Objective This study aimed to evaluate whether the onset of the plateau phase of slow hepatitis B surface antigen decline in patients with chronic hepatitis B treated with intermittent interferon therapy is related to the frequency of dendritic cell subsets and expression of the costimulatory molecules CD40,CD80,CD83,and CD86. Method This was a cross-sectional study in which patients were divided into a natural history group(namely NH group),a long-term oral nucleoside analogs treatment group(namely NA group),and a plateau-arriving group(namely P group).The percentage of plasmacytoid dendritic cell and myeloid dendritic cell subsets in peripheral blood lymphocytes and monocytes and the mean fluorescence intensity of their surface costimulatory molecules were detected using a flow cytometer. Results In total,143 patients were enrolled(NH group,n = 49;NA group,n = 47;P group,n = 47).The results demonstrated that CD141/CD1c double negative myeloid dendritic cell(DNmDC)/lymphocytes and monocytes(%)in P group(0.041[0.024,0.069])was significantly lower than that in NH group(0.270[0.135,0.407])and NA group(0.273[0.150,0.443]),and CD86 mean fluorescence intensity of DNmDCs in P group(1832.0[1484.0,2793.0])was significantly lower than that in NH group(4316.0[2958.0,5169.0])and NA group(3299.0[2534.0,4371.0]),Adjusted P all<0.001. Conclusion Reduced DNmDCs and impaired maturation may be associated with the onset of the plateau phase during intermittent interferon therapy in patients with chronic hepatitis B.

Objective To explore characteristics of clinical parameters and cytokines in patients with drug-induced liver injury(DILI)caused by different drugs and their correlation with clinical indicators. Method The study was conducted on patients who were up to Review of Uncertainties in Confidence Assessment for Medical Tests(RUCAM)scoring criteria and clinically diagnosed with DILI.Based on Chinese herbal medicine,cardiovascular drugs,non-steroidal anti-inflammatory drugs(NSAIDs),anti-infective drugs,and other drugs,patients were divided into five groups.Cytokines were measured by Luminex technology.Baseline characteristics of clinical biochemical indicators and cytokines in DILI patients and their correlation were analyzed. Results 73 patients were enrolled.Age among five groups was statistically different(P=0.032).Alanine aminotransferase(ALT)(P=0.033)and aspartate aminotransferase(AST)(P=0.007)in NSAIDs group were higher than those in chinese herbal medicine group.Interleukin-6(IL-6)and tumor necrosis factor alpha(TNF-α)in patients with Chinese herbal medicine(IL-6:P<0.001;TNF-α:P<0.001)and cardiovascular medicine(IL-6:P=0.020;TNF-α:P=0.001)were lower than those in NSAIDs group.There was a positive correlation between ALT(r=0.697,P=0.025),AST(r=0.721,P=0.019),and IL-6 in NSAIDs group. Conclusion Older age may be more prone to DILI.Patients with NSAIDs have more severe liver damage in early stages of DILI,TNF-α and IL-6 may partake the inflammatory process of DILI.

Objective:To assess the effectiveness of a 6-month Ba Duan Jin exercise program in improving the balance of community-dwelling older adults.Methods:A two arms, parallel-group, cluster randomized controlled trial was conducted in 1 028 community residents aged 60-80 years in 40 communities in 5 provinces of China. Participants in the intervention group (20 communities, 523 people) received Ba Duan Jin exercise 5 days/week, 1 hour/day for 6 months, and three times of falls prevention health education, and the control group (20 communities, 505 people) received falls prevention health education same as the intervention group. The Berg balance scale (BBS) score was the leading outcome indicator, and the secondary outcome indicators included the length of time of standing on one foot (with eyes open and closed), standing in a tandem stance (with eyes open and closed), the closed circle test, and the timed up to test.Results:A total of 1 028 participants were included in the final analysis, including 731 women (71.11%) and 297 men (28.89%), and the age was (69.87±5.67) years. After the 3-month intervention, compared with the baseline data, the BBS score of the intervention group was significantly higher than the control group by 3.05 (95% CI: 2.23-3.88) points ( P<0.001). After the 6-month intervention, compared with the baseline data, the BBS score of the intervention group was significantly higher than the control group by 4.70 (95% CI: 4.03-5.37) points ( P<0.001). Ba Duan Jin showed significant improvement ( P<0.05) in all secondary outcomes after 6 months of exercise in the intervention group compared with the control group. Conclusions:This study showed that Ba Duan Jin exercise can improve balance in community-dwelling older adults aged 60-80. The longer the exercise time, the better the improvement.

Objective Tissue uptake and distribution of nano-/microplastics was studied at a single high dose by gavage in vivo.Methods Fluorescent microspheres (100 nm, 3 μm, and 10 μm) were given once at a dose of 200 mg/(kg·body weight). The fluorescence intensity (FI) in observed organs was measured using the IVIS Spectrum at 0.5, 1, 2, and 4 h after administration. Histopathology was performed to corroborate these findings.Results In the 100 nm group, the FI of the stomach and small intestine were highest at 0.5 h, and the FI of the large intestine, excrement, lung, kidney, liver, and skeletal muscles were highest at 4 h compared with the control group (P < 0.05). In the 3 μm group, the FI only increased in the lung at 2 h (P < 0.05). In the 10 μm group, the FI increased in the large intestine and excrement at 2 h, and in the kidney at 4 h (P < 0.05). The presence of nano-/microplastics in tissues was further verified by histopathology. The peak time of nanoplastic absorption in blood was confirmed.Conclusion Nanoplastics translocated rapidly to observed organs/tissues through blood circulation;however, only small amounts of MPs could penetrate the organs.

OBJECTIVE To investigate the inhibitory effect and mechanism of lead(Pb2+)on γ-amino-butyric acid(GABA)A receptor-mediated currents(IGABA)and GABAergic synaptic transmission in rat cortical neurons.METHODS ①The cortical neurons from 0 d Sprague Dawley(SD)rats were cultured for experiments.The cultured cells(7-14 d)were recorded using the patch-clamp technique to analyze the effects of Pb2+ at different concentrations(1,5,10,50 and 100 μmol·L-1)on IGABA induced by GABA 100 μmol·L-1.② The effects of Pb2+ 50 μmol·L-1 on IGABA induced by GABA at different concentrations(1,10,50,100,500 and 100 μmol·L-1)were detected.③Brain slices(350 μm)were prepared from SD rats(15-19 d).The spontaneous inhibitory post-synaptic currents(sIPSCs),miniature inhibitory post-synaptic currents(mIPSCs)and current injection-induced action potential(AP)were recorded to detect the effects of Pb2+ 10 μmol·L-1 on the amplitude and frequency of sIPSCs and mIPSCs,and the frequency of AP.RESULTS ①Pb2+ inhibited IGABA in a concentration-dependent manner,and IC50 was(68±20)μmol·L-1.②Pb2+ also suppressed the maximum current induced by GABA(P<0.01),with a significant increase of the GABA′s EC50 from(20±6)μmol·L-1 to(87±39)μmol·L-1,indicating that Pb2+ might inhibit IGABA in a non-competitive mechanism.③Pb2+ 10 μmol·L-1 inhibited the frequency(P<0.01)rather than the ampli-tude of sIPSCs reversibly,but had no effect on eigher the frequency or amplitude of mIPSCs.In addi-tion,Pb2+ decreased the frequency of evoked AP by current injection(P<0.01)and reduced the overall excitability of rat cortical neurons.CONCLUSION Pb2+ can significantly inhibit IGABA in primary cultured neurons.In the brain slice experiment,Pb2+ may affect sIPSCs frequency by inhibiting the AP of cortical neurons,suggesting that there are different intrinsic mechanisms through which Pb2+ inhibits both IGABA in primary cultured neurons and the frequency of sIPSCs in brain slice neurons,which points to the complexity of the mechanism of Pb2+ poisoning.

Objective:To explore the prognostic factors of primary plasma cell leukemia (pPCL) in the era of novel agents.Methods:The clinical data of 66 patients with pPCL treated at the Department of Haematology, Beijing Chao-Yang Hospital, Capital Medical University from 2011 to 2022 were retrospectively collected to analyze their prognostic factors.Results:Among the 66 patients with pPCL, the median age was 59 (range: 29-79) years. The median overall survival (OS) duration was 19.0 (95% CI 10.4-27.6) months, and the median progression-free survival (PFS) duration was 11.0 (95% CI 6.5-15.6) months. The median OS and PFS were significantly longer in patients with the best post-treatment response of very good partial remission (VGPR) or better than in patients with a response of partial remission (PR) or worse (median OS: 33.0 months vs 6.0 months, P<0.001; median PFS: 16.0 months vs 3.0 months, P<0.001). OS was significantly longer in patients who underwent autologous hematopoietic stem cell transplantation than in those who did not undergo transplantation (49.0 months vs 6.0 months, P=0.002), and there was a trend toward a longer PFS in patients who underwent transplantation than in those who did not undergo transplantation (19.0 months vs 8.0 months, P=0.299). The median OS and PFS were significantly longer in patients who received maintenance therapy than in those who did not receive maintenance therapy (median OS: 56.0 months vs 4.0 months, P<0.001; median PFS: 20.0 months vs 2.0 months, P<0.001). Multivariate analysis showed that hypercalcemia was an independent risk factor ( HR=3.204, 95% CI 1.068-9.610, P=0.038) for patients with pPCL, while receiving maintenance therapy ( HR=0.075, 95% CI 0.022-0.253, P<0.001) and post-treatment response of VGPR or better ( HR=0.175, 95% CI 0.048-0.638, P=0.008) were independent protective factors for patients with pPCL. Conclusions:In the era of novel agents, hypercalcemia, receiving maintenance therapy, and post-treatment response of VGPR or better are independent prognostic factors for pPCL.

Objective To investigate current management of external auditory canal irrigation among the nurses in otolaryngology in Guangdong Province,and to provide a reference for development and promotion of a standardised procedure.Methods From January to February in 2022,a total of 48 head nurses or nursing backbone in otolaryngology department of 48 hospitals from 21 major cities in Guangdong Province were selected by convenience sampling.A questionnaire proposed by Otolaryngology Nursing Committee of Guangdong Nursing Association was used to investigate the knowledge,operation procedure and training management in external auditory canal irrigation.Results A total of 48 head nurses or nursing backbone responded to the survey.The survey revealed that 34(70.8%)of the participants had mastered the knowledge of external auditory canal irrigation and 38(79.2%)of them had mastered the knowledge on the irrigation indications.In terms of operation procedure,syringe was applied as irrigator in 43(89.6%)hospitals,disposable irrigation needle was applied as flushing connector in 24(50.0%)hospitals,body surface temperature test of operator or patient was carried out in 24(50.0%)hospitals and adjusted flushing pressure was applied according to patients'feedback in 37(77.1%)hospitals.Regarding the training of external auditory canal irritation,35(72.9%)hospitals did not ask patients to sign an informed consent before,29(60.4%)hospitals required qualifications for operator and 45(93.7%)hospitals had the training programs.Conclusions The knowledge of external auditory canal irrigation of otolaryngology nurses in Guangdong province needs to be improved.The management of procedure and training of external auditory canal irrigation shall be standardised.It is suggested that the profession should draw up the external auditory canal irrigation standard,and all hospitals strengthen the management and training in order to promote the standardisation of specialised nursing together.

A new method was developed for simultaneous detection of total 19 kinds of organophosphate esters(OPEs)and their diester metabolites(di-OPEs)in human serum(1.0 mL)and urine(1.5 mL)with low volume of samples.The target compounds were determined using ultra-high performance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS)after acetonitrile liquid-liquid extraction combined with purification using an ENVI-18 solid-phase extraction(SPE)column.OPEs and di-OPEs were separated using a Shim-pack GIST C18 column(100 mm×2.1 mm,2 μm)with a Shim-pack GIST-HP(G)C18 guard column.An electrospray ionization source(ESI)was employed in mass spectrometry analysis,with positive/negative ion mode using the multiple reaction monitoring(MRM).All target compounds were separated within 15 min,and exhibited good linear relationships in the concentration range of 2-100 ng/mL,with correlation coefficients(R2)above 0.994.The method detection limits(MDL)in serum ranged from 0.001 to 0.178 ng/mL and the MDL in urine ranged from 0.001 to 0.119 ng/mL.The recoveries of the analytes spiked in serum and urine matrices at two concentration levels were 30.5%-126.8%,with the relative standard deviations(RSDs)ranged from 1%to 23%.In addition,paired serum and urine samples from 11 patients were analyzed.For all samples tested,the internal standards of OPEs exhibited recoveries between 61%and 114%,whereas the internal standards for di-OPEs had recoveries ranging from 43%to 103%.OPEs and di-OPEs exhibited high detection frequencies in 22 serum and urine samples.Triethyl phosphate(TEP),tributyl phosphate(TBP),tris(2-ethylhexyl)phosphate(TEHP),tris(2-butoxyethyl)phosphate(TBEP),tris(1-chloro-2-propyl)phosphate(TCIPP),triphenyl phosphate(TPHP),tri-m-tolyl-phosphate(TMTP)and 2-ethylhexyl diphenyl phosphate(EHDPP)were universally detected in all serum samples.TCIPP was identified at the highest concentrations(median 0.548 ng/mL)in serum samples.In urine samples,the detection frequency for 12 kinds of target compounds reached 100%.Notably,TBP emerged as the predominant OPE in urine,demonstrating a median concentration of 0.506 ng/mL.Regarding di-OPEs,bis(2-chloroethyl)phosphate(BCEP)and bis(2-butoxyethyl)hydrogen phosphate(BBOEP)were the most abundant in urine,with median concentrations of 6.404 and 2.136 ng/mL,respectively.The total concentrations of OPEs and di-OPEs in serum and urine were 1.580-3.843 ng/mL and 5.149-17.537 ng/mL,respectively.These results not only confirmed the effectiveness of the method in detection of OPEs and di-OPEs in biological matrices,but also revealed the widespread presence of OPE compounds in human body and pointed to potential exposure risks.

Objective To observe the effect of Huayu Xiaozheng Granules on angiogenesis and invasion in trophoblast cells with overexpression of miR-210 and under hypoxia.Methods HTR-8/SVneo cells were cultured in vitro,a miR-210 overexpression model was established by transfection,and a chemical hypoxia model was established by CoCl2 method.The blank group,miR-210 overexpression group,miR-210 overexpression-negative group,miR-210 overexpression+Chinese medicine group,hypoxia+Chinese medicine group and Chinese medicine group in experiment were set up.Western Blot method was used to detect protein expressions of hypoxia-inducible factor 1α(HIF-1α),vascular endothelial growth factor(VEGF),and invasion-associated factors[matrix metalloproteinase 9(MMP-9)and tissue inhibitors of matrix metalloproteinase 1(TIMP-1)]in HTR-8/SVneo cells.Results Compared with the blank group,the protein expression levels of HIF-1α,VEGF,MMP-9,TIMP-1 and MMP-9/TIMP-1 ratio were increased in the miR-210 overexpression group(P＜0.05);compared with the miR-210 overexpression group,the HIF-1α,VEGF,MMP-9,TIMP-1 protein expression levels and MMP-9/TIMP-1 ratio in the miR-210 overexpression-negative group,miR-210 overexpression+Chinese medicine group,hypoxia+Chinese medicine group and Chinese medicine group were all decreased(P＜0.05),and the decrease effects in Chinese medicine group was especially obvious;compared with the miR-210 overexpression+Chinese medicine group,the protein expression levels of HIF-1α,VEGF,MMP-9,TIMP-1 and MMP-9/TIMP-1 ratio in hypoxia+Chinese medicine group and Chinese medicine group were all decreased(P＜0.05);compared with the hypoxia+Chinese medicine group,the above indicators were decreased in the Chinese medicine group(P＜0.05).Conclusion Huayu Xiaozheng Granules can negatively regulate the increased angiogenesis and invasion of trophoblast cells with miR-210 overexpression and under hypoxia,which may be one of the action mechanisms of its treatment for tubal pregnancy.

Objective To monitor the antifungal resistance of clinical isolates of Candida spp.in the East China region.Methods MALDI-TOF MS or molecular methods were used to re-identify the strains collected from January 2018 to December 2022.Antifungal susceptibility testing was performed using the broth microdilution method.The susceptibility test results were interpreted according to the breakpoints of 2022 Clinical and Laboratory Standards Institute(CLSI)documents M27 M44s-Ed3 and M57s-Ed4.Results A total of 3 026 strains of Candida were collected,65.33％of which were isolated from sterile body sites,mainly from blood(38.86％)and pleural effusion/ascites(10.21％).The predominant species of Candida were Candida albicans(44.51％),followed by Candida parapsilosis complex(19.46％),Candida tropicalis(13.98％),Candida glabrata(10.34％),and other Candida species(0.79％).Candida albicans showed overall high susceptibility rates to the 10 antifungal drugs tested(the lowest rate being 93.62％).Only 2.97％of the strains showed dose-dependent susceptibility(SDD)to fluconazole.Candida parapsilosis complex had a SDD rate of 2.61％and a resistance rate of 9.42％to fluconazole,and susceptibility rates above 90％to other drugs.Candida glabrata had a SDD rate of 92.01％and a resistance rate of 7.99％to fluconazole,resistance rates of 32.27％and 48.24％to posaconazole and voriconazole non-wild-type strains(NWT),respectively,and susceptibility rates above 90％to other drugs.Candida tropicalis had resistance rates of 29.55％and 26.24％to fluconazole and voriconazole,respectively,resistance rates of 76.60％and 21.99％to posaconazole and echinocandins non-wild-type strains(NWT),and a resistance rate of 2.36％to echinocandins.Conclusions The prevalence and species distribution of Candida spp.in the East China region are consistent with previous domestic and international reports.Candida glabrata exhibits certain degree of resistance to fluconazole,while Candida tropicalis demonstrates higher resistance to triazole drugs.Additionally,echinocandins resistance has emerged in Candida albicans,Candida glabrata,Candida tropicalis,and Candida parapsilosis.