Objective:To summarize the clinical and related characteristics of hospitalized patients with pemphigus, and to analyze their correlations with systemic inflammatory and serological indicators.Methods:A retrospective analysis was conducted on the clinical data from pemphigus patients hospitalized in the Department of Dermatology, Wuhan No.1 Hospital from January 2021 to December 2023. Spearman correlation analysis was performed to assess the correlations between the Pemphigus Disease Area Index (PDAI) scores and systemic immune-inflammation index (SII) , pan-immune-inflammation value (PIV) , serum albumin levels, anti-desmoglein 1/3 (Dsg-1/3) antibody levels, and C-reactive protein (CRP) levels. Linear regression models were used to evaluate the associations of systemic inflammatory and serological indicators with the length of hospital stay and treatment costs. Logistic regression analysis was conducted to analyze the effect of these indicators on the risk of infection in pemphigus patients.Results:A total of 235 pemphigus patients were included (112 males and 123 females) , with ages of 58.12 ± 16.47 years. Among them, 73 patients (31.06%) had pemphigus alone, while 162 (68.94%) had comorbidities including tumors, infections, or hypoalbuminemia. PDAI scores showed significantly positive correlations with SII, PIV, and CRP levels ( r = 0.62, 0.58, 0.50, respectively, all P<0.001) . According to PDAI scores, 164 cases (69.79%) were classified as mild pemphigus, 57 (24.26%) as moderate pemphigus, and 14 (5.96%) as severe pemphigus; compared with the patients with mild pemphigus, those with moderate-to-severe pemphigus had significantly increased SII, PIV, anti-Dsg-1 antibody and CRP levels, but significantly decreased serum albumin levels (all P < 0.05) . Among the 235 patients, 213 were diagnosed with pemphigus vulgaris, 9 with pemphigus erythematosus, 10 with pemphigus foliaceus, and 3 with paraneoplastic pemphigus; serum albumin levels and anti-Dsg-1/3 antibody levels differed significantly among patients with different subtypes of pemphigus (all P < 0.05) . The serum albumin level was significantly associated with the length of hospital stay and treatment costs ( β [95% CI]: -0.729 [-0.946 - -0.512], -0.266 [-0.362 - -0.171], respectively, both P < 0.001) ; furthermore, the serum albumin level was identified as a relevant factor for infections in pemphigus patients ( OR = 0.938, 95% CI: 0.883 - 0.995, P = 0.036) . Conclusion:SII, PIV, CRP, serum albumin, and anti-Dsg-1 antibody levels could reflect the severity of pemphigus to some extent, and the serum albumin level was significantly associated with comorbid infections, length of hospital stay, and treatment costs in hospitalized patients with pemphigus.

Objective:To summarize the clinical and related characteristics of hospitalized patients with pemphigus, and to analyze their correlations with systemic inflammatory and serological indicators.Methods:A retrospective analysis was conducted on the clinical data from pemphigus patients hospitalized in the Department of Dermatology, Wuhan No.1 Hospital from January 2021 to December 2023. Spearman correlation analysis was performed to assess the correlations between the Pemphigus Disease Area Index (PDAI) scores and systemic immune-inflammation index (SII) , pan-immune-inflammation value (PIV) , serum albumin levels, anti-desmoglein 1/3 (Dsg-1/3) antibody levels, and C-reactive protein (CRP) levels. Linear regression models were used to evaluate the associations of systemic inflammatory and serological indicators with the length of hospital stay and treatment costs. Logistic regression analysis was conducted to analyze the effect of these indicators on the risk of infection in pemphigus patients.Results:A total of 235 pemphigus patients were included (112 males and 123 females) , with ages of 58.12 ± 16.47 years. Among them, 73 patients (31.06%) had pemphigus alone, while 162 (68.94%) had comorbidities including tumors, infections, or hypoalbuminemia. PDAI scores showed significantly positive correlations with SII, PIV, and CRP levels ( r = 0.62, 0.58, 0.50, respectively, all P<0.001) . According to PDAI scores, 164 cases (69.79%) were classified as mild pemphigus, 57 (24.26%) as moderate pemphigus, and 14 (5.96%) as severe pemphigus; compared with the patients with mild pemphigus, those with moderate-to-severe pemphigus had significantly increased SII, PIV, anti-Dsg-1 antibody and CRP levels, but significantly decreased serum albumin levels (all P < 0.05) . Among the 235 patients, 213 were diagnosed with pemphigus vulgaris, 9 with pemphigus erythematosus, 10 with pemphigus foliaceus, and 3 with paraneoplastic pemphigus; serum albumin levels and anti-Dsg-1/3 antibody levels differed significantly among patients with different subtypes of pemphigus (all P < 0.05) . The serum albumin level was significantly associated with the length of hospital stay and treatment costs ( β [95% CI]: -0.729 [-0.946 - -0.512], -0.266 [-0.362 - -0.171], respectively, both P < 0.001) ; furthermore, the serum albumin level was identified as a relevant factor for infections in pemphigus patients ( OR = 0.938, 95% CI: 0.883 - 0.995, P = 0.036) . Conclusion:SII, PIV, CRP, serum albumin, and anti-Dsg-1 antibody levels could reflect the severity of pemphigus to some extent, and the serum albumin level was significantly associated with comorbid infections, length of hospital stay, and treatment costs in hospitalized patients with pemphigus.

Objective To investigate the role of lncSIL in transforming growth factor-β1(TGF-β1)-induced alveo-lar epithelial interstitial transformation(EMT)and its related signaling pathways.Methods Western blot was used to detect the effect of lncSIL silencing on the expression of E-cadherin(E-cad),alpha-smooth muscle actin(α-SMA)and Collagen I(Col I)in the process of EMT induced by TGF-β1.LncSIL interacting proteins were ana-lyzed by RNA pulldown.Western blot was used to detect the effect of overexpression or silencing of lncSIL on the expression of its target gene enhancer of zeste homolog 2(EZH2)and its downstream factors P21 and cyclin-de-pendent kinase 6(CDK6).Flow cytometry was used to analyze the effect of lncSIL on cell cycle progression.Re-sults After lncSIL silencing,the expression of α-SMA and Col I increased,the expression of E-cad decreased.RNA pulldown assay showed that EZH2 was the target protein that interacted with lncSIL,and the expression of EZH2 increased after silencing lncSIL,the expression of EZH2 downstream gene P21 decreased,CDK6 increased.Flow cytometry showed that the number of cells in S phase significantly increased.When lncSIL was overexpressed,the expression of EZH2 and CDK6 was down-regulated,the expression of P21 was up-regulated,and the number of S phase cells significantly decreased.Conclusion LncSIL inhibits TGF-β1-induced alveolar epithelial cell mesen-chymal transition by negatively regulating EZH2/P21/CDK6 signaling pathway to inhibit cell cycle progression.

AIM:To explore the efficacy of lenvatinib(Len)in enhancing the therapeutic effects of immune checkpoint inhibitor for hepatocellular carcinoma(HCC)and to delve into its immunomodulatory mechanisms within the tumor microenvironment.METHODS:The effects of various concentrations of Len on the migration of human umbilical vein endothelial cells(HUVECs)and the secretion of CXC chemokine ligand 10(CXCL10)were investigated,and the mechanism by which Len modulates CXCL10 secretion was validated.An orthotopic HCC model was established,and the mice bearing tumors were randomly allocated into 4 groups:PBS group,BMS-202(PD-1/PD-L1 inhibitor)group,Len group,and Len/BMS-202 group.The progression of the orthotopic liver tumors was monitored with small animal in vivo im-aging techniques.On the 13th day after the treatment,mice were sacrificed and tumor tissues were harvested for analysis.Immunofluorescence was employed to identify apoptosis,vascular architecture,and hypoxic status within the tumor tis-sue.The expression levels of proliferation marker Ki67,transforming growth factor-β(TGF-β),and the infiltration de-grees of CD4+T cells and CD8+T cells in the tumor tissue were monitored with immunohistochemistry.The secretion of im-mune factors interferon-γ(IFN-γ),CXCL10 and TGF-α in the mouse serum was quantified with ELISA.Above all data were followed by statistical analysis.RESULTS:(1)Len could facilitate endothelial cell migration within a specific range and potentiated the response of tumor cells to IFN-γ by blocking fibroblast growth factor receptor(FGFR),thereby increasing the secretion of CXCL10 from the tumor cells.(2)Compared with PBS group,tumor growth was slower in all treatment groups,with Len/BMS-202 group showing the most significant inhibition of tumor growth in tumor-bearing mice(P<0.05).(3)Compared with PBS group and monotherapy groups,Len/BMS-202 significantly promoted tumor tissue apoptosis and inhibited tumor cell proliferation(P<0.05).(4)Compared with PBS group and BMS-202 group,both Len group and Len/BMS-202 group manifested a substantial enhancement in pericytes coverage rate(P<0.01),concomitantly showing a marked improvement in hypoxic conditions(P<0.01).(5)Compared with PBS group and monotherapy groups,Len/BMS-202 group showed a significant increase in the infiltration of CD4+T cells and CD8+T cells within the tumor(P<0.01),along with a marked decrease in the expression of TGF-β(P<0.01).(6)Compared with PBS group,all treatment groups collectively induced varying degrees of secretion of IFN-γ,CXCL10 and TGF-α in mouse serum(P<0.05),with Len/BMS-202 group demonstrating the most pronounced effects(P<0.01).CONCLUSION:Lenvatinib may augment the therapeutic efficacy of BMS-202 in HCC by facilitating tumor vascular normalization,alleviating hypoxic conditions,and enhancing the secretion of CXCL10,thereby synergistically activating the tumor immune microenvironment.

Objective:To discuss the protective effect of carnosine(CAR)against oxygen-glucose deprivation/reoxygenation(OGD/R)-induced astrocyte(AS)injury,and to clarify its possible mechanism.Methods:The AS were divided into control group,model group(OGD/R group),OGD/R+CAR group(CAR group),and OGD/R+CAR+AMP-activated protein kinase(AMPK)activator AICAR group(CAR+AICAR group).MTT assay and green cyanine staining method were used to detect the survival rates and green cyanine staining positive rates of the AS in various groups;Annexin V-FITC/PI method and flow cytometry were used to detect the apoptotic rates of the AS in various groups;Western blotting method was used to detect the expression levels of AMPK,phosphorylated AMPK(p-AMPK),mammalian target of rapamycin(mTOR),phosphorylated mTOR(p-mTOR),microtubule-associated protein light chain 3B(LC3B),Beclin-1,and P62 proteins in the AS in various groups;immunofluorescence staining was used to observe the LC3B positive fluorescence intensities in the AS in various groups.Results:Compared with control group,the survival rate and green cyanine staining positive rate of the AS in OGD/R group were decreased(P＜0.01),the apoptotic rate of the AS was increased(P＜0.01),the ratios of p-AMPK/AMPK and LC3B Ⅱ/LC3B Ⅰ and the expression level of Beclin-1 protein were increased(P＜0.01),and the ratio of p-mTOR/mTOR and the expression level of P62 protein were decreased(P＜0.01).Compared with OGD/R group,the survival rate and green cyanine staining positive rate of the AS in CAR group were increased(P＜0.01),the apoptotic rate of the AS was decreased(P＜0.01),the ratios of p-AMPK/AMPK and LC3B Ⅱ/LC3B Ⅰ and the expression level of Beclin-1 protein were decreased(P＜0.01),and the ratio of p-mTOR/mTOR and the expression level of P62 protein were increased(P＜0.01).Compared with CAR group,the survival rate and green cyanine staining positive rate of the AS in CAR+AICAR group were decreased(P＜0.01),the apoptotic rate of the AS was increased(P＜0.01),the ratios of p-AMPK/AMPK and LC3B Ⅱ/LC3B Ⅰ and the expression level of Beclin-1 protein were increased(P＜0.01),and the ratio of p-mTOR/mTOR and the expression level of P62 protein were decreased(P＜0.01).The LC3B immunofluorescence staining results were consistent with the Western blotting results.Conclusion:CAR has the protective effect on injury of the AS induced by OGD/R,and its molecular mechanism may be related to the inhibition of the AMPK/mTOR signaling pathway,thereby inhibiting autophagy.

Objective:To investigate the effects of carnosine(CAR)on the spatial learning and memory abilities of rats with vascular cognitive impairment(VCI),and to explore the roles of the Akt/mTOR pathway and autophagy in this process.Methods:Fifty male Sprague-Dawley(SD)rats were randomly divided into sham-operated(Sham)group,VCI group,VCI+CAR-L group,VCI+CAR-M group,and VCI+CAR-H group.The spatial learning and memory abilities of rats were evaluated by the Morris water maze experiment;Nissl staining was used to detect the damage in the hippocampal CA1 region;the nitroblue tetrazolium and thiobarbituric acid methods were used to measure the activities of superoxide dismutase(SOD)and malondialdehyde(MDA)content in hippocampal tissue;Western Blot was performed to determine the expression of p-Akt,p-mTOR,Beclin-1,and LC3B proteins,and immunofluorescent staining was con-ducted to detect changes in LC3B expression in the CA1 region.SH-SY5Y cells were divided into control group,oxy-gen-glucose deprivation/reperfusion(OGD/R)group,OGD/R+rapamycin(RAPA),OGD/R+CAR(1.2 mmol/L)group,and OGD/R+CAR+RAPA group.Methyl thiazolyl tetrazolium assay was used to detect neuronal survival rate;Western Blot was used to detect the levels of p-mTOR,Beclin-1,and LC3B in neuronal cells;immunofluorescent stai-ning was performed to assess the degree of autophagy.Results:CAR could improve the learning and memory abilities of VCI rats,reduce hippocampal tissue cell damage,and inhibit oxidative stress(P＜0.01).CAR increased the expres-sion of p-Akt,p-mTOR,and p62 proteins(P＜0.01 or P＜0.05)and decreased the expression of Beclin-1 and the ra-tio of LC3B Ⅱ/Ⅰ(P＜0.01 or P＜0.05).CAR significantly increased the survival rate of SH-SY5Y cells after OGD/R(P＜0.01)and inhibited autophagy in hippocampal neurons.Furthermore,the intervention with RAPA counteracted the therapeutic effect of CAR,reduced the survival rate of SH-SY5Y groups(P＜0.01),and enhanced autophagy.Conclusion:CAR can improve rat VCI injury,and its mechanism may involve inhibiting oxidative stress,activating the Akt/mTOR signaling pathway in neuronal cells,and thereby inhibiting excessive autophagy to exert a protective effect.

Objective:To investigate the effects of carnosine(CAR)on the spatial learning and memory abilities of rats with vascular cognitive impairment(VCI),and to explore the roles of the Akt/mTOR pathway and autophagy in this process.Methods:Fifty male Sprague-Dawley(SD)rats were randomly divided into sham-operated(Sham)group,VCI group,VCI+CAR-L group,VCI+CAR-M group,and VCI+CAR-H group.The spatial learning and memory abilities of rats were evaluated by the Morris water maze experiment;Nissl staining was used to detect the damage in the hippocampal CA1 region;the nitroblue tetrazolium and thiobarbituric acid methods were used to measure the activities of superoxide dismutase(SOD)and malondialdehyde(MDA)content in hippocampal tissue;Western Blot was performed to determine the expression of p-Akt,p-mTOR,Beclin-1,and LC3B proteins,and immunofluorescent staining was con-ducted to detect changes in LC3B expression in the CA1 region.SH-SY5Y cells were divided into control group,oxy-gen-glucose deprivation/reperfusion(OGD/R)group,OGD/R+rapamycin(RAPA),OGD/R+CAR(1.2 mmol/L)group,and OGD/R+CAR+RAPA group.Methyl thiazolyl tetrazolium assay was used to detect neuronal survival rate;Western Blot was used to detect the levels of p-mTOR,Beclin-1,and LC3B in neuronal cells;immunofluorescent stai-ning was performed to assess the degree of autophagy.Results:CAR could improve the learning and memory abilities of VCI rats,reduce hippocampal tissue cell damage,and inhibit oxidative stress(P＜0.01).CAR increased the expres-sion of p-Akt,p-mTOR,and p62 proteins(P＜0.01 or P＜0.05)and decreased the expression of Beclin-1 and the ra-tio of LC3B Ⅱ/Ⅰ(P＜0.01 or P＜0.05).CAR significantly increased the survival rate of SH-SY5Y cells after OGD/R(P＜0.01)and inhibited autophagy in hippocampal neurons.Furthermore,the intervention with RAPA counteracted the therapeutic effect of CAR,reduced the survival rate of SH-SY5Y groups(P＜0.01),and enhanced autophagy.Conclusion:CAR can improve rat VCI injury,and its mechanism may involve inhibiting oxidative stress,activating the Akt/mTOR signaling pathway in neuronal cells,and thereby inhibiting excessive autophagy to exert a protective effect.

At present, 2019 novel coronavirus (2019-nCoV) mutations occur frequently, and the current mutation, represented by omicron, has significantly enhanced its transmission and greatly increased the difficulty of prevention and control of Coronavirus Disease 2019 (COVID-19). In order to effectively deal with the epidemic situation of COVID-19, it is urgent to develop accurate, sensitive and field-applicable diversified detection techniques for the mutants. In this review, we introduce the current technical method for 2019-nCoV detection, focus on the application of different method in mutation detection, and analyze their advantages and disadvantages. In addition to the traditional detection techniques such as nucleic acid and immunity, we also discuss the importance of establishing phenotypic correlation detection method such as affinity of 2019-nCoV mutants. It is meaningful for accurately detecting and analyzing the important indexes such as infectivity and pathogenicity of the mutant, as well as for improving the efficiency of epidemic screening and its treatment.

Clinical trials of anti-tumor drugs is not only the important way to develop new drugs, but also the most advanced treatment methods for malignant tumors, bringing survival benefits to patients. There are a large number of new anti-tumor drug clinical trials for lung cancer patients, covering a wide variety of anti-tumor drugs, and with rapid progress and high efficiency of clinical transformation. These trials could not be carried out successfully without the joint efforts of the research team, in which the research nurses also played a role that should not be underestimated. Combined with the work content of clinical research nurses, this paper introduced the post management, role function, core competence and career development prospect of clinical research nurses in the process of carrying out clinical trial of lung cancer drugs in detail. In order to provide reference for more medical institutions to carry out related work, and promote the further development of clinical research nurses to standardization and specialization.
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Antineoplastic Agents/therapeutic use* ; Humans ; Lung Neoplasms/drug therapy*

The Zika virus (ZIKV) and dengue virus (DENV) flaviviruses exhibit similar replicative processes but have distinct clinical outcomes. A systematic understanding of virus–host protein–pro-tein interaction networks can reveal cellular pathways critical to viral replication and disease patho-genesis. Here we employed three independent systems biology approaches toward this goal. First, protein array analysis of direct interactions between individual ZIKV/DENV viral proteins and 20,240 human proteins revealed multiple conserved cellular pathways and protein complexes, including proteasome complexes. Second, an RNAi screen of 10,415 druggable genes identified the host proteins required for ZIKV infection and uncovered that proteasome proteins were crucial in this process. Third, high-throughput screening of 6016 bioactive compounds for ZIKV inhibition yielded 134 effective compounds, including six proteasome inhibitors that suppress both ZIKV and DENV replication. Integrative analyses of these orthogonal datasets pinpoint proteasomes as crit-ical host machinery for ZIKV/DENV replication. Our study provides multi-omics datasets for fur-ther studies of flavivirus–host interactions, disease pathogenesis, and new drug targets.