74.24±4.50） dB（A）］（P<0.01）. The noise level of the elevated platforms ［（80.01±2.25） dB（A）］ was higher than that of the underground platforms ［（75.73±4.13） dB（A）］（P<0.01）， and the noise level of the platforms without platform screen doors（PSD） ［（80.21±5.08） dB（A）］ was higher than that of platforms with PSD［（74.73±3.16） dB（A）］ （P<0.01）. No statistical significant differences were observed among the different areas of the platforms， monitoring periods， platform depth， exit mode and operation years （P>0.05）. ConclusionThe noise level in metro stations in the city does not fully meet the requirements of current relevant standards. It is suggested to take noise reduction measures to reduce the noise of metro stations.

OBJECTIVE To explore the clinical effect of concurrent chemoradiotherapy combined with nituzumab in the treatment of locally advanced nasopharyngeal carcinoma in Guangxi,Yunnan and Guizhou.METHODS A total of 80 patients with locally advanced nasopharyngeal carcinoma who were pathologically confirmed and admitted to Affiliated Hospital of Youjiang Ethnomedicine from July 2021 to July 2022 from ethnic minority areas near the border of Guangxi,Yunnan and Guizhou were selected as the subjects of this study.They were randomly divided into control group(standard concurrent chemoradiotherapy)and observation group(combined treatment with nituzumab on the basis of control group),with 40 cases in each group.The levels of tumor markers,oxidative stress indicators,adverse reactions,complications,and recent clinical efficacy of the two groups were compared.RESULTS After treatment,the levels of superoxide dismutase(SOD),cytokeratin 19 fragment antigen21-1(CYFRA21-1),squamous cell carcinoma associated antigen(SCCAg)and serum ferritin(SF)were significantly decreased in both groups,while nitric oxide(NO)and malondialdehyde(MDA)were significantly increased.The levels of SCCAg,SF,CYFRA21-1,NO and MDA in observation group were lower than those in control group,and the level of SOD was higher than those in control group(P<0.05).Compared with the control group,the objective response rate(ORR)in the observation group was increased(P<0.05).There was no significant difference in the incidence of adverse reactions between the two groups(P>0.05).There was no significant difference in the incidence of complications between the two groups(P>0.05).CONCLUSION Concurrent chemoradiotherapy combined with nituzumab can effectively improve the short-term survival rate and clinical efficacy of patients with locally advanced nasopharyngeal carcinoma,regulate tumor markers and oxidative stress levels,and alleviate the disease.

Celastrol and wilforlide A are the main active triterpenoids of the traditional Chinese medicine Lei Gong Teng, which have anti-tumour, anti-inflammatory and immunosuppressive activities, and are the material basis for the clinical efficacy of Lei Gong Teng-related Chinese medicinal preparations. By analysing the biosynthetic pathway of active ingredients, optimizing genetic elements and utilizing "cell factory" to produce triterpenoids heterologously will be an effective way to obtain from Tripterygium wilfordii in the future in a "low-cost and high-efficient" manner. CYP712Ks are the first cytochrome P450s involved in the skeleton modification of friedelane-type and oleanane-type triterpenoids in T. wilfordii, and they can catalyse the generation of polpunonic acid from friedelin and 3-epi-katonic acid from β-amyrin by carboxylation at C-29 position. In this study, four multifunctional TwCYP712K1/2/3/5 were used to clarify the catalytic function and substrate selection preference using in vivo functional characterization in Saccharomyces cerevisiae. The spatial structure of the protein-substrate binding was clarified through homology modeling and molecular docking, and then the differential amino acids in the active pocket of the protein were mutated to clarify the crucial amino acids determining the catalytic function and the selection of substrate structure. A total of 63 mutant elements were constructed, and the amino acid sites affecting the carboxylation function of TwCYP712Ks were analyzed. In particular, the key amino acids affecting the substrate selectivity of TwCYP712K2 towards oleanane-type and friedelane-type triterpenoids were revealed and the TwCYP712K2^F127I and TwCYP712K2^A227T mutants would result in a reversal of the product ratio. In conclusion, four proteins of TwCYP712Ks were semi-rationally designed by homologous protein alignment and mutual mutation to elucidate multiple amino acid sites determining the catalytic function of the proteins, and a series of activity-enhancing or altering mutants were obtained, which provide abundant catalytic elements for the biosynthesis of active triterpenoids from T. wilfordii, and the mechanism of carboxylation in the C-29 position was initially elucidated.

[Objective]To investigate the impact of varying concentrations of baicalein on the proliferation and biological responses of MC3T3-E1 cells,as well as the antibacterial efficacy of baicalein against prevalent oral bacteria,and to elucidate the underlying mechanisms.[Methods]MC3T3-E1 cells were exposed to different concentrations of baicalein(0,6,12,18,and 24 μmol/L)and cell viability was determined by using the CCK-8 assay.Alkaline phosphatase(ALP)activity of MC3T3-E1 cells following osteogenic induction was assessed.RT-PCR was used to examine the expression of RunX2,BMP2,and Osterix.After 24 hours of treatment,the antibacterial potential of baicalein against Escherichia coli,Staphylococcus Aureus and Streptococcus Sanguis was evaluated by using the K-B paper disk method.[Results]Baicalein exhibited a modest reduction in proliferation of MC3T3-E1 cells but without affecting their sustained proliferation.Baicalein at a concentration of 18 μmol/L enhanced ALP activity of MC3T3-E1 cells,upregulated BMP2 and Osterix expression,downregulated RunX2 expression,significantly inhibited the proliferation of Staphylococcus Aureus and Streptococcus Sanguis(P<0.05).[Conclusions]Baicalein at an optimal concentration(18 μmol/L)demonstrated a promotional effect on the osteogenic differentiation of MC3T3-E1 cells and effectively suppressed the proliferation of common oral bacteria,including Staphylococcus Aureus and Streptococcus Sanguis.

Background::Total human immunodeficiency virus (HIV) DNA and integrated HIV DNA are widely used markers of HIV persistence. Droplet digital polymerase chain reaction (ddPCR) can be used for absolute quantification without needing a standard curve. Here, we developed duplex ddPCR assays to detect and quantify total HIV DNA and integrated HIV DNA.Methods::The limit of detection, dynamic ranges, sensitivity, and reproducibility were evaluated by plasmid constructs containing both the HIV long terminal repeat (LTR) and human CD3 gene (for total HIV DNA) and ACH-2 cells (for integrated HIV DNA). Forty-two cases on stable suppressive antiretroviral therapy (ART) were assayed in total HIV DNA and integrated HIV DNA. Correlation coefficient analysis was performed on the data related to DNA copies and cluster of differentiation 4 positive (CD4 +) T-cell counts, CD8 + T-cell counts and CD4/CD8 T-cell ratio, respectively. The assay linear dynamic range and lower limit of detection (LLOD) were also assessed. Results::The assay could detect the presence of HIV-1 copies 100% at concentrations of 6.3 copies/reaction, and the estimated LLOD of the ddPCR assay was 4.4 HIV DNA copies/reaction (95% confidence intervals [CI]: 3.6-6.5 copies/reaction) with linearity over a 5-log 10-unit range in total HIV DNA assay. For the integrated HIV DNA assay, the LLOD was 8.0 copies/reaction (95% CI: 5.8-16.6 copies/reaction) with linearity over a 3-log 10-unit range. Total HIV DNA in CD4 + T cells was positively associated with integrated HIV DNA ( r = 0.76, P <0.0001). Meanwhile, both total HIV DNA and integrated HIV DNA in CD4 + T cells were inversely correlated with the ratio of CD4/CD8 but positively correlated with the CD8 + T-cell counts. Conclusions::This ddPCR assay can quantify total HIV DNA and integrated HIV DNA efficiently with robustness and sensitivity. It can be readily adapted for measuring HIV DNA with non-B clades, and it could be beneficial for testing in clinical trials.

Objective To compare the efficacy and safety of vedolizumab(VDZ)and infliximab(IFX)for moderate to severe ulcerative colitis(UC)patients through a multicenter retrospective cohort study.Methods All patients with moderate to severe UC who were naive to biologic agents and treated with IFX or VDZ for at least 14 weeks at 3 hospitals in Southwest China between January 2021 and January 2023 were retrospectively enrolled.The efficacy evaluation indicators,including steroid-free clinical remission rates,clinical remission rates and endoscopic remission rates at weeks 14 and 52 were compared between the 2 groups.The occurrence of adverse events during treatment were recorded.Taking whether mucosal healing could be achieved after 14 and 52 weeks of treatment as the dependent variable,firstly,univariate analysis was performed to analyze the risk factors affecting mucosal healing at weeks 14 and 52,and then multivariate logistic regression analysis was applied to identify the independent risk factors of mucosal healing at the 2 time points.Results A total of 151 patients with moderate to severe UC were included,after propensity score matching(PSM),each group included 57 patients.There were no significant differences in the steroid-free clinical remission rate and clinical remission rate between the 2 groups at weeks 14 and 52(P＞0.05).The endoscopic remission rate at week 14 was significantly higher in the VDZ group than the IFX group[40.4％(23/57)vs 22.8％(13/57),P=0.044],but no such difference was observed at week 52[64.5％(20/31)vs 59.5％(22/37),P=0.669].Multivariate logistic regression analysis showed that left-sided disease(E2)[vs pancolitis(E3)](OR=0.46,95％CI:0.21～0.98,P=0.045)was independent risk factor for mucosal healing at week 14 and a disease duration ≥36 months(OR=0.25,95％CI:0.09～0.66,P=0.005)was independent risk factor for mucosal healing at week 52.No statistical difference was observed in the incidence of adverse events between the 2 groups(1.8％vs 7.0％,P=0.360).Conclusion VDZ and IFX have similar efficacy and safety,and both can be used as first-line options for patients with moderate to severe UC.

Objective To investigate the improvement effect and mechanism of marmesin on cognitive impairment in Alzheimer's disease(AD)mice.Methods Fifty mice were randomly divided into five groups:blank group,model group,low-and high-dose marmesin groups and donepezil(positive drug)group,with 10 mice in each group.After 21 days of continuous administration,except for the blank group,the mice in other groups were given intraperitoneal injection of scopolamine to establish the AD model.Network pharmacology was used to construct the protein-protein interaction(PPI)network of common targets of marmesin in the treatment of AD,and gene ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis were performed to provide further research direction.The cognitive function of AD model mice was evaluated by Morris water maze,open field test and new object recognition test.Nissl staining was used to observe the damage of hippocampal neurons.The levels of acetylcholine(Ach),acetylcholine transferase(ChAT),acetylcholinesterase(AChE),reactive oxygen species(ROS),malondialdehyde(MDA)and catalase(CAT)in hippocampus of mice were detected by kit.The protein expression levels of interleukin 6(IL-6),interleukin 1β(IL-1 β),tumor necrosis factor α(TNF-α),nuclear factor E2-related factor 2(NRF2),silent information regulator homologous protein 3(SIRT3),Kelch-like ECH-associated protein 1(KEAP1),quinone oxidoreductase 1(NQO1)and heme oxygenase 1(HO-1)in hippocampus were detected by Western Blot.Results Compared with the model group,the latency of Morris water maze test was significantly shortened in the high-dose marmesin group,the time of entering the target area in the open field new object test and the movement distance in the central area of the open field were prolonged,the number of neurons in the hippocampal CA1 and CA3 regions was significantly increased,the levels of ChAT and Ach in the hippocampus were significantly increased,AChE level was significantly decreased,CAT level was significantly increased,ROS and MDA levels were significantly decreased,TNF-α expression level was decreased,SIRT3 and HO-1 expression levels were increased,and KE AP1 protein expression level was decreased,the differences being statistically significant(P＜0.05 or P＜0.01 or P＜0.001).Conclusion Marmesin can effectively improve the learning and memory impairment of AD mice,and its mechanism may be related to the activation of NRF2/SIRT3 signaling pathway,thereby alleviating oxidative stress level and neuroinflammation,and repairing cholinergic neuron function.

Objective:To compare the therapeutic effects of 0.05% cyclosporine and 0.1% fluorometholone eye drops in patients with moderate and severe dry eye.Methods:A randomized controlled study was conducted.Fifty-two patients (52 eyes) with moderate to severe dry eye in Tianjin Medical University Eye Hospital from August 2021 to December 2022 were enrolled and randomly divided into 0.05% cyclosporine group and 0.1% fluorometholone group by random number table method, with 26 cases (26 eyes) in each group.Patients received 0.05% cyclosporine eye drops (2 times/day) and 0.1% fluorometholone eye drops (2 times/day) combined with calf blood deproteinized extract eye drops (4 times/day) according to the grouping.Before and 1, 3 and 6 months after treatment, clinical symptoms and signs were observed and Ocular Surface Disease Index (OSDI) score, corneal fluorescein staining (CFS) score, Schirmer Ⅰ test (SⅠT), non-invasive first tear film break-up time (NIBUTf), and conjunctival goblet cell (CGC) density were recorded.Before treatment and after 6 months of treatment, changes in corneal nerves and dendritic cells (DC) were observed by in vivo confocal microscopy (IVCM).This study adhered to the Declaration of Helsinki and was approved by the Medical Ethics Committee of Eye Hospital of Tianjin Medical University (No.2021KY-17).Written informed consent was obtained from each subject. Results:Compared with the 0.1% fluorometholone group, CFS score decreased after 1 month of treatment, but SⅠT, NIBUTf and CFS score increased after 3 months of treatment, and OSDI score, SⅠT and CFS score decreased after 6 months of treatment in the 0.05% cyclosporine group, showing statistically significant differences (all at P<0.05).Compared with baseline, in the 0.05% cyclosporine group, NIBUTf increased and CFS score decreased after 1 month of treatment, OSDI score and CFS score decreased, SⅠT and NIBUTf increased after 3 and 6 months of treatment, showing statistically significant differences (all at P<0.05).In the 0.1% fluorometholone group, CFS score decreased after 3 months of treatment, OSDI score and CFS score decreased, SⅠT increased after 6 months of treatment compared to baseline, showing statistically significant differences (all at P<0.05).OSDI score and CFS score decreased, SⅠT increased after 6 months of treatment compared to 3 months of treatment in the 0.05% cyclosporine group, and the differences were statistically significant (all at P<0.05).Baseline and CGC densities after 1, 3 and 6 months of treatment were (147.66±17.29), (195.44±15.46), (210.36±19.15) and (282.09±22.63)cells/mm 2 in the 0.05% cyclosporine group and (138.09±17.29), (95.67±15.46), (117.77±19.15) and (109.13±22.63)cells/mm 2 in the 0.1% fluorometholone group, respectively, with a statistically significant overall difference ( Fgroup=11.724, P<0.001; Ftime=4.837, P=0.005).Compared with the 0.1% fluorometholone group, CGC density in the 0.05% cyclosporine group increased after 1, 3 and 6 months of treatment, with statistically significant differences (all at P<0.05).Compared with baseline, the CGC density increased in the 0.05% cyclosporine group after 1, 3 and 6 months of treatment, and the differences were statistically significant (all at P<0.05).Compared with the 0.1% fluorometholone group, the corneal nerve fiber density in the 0.05% cyclosporine group increased after 6 months of treatment, and corneal DC density, area and dendrite number decreased, showing statistically significant differences (all at P<0.05). Conclusions:Cyclosporine 0.05% eye drops combined with calf blood deproteinized extract eye drops can improve symptoms and signs in patients with moderate to severe dry eye, and the long-term effect is better than that of 0.1% fluorometholone plus calf blood deproteinized extract eye drops.

Objective To monitor the susceptibility of clinical isolates to antimicrobial agents in tertiary hospitals in major regions of China in 2022.Methods Clinical isolates from 58 hospitals in China were tested for antimicrobial susceptibility using a unified protocol based on disc diffusion method or automated testing systems.Results were interpreted using the 2022 Clinical &Laboratory Standards Institute(CLSI)breakpoints.Results A total of 318 013 clinical isolates were collected from January 1,2022 to December 31,2022,of which 29.5％were gram-positive and 70.5％were gram-negative.The prevalence of methicillin-resistant strains in Staphylococcus aureus,Staphylococcus epidermidis and other coagulase-negative Staphylococcus species(excluding Staphylococcus pseudintermedius and Staphylococcus schleiferi)was 28.3％,76.7％and 77.9％,respectively.Overall,94.0％of MRSA strains were susceptible to trimethoprim-sulfamethoxazole and 90.8％of MRSE strains were susceptible to rifampicin.No vancomycin-resistant strains were found.Enterococcus faecalis showed significantly lower resistance rates to most antimicrobial agents tested than Enterococcus faecium.A few vancomycin-resistant strains were identified in both E.faecalis and E.faecium.The prevalence of penicillin-susceptible Streptococcus pneumoniae was 94.2％in the isolates from children and 95.7％in the isolates from adults.The resistance rate to carbapenems was lower than 13.1％in most Enterobacterales species except for Klebsiella,21.7％-23.1％of which were resistant to carbapenems.Most Enterobacterales isolates were highly susceptible to tigecycline,colistin and polymyxin B,with resistance rates ranging from 0.1％to 13.3％.The prevalence of meropenem-resistant strains decreased from 23.5％in 2019 to 18.0％in 2022 in Pseudomonas aeruginosa,and decreased from 79.0％in 2019 to 72.5％in 2022 in Acinetobacter baumannii.Conclusions The resistance of clinical isolates to the commonly used antimicrobial agents is still increasing in tertiary hospitals.However,the prevalence of important carbapenem-resistant organisms such as carbapenem-resistant K.pneumoniae,P.aeruginosa,and A.baumannii showed a downward trend in recent years.This finding suggests that the strategy of combining antimicrobial resistance surveillance with multidisciplinary concerted action works well in curbing the spread of resistant bacteria.

Primary intestinal diffuse large B-cell lymphoma(PI-DLBCL)is clinically rare,but in recent years,with the gradual maturity of pathology and molecular biology technology,its incidence rate and diagnosis rate have also increased.Due to the lack of specificity of the clinical symptoms of PI-DLBCL,it is easy to misdiagnose and miss the diagnosis,and there is no consensus on the best treatment of PI-DLBCL in clinical practice.Therefore,by retrieving the latest literature at home and abroad,this review systematically discusses the pathogenesis,clinical manifestations,diagnostic criteria,treatment and prognosis of PI-DLBCL,in order to improve the understanding of rare PI-DLBCL in hematology and oncology,and provide reference for basic research and clinical diagnosis and treatment of PI-DLBCL.