OBJECTIVE To explore the clinical features， diagnosis， treatment and management measures of multiple immune- related adverse event （irAE） after toripalimab treatment， in order to provide reference for the clinical management of similar cases. METHODS A retrospective analysis was conducted on a post-operative bladder cancer patient who developed various irAEs after toripalimab treatment. The patient’s medical history， laboratory tests， imaging studies， treatment course and outcomes were detailed. The Naranjo scale was used to assess the relationship between the irAEs and toripalimab. RESULTS The patient developed irAEs after receiving toripalimab， such as immune-related myocarditis， liver dysfunction， and myasthenia. According to the Naranjo scale evaluation， it was assessed that these adverse events were related to the administration of toripalimab. After high- dose corticosteroid pulse therapy and immunoglobulin immunomodulation， the patient’s symptoms were effectively relieved， with a improved trend in various physiological indicators and significant improvement in the degree of system/organ damage. CONCLUSIONS Toripalimab may lead to multiple irAEs， including immune-related myocarditis， liver injury， and myasthenia. Early recognition， timely diagnosis， and appropriate treatment of irAE are crucial for improving patient’s prognosis.

Background Coal workers' pneumoconiosis is a serious occupational disease in China. Exhaled volatile organic compounds (VOCs) can serve as the "breath fingerprint" of internal pathological processes, which provides a theoretical basis for exhaled VOCs to be used as potential non-invasive biomarkers for early diagnosis of coal workers' pneumoconiosis. Objective To screen out the characteristic VOCs and important characteristic VOCs of exhaled air in patients with coal workers' pneumoconiosis, and to explore the potential of these VOCs as biomarkers for early non-invasive diagnosis of the disease. Methods In this study, 27 VOCs in the exhaled breath of 22 patients with stage I coal workers' pneumoconiosis, 77 workers exposed to dust, and 92 healthy controls were quantitatively detected by thermal desorption gas chromatography-mass spectrometry (TD-GC-MS). Substances with P<0.05 in univariate analysis and variable importance projection (VIP) >1 in supervised orthogonal partial least squares discriminant analysis (OPLS-DA) model were selected as the characteristic VOCs for early diagnosis of coal workers' pneumoconiosis. Age was included in the LASSO regression model as a covariate to screen out important characteristic VOCs, and the diagnostic performance was evaluated by receiver operating characteristic (ROC) curve. Spearman correlation was further used to explore the correlation between important characteristic VOCs and clinical lung function indicators. Results Through univariate analysis and OPLS-DA modeling, 8 VOCs were selected, including 2-methylpentane, 3-methylpentane, n-hexane, methylcyclopentane, n-heptane, methylcyclohexane, 4-methyl-2-pentanone, and 2-hexanone, in exhaled breath of patients with coal workers' pneumoconiosis. The concentrations of 4 VOCs, including 3-methylpentane, n-hexane, 4-methyl-2-pentanone, and 2-hexanone, showed a decreasing trend with the increase of dust exposure years. By LASSO regression, the important characteristic VOCs of the coal workers' pneumoconiosis group and the dust exposure group were n-hexane, methylcyclohexane and 4-methyl-2-pentanone, and the important characteristic VOCs of the coal workers' pneumoconiosis group and the healthy group were 2-methyl-pentane and 4-methyl-2-pentanone. The ROC analysis showed that the area under the curve (AUC) of n-hexane, methylcyclohexane, and 4-methyl-2-pentanone were 0.969, 0.909, and 0.956, respectively, and the AUC of combined diagnosis was 0.988 and its Youden index was 0.961, suggesting that these results can serve as a valuable reference for further research on early diagnosis. The Correlation analysis found that there was a positive correlation between n-hexane and lung function indicators in the important characteristic VOCs, indicating that it could indirectly reflect the obstruction of lung function ventilation, further proving that important characteristic VOCs have the potential to monitor lung function decline. Conclusion Three important characteristic VOCs selected in this study have the potential to be used as non-invasive biomarkers for early diagnosis and disease monitoring of coal workers' pneumoconiosis, and are worthy of further study and verification.

ObjectiveTo investigate the correlation between the color， odor and volatile components of Paeoniae Radix Alba（PRA） and its processed products， and to examine the effects of different processing methods on the odor and color formation of PRA. MethodThe odor and chromaticity information of PRA， honey chaff-fried PRA and honey bran-fried PRA were identified by electronic nose and colorimeter， and the volatile components in the different processed products of PRA were identified and relatively quantified by headspace gas chromatography-mass spectrometry（HS-GC-MS）， and analyzed using principal component analysis（PCA） and orthogonal partial least squares-discriminant analysis（OPLS-DA）， then the differential key flavor components among the three were screened according to the principles of variable importance in the projection（VIP） value>1 and relative odor activity value（ROAV）≥1. Pearson correlation analysis was used to investigate the association between the differential flavor components and the colorimetric values and electronic nose sensors， respectively. ResultAfter being fried with honey chaff and honey bran， the lightness value（L^*） of PRA decreased， and red-green value（a^*） and yellow-blue value（b^*） increased significantly（P<0.05， P<0.01）. The odor differences were mainly reflected in the S1， S2， S4， S5， S6， S8 and S11 sensors， and the results of PCA of the electronic nose indicated that the odor differences among PRA， honey chaff-fried PRA and honey bran-fried PRA were obvious， among which the overall odor intensity of honey bran-fried PRA was higher than that of honey chaff-fried PRA. A total of 47 volatile components were identified from PRA and its processed products， including 21 for PRA， 36 for honey chaff-fried PRA， and 37 for honey bran-fried PRA. Odor analysis revealed that 12， 24 and 22 volatile components may be the key flavor components in PRA， honey chaff-fried PRA and honey bran-fried PRA， respectively. Correlation analysis showed that the L^* of the decoction pieces was negatively correlated with the content of the Maillard reaction products， the a^* and b^* were positively correlated with the content of the Maillard reaction products， the S1 and S8 sensors were negatively correlated with the content of the Maillard reaction products， and the S2， S4， S5， S6 and S11 sensors were positively correlated with the Maillard reaction products. ConclusionThe color of PRA is deepened after being stir-fried with honey chaff and honey bran， and 5-hydroxymethylfurfural， furfural and other components are generated at the same time， which is in line with the theory of burning aroma strengthens the spleen of stir-fried with honey chaff and honey bran. Honey bran-fried PRA has a stronger Maillard reaction than honey chaff-fried PRA， which makes honey bran-fried PRA with a burnt flavor and a dark yellow color， while honey chaff-fried PRA has a sweet flavor and a bright yellow color.

【Objective】 To study and compare the effects of different storage temperature and time on coagulation factor after cryoprecipitated antihemophilic factor(CAF) melting, and to provide reference for the establishment of industry standards. 【Methods】 From June 2021 to May 2023, a total of 96 bags of CAF were sampled in 4 bags per month, and timely detected in the same month. After the CAF was melted in a 37℃ water bath, the mild to moderate lipemic blood was labeled. Each bag of CAF and two 50 mL transfer bags were divided into two bags and two groups of 20 mL each using a sterile adapter. One group was placed in a 4℃ refrigerator and the other in a 22℃ water bath for 0 h, 4 h, 8 h, 12 h, 24 h and 48 h. Then 2 mL of aseptic sample was taken separately and put into the test tube, and 1mL of sample and 3 mL of buffer were added into the other test tube with the sampling gun and mixed on the machine for testing. The experimental data of 60 bags without mild to moderate lipemic blood cryoprecipitation and coagulation factor were randomly selected and statistically analyzed by SPSS21.0. 【Results】 After melting, CAF was stored for 0 h, 4 h, 8 h, 12 h, 24 h and 48 h to detect the average content and growth rate of coagulation factor in the two groups: 1) Storage at 4℃, factor Ⅷ content was 118.62, 111.57(-5.95%), 105.51(-11.05%), 103.30(-12.92%), 94.35(-20.46%) and 83.25(-29.82%) IU/ bag, respectively; Storage at 22℃, the factor Ⅷ content was 118.62, 112.69(-5.00%), 111.41(-6.08%), 109.01(-8.10%), 101.55(-14.39%) and 92.75(-21.81%) IU/ bag, and the storage results of the two groups were compared. At 24 h at 4℃ and 48 h at 22℃, the content of factor Ⅷ had significant statistical significance(P<0.01), and when stored at 22℃, the decay rate of factor Ⅷ was slower; 2) When stored at 4℃, the content of factor V was 41.19, 41.31(0.29%), 40.52(-1.64%), 40.27(-2.23%), 39.05(-5.19%) and 36.99(-10.21%) IU/ bag, respectively; Stored at 22℃, the factor V content was 41.19, 41.71(1.25%), 42.54(3.28%), 41.94(1.80%), 39.21(-4.80%) and 35.64(-13.48%) IU/ bag, respectively. Comparison of storage results between the two groups showed that the content of factor V was statistically significant(P<0.05) and significantly significant(P<0.01) at 4℃48 h and 22℃48 h, respectively, and the decay rate of factor V was faster when stored at 22℃; 3) When stored at 4℃, the Fbg content was 268.86, 268.17(-0.26%), 262.46(-2.38%), 270.50(0.61%), 267.52(-0.50%) and 261.92(-2.58%) mg/ bag, respectively; Stored at 22℃, the Fbg content was 268.86, 265.86(-1.12%), 264.12(-1.77%), 265.89(-1.11%), 266.04(-1.05%) and 261.04(-2.91%) mg/ bag, respectively. There was no statistical significance between the 2 groups and the original 0 h content in each time period(P>0.05). 【Conclusion】 After CAF melting, coagulation factor decreased with the extension of storage time, especially the decrease of factor Ⅷ, followed by factor V, while Fbg basically unchanged. Comparison between the two groups showed that, factor Ⅷ decay rate is slower, factor V decay rate is faster of storage at 22℃. CAF should be transfused as soon as possible after melting. If the delay is unavoidable, for the delay time less than 12 h, storage at 4℃ is recommended, fot the delay time more than 12 h and less than 24 h, storage at 22℃ is recommended.

Objective: To investigate the antidepressant effects of Yuanzhi (Polygalae Radix, PR) aqueous extract on chronic unpredictable mild stress (CUMS)-induced depression rat models and the underlying mechanisms. Methods: A total of 40 male Sprague Dawley (SD) rats were randomly divided into control, model, low dose of PR (PR-L, 0.5 g/kg), high dose of PR (PR-H, 1 g/kg), and fluoxetine (10 mg/kg) groups, with 8 rats in each group. Except for the rats in control group, those in the other four groups underwent CUMS-induced depression modeling. PR and fluoxetine were administered intragastrically once daily, 30 min prior to the CUMS procedure, for 14 consecutive days until the behavioral tests were performed. After CUMS modeling, the sucrose preference test (SPT), open field test (OFT), novelty-suppressed feeding test (NSFT), forced swim test (FST), and tail suspension test (TST) were employed to assess the pharmacological effects of PR on the mitigation of depressive-like behaviors in rat models. Additionally, the enzyme-linked immunosorbent assay (ELISA) was utilized to quantify the serum levels of tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-1β in the rats. Western blot analysis was also conducted to evaluate the protein expression levels of nuclear factor kappa-B (NF-κB), inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), nucleotide-binding oligomerization domain (NOD)-like receptor family pyrin domain containing 3 (NLRP3), apoptosis-associated speck-like protein containing caspase recruitment domain (ASC), and caspase-1 in the hippocampal tissues of the rats. Immunofluorescence staining was performed to observe the morphological changes in ionized calcium-binding adapter molecule 1positive (Iba-1+) cells in the dentate gyrus (DG) of rats with CUMS-induced depression. Result: (i) Treatment with PR-H and fluoxetine resulted in significant enhancements in both the total distance and time the rats moved during tests (P < 0.01 and P < 0.05, respectively). Post-administration of PR-H and fluoxetine also led to statistically significant increase in sucrose preference among rats (P < 0.05). Besides, PR-L, PR-H, and fluoxetine treatment markedly decreased the latency of ingestion (P < 0.05, P < 0.05, and P < 0.01, respectively). As observed from the FST, PR-L, PR-H, and fluoxetine presented antidepressant effects on rats with CUMS-induced depression, leading to the reduction in time of their immobility (P < 0.05, P < 0.01, and P < 0.01, respectively). The results of TST indicated reduced immobility time in rats receiving PR-H and fluoxetine treatment as well (P < 0.01). (ii) Rats in model group showed an increase in the levels of Iba-1+ microglia in their left and right brains in comparison with control group (P < 0.01). However, such increase was negated post PR treatment (P < 0.01). Treatment with PR-L, PR-H, and fluoxetine considerably reduced the levels of inflammatory factors (TNF-α, IL-1β, and IL-6, P < 0.01). In addition, treatment of PR-L and PR-H effectively counteracted the elevated levels of NLRP3, ASC, and caspase-1, and markedly down-regulated the expression levels of phosphorylated p65 (p-p65), COX-2, and iNOS in rats’ hippocampus (P < 0.01). Conclusion Collectively, these findings indicate that PR exerts an antidepressant effect on rats with CUMS-induced depression partially through the modulation of the NLRP3 and NF-κB signaling pathways.

Objective To explore the drug resistance mechanism and characteristics of carbopenem-resistant pseudo-monas aeruginosa(CRPA)in our hospital.Methods BD phoenix 100 automatic bacterial identification and drug sensitivity an-alyzer was used to identify and detect the drug sensitivity of the strains.The minimum inhibitory concentration(MIC)of ceftazi-dime/acibactam was detected by micro broth dilution method.The modified carbapenem inactivation method(mCIM)and colloi-dal gold immunochromatography were used to detect the carbapenemase phenotype of the strains.The whole genome sequencing was used to detect the carbapenemase resistance gene and ST typing of the screened positive strains.Results A total of 22 strains of clinically isolated CRPA were collected,of which the antibacterial drugs with the lowest resistance rate were ceftidine/avibatan(22.7% ),followed by gentamicin and amikacin(27.3% ),pyracillin/tazobactam(59.09% ),cefuroxime(63.6% ).Ceftazide and aminotransferrane(77.27% ),ciprofloxacin(86.36% ),levofloxacin(95.45% ).There are a total of 5 strains(22.7% )of carbapenems in 22 CRPA by phenotypic detection.The whole genome sequencing results show that 4 strains of ST549 CRPA carry metal β-lactamase IMP-45 and serine β-lactamase OXA-1,OXA-50,one strain is ST245 CRPA carries metal β-lactamase NDM-1,that is,all five CRPA strains produce metal β-lactamase.Conclusion The resistance rate of CRPA to ceftazidime/avibactam is low in our hospital.Carbapenemase-producing is not the main mechanism of CRPA resistance to car-bapenems,while metal β-Lactamase-producing is the main mechanism of CRPA resistance to ceftazidime avibactam.

Objective:To investigate the related factors and prognosis of invasive Klebsiella pneumoniae liver abscess syndrome (IKLAS). Methods:The in-patients diagnosed with Klebsiella pneumoniae liver abscess in the Department of Infectious Diseases, Huashan Hospital, Fudan University from January 2015 to February 2021 were retrospectively enrolled. The patients were divided into IKLAS group and non-IKLAS group according to whether they had IKLAS or not. The clinical data between the two groups were compared, including the prevalence of diabetes mellitus, the details of liver abscess, clinical symptoms such as fever and abdominal pain, as well as laboratory tests such as glycosylated hemoglobin and hemoglobin. Statistical analysis was performed using chi-square test or independent sample t test. Multivariate logistic regression analysis was used to analyze the factors influencing the occurrence of IKLAS. Results:A total of 75 patients with Klebsiella pneumoniae liver abscess were enrolled, including 55 patients (73.33%) in the IKLAS group and 20 patients (26.67%) in the non-IKLAS group. Fifty-two point seven three percent (29/55) of the patients had diabetes mellitus and 12.73%(7/55) of the patients had abdominal pain in the IKLAS group, which were 20.00%(4/20) and 45.00%(9/20) in the non-IKLAS group, respectively, and the differences were both statistically significant ( χ2=6.38 and 7.28, respectively, both P<0.05). Most of liver abscesses were single (50/75, 66.67%), and more likely to occur in the right liver (50/75, 66.67%). The maximum diameter of liver abscess in the IKLAS group was (4.58±2.04) cm, which was smaller than that in the non-IKLAS group ((6.49±3.11) cm), and the difference was statistically significant ( t=2.82, P=0.011). Compared with those in the non-IKLAS group, patients in the IKLAS group had higher glycosylated hemoglobin (8.69%±2.64% vs 6.18%±1.31%) and hemoglobin ((112.25±22.04) g/L vs (100.05±18.59) g/L), and the differences were both statistically significant ( t=-4.25 and -2.21, respectively, both P<0.05). The proportion of patients using antibiotics combined with abscess drainage in the IKLAS group was 38.18%(21/55), and that in the non-IKLAS group was 85.00%(17/20). The difference between the two groups was statistically significant ( χ2=12.86, P<0.001). A total of 16 patients (21 eyes) were diagnosed as endogenous Klebsiella pneumoniae endophthalmitis (EKPE), and all of them were IKLAS patients, and 14 patients underwent monocular/binocular eyeball injection and/or vitrectomy and silicone oil filling. The visual acuity of 13 patients decreased significantly. Multivariate logistic regression analysis showed that complicated with diabetes mellitus was an independent risk factor for IKLAS (odds ratio ( OR)=5.02, 95% confidence interval (95% CI) 1.01 to 25.03, P=0.049). The large diameter of liver abscess was a protective factor for IKLAS ( OR=0.64, 95% CI 0.47 to 0.86, P=0.003). Conclusions:The patients with IKLAS have less abdominal pain, and most of them complicate with diabetes mellitus. Diabetes mellitus is an independent risk factor for the occurrence of IKLAS, while the large diameter of liver abscess is a protective factor. EKPE is associated with poor visual prognosis.

Purpose To investigate the expression and prog-nostic value of programmed death-ligand 1(PD-L1),CD 163 and CD8 in lymphocyte-predominant breast cancer(LPBC),and to analyze the expression of PD-L1,CD 163 and CD8 in primary cancer and corresponding lymph node metastatic cancer.Meth-ods LPBC with complete pathological data were selected.Im-munohistochemical EnVision method was used to detect the ex-pression of PD-L1,CD163 and CD8 in 82 cases of primary cancer and 23 cases of corresponding lymph node metastatic cancer.Their relationships with clinicopathological features and prognosis were analyzed,and the difference of expression be-tween primary cancer and lymph node metastatic cancer.Results The positive rates of PD-L1 in tumor cell(TC)and immune cell(IC)in primary cancer were 25.61％(21/82)and 79.27％(65/82),respectively.The positive rates of TC-PD-L1 in grade Ⅱ and grade Ⅲ were 18.00％(9/50)and 37.50％(12/32),respectively.The expression of TC-PD-L1 was corre-lated with the histological grade(P＜0.05).The positive rates of IC-PD-L1 in tumor maximum diameter ≤2 cm and＞2 cm were 66.67％(18/27)and 85.45％(47/55),respectively.The positive rates of IC-PD-L1 in Ki67≤20％and＞20％were 60.00％(12/20)and 85.48％(53/62),respectively.The ex-pression of IC-PD-L1 was related to tumor maximum diameter and Ki67(P＜0.05).TC-PD-L1 expression was positively correlated with CD8+intratumoral tumor-infiltrating lymphocytes(iTILs)density(r=0.277,P＜0.05),and IC-PD-L1 expression was positively correlated with CD163(r=0.259,P＜0.05).High expression of CD163 was significantly correlated with shorter DFS(P＜0.05).Between primary cancer and lymph node metastatic cancer,the co-expression rates of TC-PD-L1 and IC-PD-L1 were 82.61％(19/23)and 47.82％(11/23),respectively,and the difference was not statistically significant(P＞0.05).There were statistically differences of CD163 expression and CD8+iTILs be-tween primary cancer and lymph node metastatic cancer(P＜0.05).Conclusion PD-L1 expression in primary cancer is as-sociated with poor clinicopathologic features,and high expression of CD163 suggests poor prognosis.There are differences in tumor immune microenvironment between LPBC primary cancer and lymph node metastatic cancer,and re-evaluation of PD-L1 of lymph node metastatic cancer may provide valuable guidance for clinical immunotherapy.

Objective To study EBV infection in nasopharyngeal carcinoma screening population in Guangzhou and analyze the influencing factors.Methods The data of individuals(aged 20 years and above)having EBV antibody of VCA-IgA and NA1-IgA test in Guangzhou Cadre and Talent Health Management Centerwere collected.Current status of EBV infection was studied and its influencing factors were analyzed by logistic regression analysis.Results A total of 55 311 subjects were screened,including 35 429 males(64.05%)and 19,882 females(35.95%).The overall EBV infection rate was 8.00%.There was no significant differences in the infection rate between different sex groups(P>0.05).The infection rate of EBV increased with age,with infection rate of 7.07%in individuals aged 20～39 years,7.86%in those aged 40～59 years,10.11%in those of 60～79 years old,and 10.99%in those aged≥80 years,showing statistical significance(χ2 = 85.487,P<0.01).Logistic regression analysis showed that EBV infection risk increased significantly with advancing age.The odds of EBV infection in individuals aged 40～59 years were 10.6%higher compared to those aged 20～39 years(OR = 1.106,95%CI:1.028～1.190).The odds of EBV infection in individuals aged 60～79 years were 42.2%higher compared to those aged 20～39 years(OR = 1.422,95%CI:1.288～1.569).Furthermore,the odds of EBV infection in individuals aged≥80 years were 53.1%higher compared to those aged 20～39 years(OR = 1.531,95%CI:1.230～1.906).A prior diagnosis of hypertension significantly increased the odds of EBV infection(OR = 1.105,95%CI:1.003～1.218).However,diabetes history exerted no influence on the outcome of EBV infection(P>0.05).Conclusions The overall infection rate of EBV in Guangzhou is 8.00%.Advanced age and hypertension history are the risk factors of EBV.The screening and prevention and control of EBV susceptible people should be strengthened.

Objective:To explore the effects of the immune responses mediated by topological structures of three-dimensional bioprinted scaffolds on hair follicle cycle in mice.Methods:The study was an experimental research. The alginate-gelatin composite hydrogels were printed into scaffolds using a three-dimensional bioprinter and named T45 scaffolds, T60 scaffolds, and T90 scaffolds according to the 3 topological structures of the scaffolds (the rotation angles of the printhead during printing were 45°, 60°, and 90°, respectively), and the morphology of the three scaffolds was observed after cross-linking by naked eyes. Nine 8-week-old female C57BL/6J mice were divided into T45 group, T60 group, and T90 group, according to the random number table, with three mice in each group, and the T45, T60, and T90 scaffolds were subcutaneously implanted on the back of mice, respectively. On post implantation day (PID) 7, the hair growth in the dorsal depilated area of mice was observed, the thickness of the fiber capsule around the scaffolds was observed by hematoxylin-eosin staining, and the expression levels of CD68, bone morphogenetic protein-2 (BMP-2), and tumor necrosis factor (TNF) protein in the tissue surrounding the scaffolds were observed by immunofluorescence staining. The samples of the above experiments were all 3.Results:The topological structures of the three scaffolds were all clear with high fidelity after cross-linking. On PID 7, the hair growth was obvious in the dorsal depilated area of mice in T45 group and T90 group, while hair growth was slow in the scaffold implantation area of mice in T60 group, which was significantly different from that of the unimplanted area. On PID 7, compared with (18±4) μm in T90 group, the thickness of both the fiber capsule around the scaffolds ((39±4) and (55±8) μm) of mice in T45 group and T60 group was significantly increased ( P<0.05); the thickness of the fiber capsule around the scaffolds of mice in T60 group was also significantly increased compared with that in T45 group ( P<0.05). On PID 7, the expression level of CD68 protein in the tissue surrounding the scaffolds of mice in T60 group was significantly higher than the levels in T45 group and T90 group (with both P values <0.05). The expression level of BMP-2 protein in the tissue surrounding the scaffolds of mice in T60 group was significantly higher than the levels in T45 group and T90 group (with both P values <0.05), and the expression level of BMP-2 protein in the tissue surrounding the scaffolds of mice in T45 group was significantly higher than that in T90 group ( P<0.05). The expression level of TNF protein in the tissue surrounding the scaffolds of mice in T60 group was significantly lower than the levels in T45 group and T90 group (with both P values <0.05). Conclusions:Three-dimensional bioprinted scaffolds with different topological structures mediate different degrees of immune responses after being implanted in mice. A moderate immune response promotes hair growth in depilated area of mice, while an excessive immune response results inhibits the hair follicle entering into the anagen phase.