Objective:To investigate the association between photodynamic diagnosis(PDD)and treatment efficacy of 5-aminolevu-linic acid(ALA)photodynamic therapy(PDT)in patients with cutaneous squamous cell carcinoma in situ(cSCCis).Methods:A pro-spective cohort study was conducted among the patients with cSCCis who underwent ALA-PDT in Department of Dermatology,Huashan Hospital,Fudan University,from January 2020 to November 2024.All patients were diagnosed with cSCCis based on biopsy,and invasive squamous cell carcinoma was excluded.Clinical information was collected and PDD was performed before treatment,and the patients were divided into moderate fluorescence group and strong fluorescence groups based on fluorescence intensity.All patients received six sessions of PDT treatment at an interval of 1-2 weeks.The primary endpoint was the initial complete clearance rate at 3 months after the last treatment session,and secondary endpoints were the sustained complete clearance rate at 12 months after the last treatment session and treatment failure rate.The multivariate regression analysis,the survival curves,and the Cox regression analysis were used to investigate the association between PDD fluorescence intensity and treatment efficacy,as well as other influencing factors for treatment efficacy.Results:Compared with the strong fluorescence group,the moderate fluorescence group had significantly lower initial complete clearance rate[57.14%(8/14)vs.93.33%(28/30),odds ratio OR=0.100,P=0.010]and sustained complete clearance rate[42.86%(6/14)vs.76.67%(23/30),OR=0.230,P=0.030)].The multivariate regression analysis showed that moderate fluores-cence was an independent risk factor for initial complete clearance(OR=0.030,P=0.030).The moderate fluorescence group had a significantly higher treatment failure rate than the strong fluorescence group[57.14%(8/14)vs.23.33%(7/30),P=0.030].The survival analysis and the Cox regression analysis showed that moderate fluo-rescence was an independent risk factor for PDT treatment failure(hazard ratio=3.040,P=0.048).There were no significant differences in adverse reactions between the two groups.Conclusion:PDD fluorescence intensity can predict the efficacy of ALA-PDT in patients with cSCCis.Moderate fluorescence indicates a higher risk of treatment failure,which can help to guide clinicians in develop-ing individualized treatment strategies.

Objective:To investigate the expression pattern,clinical significance,and the regulatory role of 2',5'-oligoadenylate synthetase 1(OAS1)in the proliferation of pancreatic ductal adenocarcinoma(PDAC)cells.Methods:Public databases such as Gene Expression Omnibus(GEO)and The Cancer Genome Atlas(TCGA)were used to analyze the expression of OAS1 in pancreatic cancer tissues.Immunohistochemical staining was applied to validate the expression level of OAS1 in PDAC tissue microarrays,and the association between OAS1 expression level and the prognosis of patients was analyzed.Real-time fluorescence quantitative PCR was performed to examine the expression level of OAS1 mRNA in different PDAC cell lines.CCK-8 assay and colony formation assay was used to assess the effect of OAS1 on the proliferation of PDAC cells after OAS1 silencing in Patu-8988 and PDC0034 cells by siRNA treatment.Further,Gene Set enrichment analysis(GSEA)was performed to screen for possible molecular mechanism of the regulatory role of OAS1 in PDAC.Cell viability and cholesterol level was analyzed after treatment with mTOR signaling activator MHY1485 in OAS1-silenced Patu-8988 and PDC0034 cells in order to verify the underlying mechanism of the regulatory role of OAS1 in PDAC cell proliferation.Results:Database analysis showed significant upregulation of OAS1 expression in pancreatic cancer tissues(P<0.05).Immunohistochemical staining results from PDAC tissue microarray showed that OAS1 expression was significantly upregulated in PDAC tissues compared with the paired paracancerous tissues,and high OAS1 expression was associated with poor prognosis(P<0.05).Real-time fluorescence quantitative PCR and Western blotting analysis show that OAS1 expression was higher in PDAC cells lines compared with normal ductal cells of the pancreas.The proliferative activity of PDAC cells decreased significantly after OAS1 silencing in Patu-8988 and PDC0034 cells(P<0.001).GSEA results indicated that OAS1 may affect PDAC cell proliferation through mTOR signaling pathway and cholesterol metabolism associated pathway.The mTOR signaling pathway may be inhibited and the total cellular cholesterol decreased after OAS1 silencing.Treatment with mammalian target of rapamycin(mTOR)activator MHY1485 partially reversed the inhibitory effect of OAS1 silencing on the proliferation and cholesterol metabolism of PDAC cells.Conclusion:OAS1 expression is upregulated in PDAC tumor tissues and cells and is associated with poor prognosis.OAS1 may promote the proliferation of pancreatic cancer cells by enhancing cholesterol metabolism through activation of the mTOR signaling pathway.

Background and purpose:Actinic keratosis(AK)is a precancerous condition with the potential to develop into cutaneous squamous cell carcinoma.5-Aminolevulinic acid photodynamic therapy(ALA-PDT)has emerged as a new treatment option for AK due to its high clearance rates and non-invasive cosmetic advantages.However,its efficacy in treating Olsen grade 3 AK,characterized by hyperkeratosis,remains controversial.This study aimed to investigate the efficacy and safety of ALA-PDT in treating Olsen grade 3 AK and to identify factors influencing treatment outcomes.Methods:A total of 38 patients with Olsen grade 3 AK who visited the Department of Dermatology,Huashan Hospital,Fudan University,between January 2020 and July 2023 underwent four consecutive sessions of ALA-PDT and were followed up for one year post-treatment(ethics number:2019-491).All patients met the inclusion and exclusion criteria.Treatment efficacy was assessed by the initial complete clearance(ICC)at 3 months and the sustained complete clearance(SCC)at 12 months after treatment.Baseline clinical and pathological characteristics were collected.Univariate and multivariate logistic regression analyses were performed to explore risk factors for treatment failure in Olsen grade 3 AK patients receiving ALA-PDT.Subgroup analyses were conducted to further investigate risk factors associated with treatment resistance and recurrence.This study was registered on Chinese Clinical Trial Registry(chiCTR1800019213).The Strengthening the Reporting of Observational Studies in Epidemiology(STROBE)checklist was followed for this study.Results:A total of 38 patients were included in this study,including 8 in the case group and 29 in the control group.One patient was lost to follow-up 6 months after treatment.At 3 months post-treatment,86.84%of patients achieved ICC(33/38).At the 12-month follow-up,87.88%of the patients who achieved ICC maintained SCC(29/33).No serious adverse reactions were reported during treatment and follow-up.Multivariate logistic regression analysis indicated that lesions located in multiple anatomical subunits was an independent risk factor for treatment failure(P=0.02,OR=28.43).Subgroup analysis confirmed that this factor was independently associated with treatment resistance(P=0.03,OR=97.54).Conclusion:ALA-PDT is effective and safe for treating Olsen grade 3 AK,offering a non-invasive treatment option for these patients.However,patients with lesions located in multiple anatomical subunits are more prone to treatment failure,warranting increased clinical attention in this population.

Objective:To investigate the expression pattern,clinical significance,and the regulatory role of 2',5'-oligoadenylate synthetase 1(OAS1)in the proliferation of pancreatic ductal adenocarcinoma(PDAC)cells.Methods:Public databases such as Gene Expression Omnibus(GEO)and The Cancer Genome Atlas(TCGA)were used to analyze the expression of OAS1 in pancreatic cancer tissues.Immunohistochemical staining was applied to validate the expression level of OAS1 in PDAC tissue microarrays,and the association between OAS1 expression level and the prognosis of patients was analyzed.Real-time fluorescence quantitative PCR was performed to examine the expression level of OAS1 mRNA in different PDAC cell lines.CCK-8 assay and colony formation assay was used to assess the effect of OAS1 on the proliferation of PDAC cells after OAS1 silencing in Patu-8988 and PDC0034 cells by siRNA treatment.Further,Gene Set enrichment analysis(GSEA)was performed to screen for possible molecular mechanism of the regulatory role of OAS1 in PDAC.Cell viability and cholesterol level was analyzed after treatment with mTOR signaling activator MHY1485 in OAS1-silenced Patu-8988 and PDC0034 cells in order to verify the underlying mechanism of the regulatory role of OAS1 in PDAC cell proliferation.Results:Database analysis showed significant upregulation of OAS1 expression in pancreatic cancer tissues(P<0.05).Immunohistochemical staining results from PDAC tissue microarray showed that OAS1 expression was significantly upregulated in PDAC tissues compared with the paired paracancerous tissues,and high OAS1 expression was associated with poor prognosis(P<0.05).Real-time fluorescence quantitative PCR and Western blotting analysis show that OAS1 expression was higher in PDAC cells lines compared with normal ductal cells of the pancreas.The proliferative activity of PDAC cells decreased significantly after OAS1 silencing in Patu-8988 and PDC0034 cells(P<0.001).GSEA results indicated that OAS1 may affect PDAC cell proliferation through mTOR signaling pathway and cholesterol metabolism associated pathway.The mTOR signaling pathway may be inhibited and the total cellular cholesterol decreased after OAS1 silencing.Treatment with mammalian target of rapamycin(mTOR)activator MHY1485 partially reversed the inhibitory effect of OAS1 silencing on the proliferation and cholesterol metabolism of PDAC cells.Conclusion:OAS1 expression is upregulated in PDAC tumor tissues and cells and is associated with poor prognosis.OAS1 may promote the proliferation of pancreatic cancer cells by enhancing cholesterol metabolism through activation of the mTOR signaling pathway.

Background and purpose:Actinic keratosis(AK)is a precancerous condition with the potential to develop into cutaneous squamous cell carcinoma.5-Aminolevulinic acid photodynamic therapy(ALA-PDT)has emerged as a new treatment option for AK due to its high clearance rates and non-invasive cosmetic advantages.However,its efficacy in treating Olsen grade 3 AK,characterized by hyperkeratosis,remains controversial.This study aimed to investigate the efficacy and safety of ALA-PDT in treating Olsen grade 3 AK and to identify factors influencing treatment outcomes.Methods:A total of 38 patients with Olsen grade 3 AK who visited the Department of Dermatology,Huashan Hospital,Fudan University,between January 2020 and July 2023 underwent four consecutive sessions of ALA-PDT and were followed up for one year post-treatment(ethics number:2019-491).All patients met the inclusion and exclusion criteria.Treatment efficacy was assessed by the initial complete clearance(ICC)at 3 months and the sustained complete clearance(SCC)at 12 months after treatment.Baseline clinical and pathological characteristics were collected.Univariate and multivariate logistic regression analyses were performed to explore risk factors for treatment failure in Olsen grade 3 AK patients receiving ALA-PDT.Subgroup analyses were conducted to further investigate risk factors associated with treatment resistance and recurrence.This study was registered on Chinese Clinical Trial Registry(chiCTR1800019213).The Strengthening the Reporting of Observational Studies in Epidemiology(STROBE)checklist was followed for this study.Results:A total of 38 patients were included in this study,including 8 in the case group and 29 in the control group.One patient was lost to follow-up 6 months after treatment.At 3 months post-treatment,86.84%of patients achieved ICC(33/38).At the 12-month follow-up,87.88%of the patients who achieved ICC maintained SCC(29/33).No serious adverse reactions were reported during treatment and follow-up.Multivariate logistic regression analysis indicated that lesions located in multiple anatomical subunits was an independent risk factor for treatment failure(P=0.02,OR=28.43).Subgroup analysis confirmed that this factor was independently associated with treatment resistance(P=0.03,OR=97.54).Conclusion:ALA-PDT is effective and safe for treating Olsen grade 3 AK,offering a non-invasive treatment option for these patients.However,patients with lesions located in multiple anatomical subunits are more prone to treatment failure,warranting increased clinical attention in this population.

Objective:To analyze measurement results of serum allergen-specific immunoglobulin E (IgE) in patients with eczema/dermatitis.Methods:A retrospective analysis was conducted on serum allergen-specific immunoglobulin E (IgE) levels in 3 051 patients with eczema/dermatitis, who visited the allergy clinic of Huashan Hospital from April 1, 2021 to March 31, 2022. The serum allergen-specific IgE level was detected by using the Phadia allergen detection system, and positive rates of allergens were calculated to determine common inhaled allergens and food allergens in patients with eczema/dermatitis. Comparisons of enumeration data between groups were performed by chi-square test.Results:Among the 3 051 patients with eczema/dermatitis, there were 1 412 with atopic dermatitis and 1 639 were other eczema/dermatitis. Detection of serum allergen-specific IgE showed that 1 629 (53%) patients were positive for allergens, and the number of positive allergen-specific IgEs in each patient was 3.0 ± 1.6. The top 3 common inhaled allergens in patients with eczema/dermatitis were Dermatophagoides farinae (904/1 522, 59%) , Dermatophagoides pteronyssinus (891/1 513, 59%) and Alternaria alternata (206/1 068, 19%) , and the top 3 common food allergens were shrimps (251/1 432, 18%) , egg white (165/992, 17%) and cow milk (149/994, 15%) . Among the 3 051 patients, 25 (1%) were aged < 2 years, 571 (19%) aged 2 - 12 years, 285 (9%) aged 12 - 18 years, and 2 170 (71%) were aged > 18 years. The most common food allergens were both egg white in the age groups of < 2 years and 2 -12 years (77%, 37%, respectively) , and were both shrimps in the age groups of 12 - 18 years and > 18 years (31%, 17%, respectively) . Dermatophagoides pteronyssinus and Dermatophagoides farina were the top 2 common inhaled allergens in all age groups, with the positive rate ranging from 36% to 84%; in addition, the positive rate of molds was relatively high in the age group of 2 - 12 years (mold mixture: 37%; Alternaria alternata: 27%) . From April 2021 to March 2022, the positive rate of outdoor allergens ranged from 10% to 15% among outpatients in every month; the positive rates of tree pollen and grass pollen increased from April 2021, and peaked in October 2021. The patients with atopic dermatitis showed a significantly increased positive rate of allergens (73%) compared with those with other eczema/dermatitis (37%, χ2 = 389.36, P<0.001) , and the rank of common allergens in the patients with atopic dermatitis was basically the same as that in those with eczema/dermatitis. Conclusions:The common allergens were Dermatophagoides farina, Dermatophagoides pteronyssinus and Alternaria alternata in the patients with eczema/dermatitis. Food allergy was more common in infant patients, and inhalation allergy was more common in child, adolescent and adult patients. The positive rate of allergen-specific IgEs was markedly higher in the patients with atopic dermatitis than in those with other eczema/dermatitis.

Ischemic stroke is a severe disorder resulting from acute cerebral thrombosis. Here we demonstrated that post-ischemic treatment with ciclopirox olamine (CPX), a potent antifungal clinical drug, alleviated brain infarction, neurological deficits and brain edema in a classic rat model of ischemic stroke. Single dose post-ischemic administration of CPX provided a long-lasting neuroprotective effect, which can be further enhanced by multiple doses administration of CPX. CPX also effectively reversed ischemia-induced neuronal loss, glial activation as well as blood-brain barrier (BBB) damage. Employing quantitative phosphoproteomic analysis, 130 phosphosites in 122 proteins were identified to be significantly regulated by CPX treatment in oxygen glucose deprivation (OGD)-exposed SH-SY5Y cells, which revealed that phosphokinases and cell cycle-related phosphoproteins were largely influenced. Subsequently, we demonstrated that CPX markedly enhanced the AKT (protein kinase B, PKB/AKT) and GSK3 (glycogen synthase kinase 3) phosphorylation in OGD-exposed SH-SY5Y cells, and regulated the cell cycle progression and nitric oxide (NO) release in lipopolysaccharide (LPS)-induced BV-2 cells, which may contribute to its ameliorative effects against ischemia-associated neuronal death and microglial inflammation. Our study suggests that CPX could be a promising compound to reduce multiple ischemic injuries; however, further studies will be needed to clarify the molecular mechanisms involved.

Objective To investigate the trend in incidence, causative drugs, clinical types and treatment of drug eruption. Methods Clinical data were collected from 922 inpatients with drug eruption in Huashan Hospital, Fudan University from January 2009 to December 2013, and analyzed retrospectively. Results From 2009 to 2013, the percentage of inpatients with drug eruption among all inpatients in the Department of Dermatology in a given year varied from 9.45% to 10.01%, and the percentage of inpatients with severe drug eruption among inpatients with drug eruption from 17.45% to 28.24%. Of the 922 cases, 371 (40.2%)were caused by single drugs, and 551 (59.8%)by multiple drugs. Among the 371 cases of drug eruption caused by single drugs, the top five causative drugs were traditional Chinese medicine(72 cases), cephalosporins(38 cases), amoxicillin(27 cases), antipyretic analgesics(26 cases)and tetanus antitoxin (24 cases)in 278 cases of non-severe drug eruption, antiepileptic agents (33 cases), allopurinol (28 cases), antipyretic analgesics (7 cases), cephalosporins (6 cases)and traditional Chinese medicine (6 cases)in 93 cases of severe drug eruption. Of the 922 patients, 422 (45.8%)presented with maculopapular eruption, 259 (28.1%)with urticaria, 135(14.6%)with Stevens-Johnson syndrome, 49(5.3%)with toxic epidermal necrolysis, 33(3.6%)with drug reaction with eosinophilia and systemic symptoms (DRESS), and 7 (0.8%)with acute generalized exanthematous pustulosis (AGEP). A total of 791 (85.8%)patients with drug eruption received glucocorticoid treatment. The dose of glucocorticoids was(47.61 ± 12.07)mg prednisone equivalent per day in 550 patients with non-severe drug eruption, and (73.10 ± 18.23)mg prednisone equivalent per day in 221 patients with severe drug eruption. Totally, 110 (11.0%) patients with drug eruption were treated with combined intravenous immunoglobulin (IVIG)because of poor response to glucocorticoids alone. Of 224 patients with severe drug eruption, only 2 (0.9%)died. Conclusions Carbamazepine and allopurinol are the main causative drugs for severe drug eruption, while traditional Chinese medicine is the first causative drug for non-severe drug eruption. From 2009 to 2013, the annual mortality of severe drug eruption decreased considerably.