Objective This study aimed to investigate whether photodynamic therapy(PDT)with methylene blue(MB)as a photosensitizer can induce ferroptosis in melanoma cells and its potential mechanisms.Methods The paraffin sections of malignant melanoma patients(5 cases)and malignant melanoma patients with lymph node metastasis(5 cases)were collected.Prussian blue,TUNEL and immunohistochemical staining were performed to compare the degree of ferroptosis between the two groups.CCK-8 assay and scratch assay were used to detect the cytotoxic effect of methylene blue and methylene-blue-mediated photodynamic therapy on B16F10 under different treatment conditions and the effect of cell migration ability.The expression of ferroptosis-related proteins(glutathione peroxidase 4,GPX4、solute carrier family 7 member 11,SLC7A11)in B16F10 cells was detected by Western blot.The expression levels of intracellular malondialdehyde(MDA)and GSH/GSSG were detected by microplate reader.The expression levels of reactive oxygen species(ROS),Fe2+and lipid peroxide(LPO)in B16F10 cells were detected by flow cytometry.Results Compared with melanoma cells transferred to lymph nodes,the non-metastatic group had a higher degree of ferroptosis and a lower expression level of SLC7A11.The cytotoxicity of MB and MB-PDT on B16F10 was dose-dependent(P＜0.000 1).The results of scratch assay showed that MB-PDT inhibited the migration ability of B16F10 cells(P＜0.001).Compared with the control group,after MB-PDT treatment,the expression levels of GPX4,SLC7A11 and GSH/GSSG were decreased(P＜0.05),and the expression levels of ROS,Fe2+,LPO and MDA were increased(P＜0.05)in B16F10 cells.Pretreatment with Ferrostatin-1,an inhibitor of ferroptosis,inhibited MB-PDT-induced cytotoxicity and ferroptosis in B16F10 cells(P＜0.05).Conclusion MB-PDT can induce ferroptosis of melanoma cells by inhibiting SLC7A11 expression,thereby inhibiting the progression of melanoma.

Objective Neurological disorders,constitute the majority of acupuncture-treated ailments.By critically examining a comprehensive selection of high-quality clinical randomized controlled trials(RCTs)from both domestic and international sources,we aimed to uncover the prevailing hot research topic and potential future directions in acupuncture therapy for these conditions.Methods Four databases,including PubMed,Web of science,Cochrane Library and EMBASE were searched.The search period is set from the establishment of each database to November 30,2023.And the search content was RCTs of acupuncture for neurological diseases classified as Ⅰ and Ⅱ by the Chinese Academy of Sciences were extracted.Key aspects extracted included annual publication volume,journals,disease types,outcomes,conclusions,acupuncture methods and control groups.Results A total of 81 high-quality RCTs were identified,revealing a consistent annual publication trend of acupuncture for neurological disorders.Key journals contributing to this research were Cephalalgia,Clinical Rehabilitation and Clinical Journal Of Pain,etc.The studies predominantly focused on migraine and sequela of apoplexy with migraine days/frequency and Ashworth scale and its modifications as commonly used primary outcome indicators,respectively.Overall,there were 73 RCTs that concluded that acupuncture for neurologic disorders were effective,8 were ineffective.The acupuncture methods were diverse,encompassing acupuncture,individualized acupuncture and transcutaneous electrical nerve stimulation,etc.The control measures were also varied,featuring sham acupuncture,sham-acupoint and micro-needle,etc.Conclusion With the development of acupuncture RCTs,their international influence has expanded.Research has shifted from validation of effectiveness to exploration of mechanisms,and despite the expansion of the disease spectrum of acupuncture,acupuncture trials have yet to be regulated and standardized,and the assessment of acupuncture efficacy remains controversial and challenging for the discipline.It is recommended to promote multi-center cooperation and strengthen the training of trialists etc.to provide more high-quality clinical evidence.

Objective This study aimed to investigate whether photodynamic therapy(PDT)with methylene blue(MB)as a photosensitizer can induce ferroptosis in melanoma cells and its potential mechanisms.Methods The paraffin sections of malignant melanoma patients(5 cases)and malignant melanoma patients with lymph node metastasis(5 cases)were collected.Prussian blue,TUNEL and immunohistochemical staining were performed to compare the degree of ferroptosis between the two groups.CCK-8 assay and scratch assay were used to detect the cytotoxic effect of methylene blue and methylene-blue-mediated photodynamic therapy on B16F10 under different treatment conditions and the effect of cell migration ability.The expression of ferroptosis-related proteins(glutathione peroxidase 4,GPX4、solute carrier family 7 member 11,SLC7A11)in B16F10 cells was detected by Western blot.The expression levels of intracellular malondialdehyde(MDA)and GSH/GSSG were detected by microplate reader.The expression levels of reactive oxygen species(ROS),Fe2+and lipid peroxide(LPO)in B16F10 cells were detected by flow cytometry.Results Compared with melanoma cells transferred to lymph nodes,the non-metastatic group had a higher degree of ferroptosis and a lower expression level of SLC7A11.The cytotoxicity of MB and MB-PDT on B16F10 was dose-dependent(P＜0.000 1).The results of scratch assay showed that MB-PDT inhibited the migration ability of B16F10 cells(P＜0.001).Compared with the control group,after MB-PDT treatment,the expression levels of GPX4,SLC7A11 and GSH/GSSG were decreased(P＜0.05),and the expression levels of ROS,Fe2+,LPO and MDA were increased(P＜0.05)in B16F10 cells.Pretreatment with Ferrostatin-1,an inhibitor of ferroptosis,inhibited MB-PDT-induced cytotoxicity and ferroptosis in B16F10 cells(P＜0.05).Conclusion MB-PDT can induce ferroptosis of melanoma cells by inhibiting SLC7A11 expression,thereby inhibiting the progression of melanoma.

Objective Neurological disorders,constitute the majority of acupuncture-treated ailments.By critically examining a comprehensive selection of high-quality clinical randomized controlled trials(RCTs)from both domestic and international sources,we aimed to uncover the prevailing hot research topic and potential future directions in acupuncture therapy for these conditions.Methods Four databases,including PubMed,Web of science,Cochrane Library and EMBASE were searched.The search period is set from the establishment of each database to November 30,2023.And the search content was RCTs of acupuncture for neurological diseases classified as Ⅰ and Ⅱ by the Chinese Academy of Sciences were extracted.Key aspects extracted included annual publication volume,journals,disease types,outcomes,conclusions,acupuncture methods and control groups.Results A total of 81 high-quality RCTs were identified,revealing a consistent annual publication trend of acupuncture for neurological disorders.Key journals contributing to this research were Cephalalgia,Clinical Rehabilitation and Clinical Journal Of Pain,etc.The studies predominantly focused on migraine and sequela of apoplexy with migraine days/frequency and Ashworth scale and its modifications as commonly used primary outcome indicators,respectively.Overall,there were 73 RCTs that concluded that acupuncture for neurologic disorders were effective,8 were ineffective.The acupuncture methods were diverse,encompassing acupuncture,individualized acupuncture and transcutaneous electrical nerve stimulation,etc.The control measures were also varied,featuring sham acupuncture,sham-acupoint and micro-needle,etc.Conclusion With the development of acupuncture RCTs,their international influence has expanded.Research has shifted from validation of effectiveness to exploration of mechanisms,and despite the expansion of the disease spectrum of acupuncture,acupuncture trials have yet to be regulated and standardized,and the assessment of acupuncture efficacy remains controversial and challenging for the discipline.It is recommended to promote multi-center cooperation and strengthen the training of trialists etc.to provide more high-quality clinical evidence.

Objective:To compare the effects of standard cognitive behavioral therapy for insomnia (CBT-I) and enhanced cognitive behavioral therapy for insomnia(CBT-I Plus) in patients with chronic insomnia disorder comorbid anxiety or depressive symptoms.Methods:This prospective study included 148 patients with chronic insomnia disorder and anxiety/depression symptoms who were treated at the Sleep Disorder clinic of Shanghai Mental Health Center between July 2020 and August 2023. Participants (56 males, 92 females; aged 18-65 years, mean age 35.08±10.30 years) were randomly assigned in a 1∶2 ratio to the CBT-I group ( n=54) or CBT-I Plus group ( n=94). The CBT-I Plus group received additional treatments targeting anxiety and depressive symptoms. Treatment lasted 8 weeks, with assessment conducted at baseline, weeks 2, 4, and 8. Depression severity was measured using the 17-item Hamilton Depression Rating Scale (HAMD 17), anxiety severity with the Hamilton Anxiety Scale (HAMA), and sleep quality with the Pittsburgh Sleep Quality Index (PSQI). Paired sample t-tests were used to evaluate within-group changes, repeated-measures ANOVA compared treatment effects between groups, and ANCOVA was employed to adjust for confounding variables. Results:Significant reductions in PSQI, HAMD 17, and HAMA scores were observed in both groups after treatment: CBT-I group: PSQI ((14.15±2.54) vs. (7.50±3.35), t=13.25), HAMD 17 ((14.70±4.09) vs. (7.40±4.61), t=9.33), and HAMA ((14.94±4.11) vs. (5.56±3.67), t=12.38) (all P<0.001).CBT-I Plus group: PSQI ((14.87±3.01) vs. (7.19±3.86), t=18.75), HAMD 17 ((16.84±3.91) vs. (6.84±4.79), t=17.42), and HAMA ((15.57±3.93) vs. (6.10±4.57), t=18.39) (all P<0.001). After adjusting for HAMD 17 scores and medication use, no statistically significant between-group differences were observed in changes in PSQI, HAMD 17, and HAMA scores ( P>0.05). A significant time-by-group interaction was found for the PSQI daytime dysfunction subscale ( F=4.87, P<0.01). Conclusion:Both CBT-I and CBT-I Plus improve sleep and emotional symptoms in patients with chronic insomnia disorder and comorbid anxiety/depression symptoms. However, CBT-I Plus has no significant advantages over standard CBT-I. Further studies are needed to refine the timing and content of interventions.

Objective:To compare the effects of standard cognitive behavioral therapy for insomnia (CBT-I) and enhanced cognitive behavioral therapy for insomnia(CBT-I Plus) in patients with chronic insomnia disorder comorbid anxiety or depressive symptoms.Methods:This prospective study included 148 patients with chronic insomnia disorder and anxiety/depression symptoms who were treated at the Sleep Disorder clinic of Shanghai Mental Health Center between July 2020 and August 2023. Participants (56 males, 92 females; aged 18-65 years, mean age 35.08±10.30 years) were randomly assigned in a 1∶2 ratio to the CBT-I group ( n=54) or CBT-I Plus group ( n=94). The CBT-I Plus group received additional treatments targeting anxiety and depressive symptoms. Treatment lasted 8 weeks, with assessment conducted at baseline, weeks 2, 4, and 8. Depression severity was measured using the 17-item Hamilton Depression Rating Scale (HAMD 17), anxiety severity with the Hamilton Anxiety Scale (HAMA), and sleep quality with the Pittsburgh Sleep Quality Index (PSQI). Paired sample t-tests were used to evaluate within-group changes, repeated-measures ANOVA compared treatment effects between groups, and ANCOVA was employed to adjust for confounding variables. Results:Significant reductions in PSQI, HAMD 17, and HAMA scores were observed in both groups after treatment: CBT-I group: PSQI ((14.15±2.54) vs. (7.50±3.35), t=13.25), HAMD 17 ((14.70±4.09) vs. (7.40±4.61), t=9.33), and HAMA ((14.94±4.11) vs. (5.56±3.67), t=12.38) (all P<0.001).CBT-I Plus group: PSQI ((14.87±3.01) vs. (7.19±3.86), t=18.75), HAMD 17 ((16.84±3.91) vs. (6.84±4.79), t=17.42), and HAMA ((15.57±3.93) vs. (6.10±4.57), t=18.39) (all P<0.001). After adjusting for HAMD 17 scores and medication use, no statistically significant between-group differences were observed in changes in PSQI, HAMD 17, and HAMA scores ( P>0.05). A significant time-by-group interaction was found for the PSQI daytime dysfunction subscale ( F=4.87, P<0.01). Conclusion:Both CBT-I and CBT-I Plus improve sleep and emotional symptoms in patients with chronic insomnia disorder and comorbid anxiety/depression symptoms. However, CBT-I Plus has no significant advantages over standard CBT-I. Further studies are needed to refine the timing and content of interventions.

Objective:Glucorticoid therapy has the potential to mitigate immunogical effect of naxitamab. Ketamine is an anesthetic medica-tion and cause weak or shallow breathing. This article is to analyze the effect of modified conditioning regimen with substitution re-mifentanil for ketamine and without glucorticoid therapy on adverse events associated with naxitamab. Methods:Clinical data with naxit-amab infusion under modified conditioning regimen in Sun Yat-sen University Cancer Center between June 2023 and June 2024 were re-trieved to analyze adverse events and risk factors. Results:Overall,seventeen patients underwent 201 infusions. The most frequent adverse events were as follows:neurological pain (all grades) 93.0％,hypertension 55.7％,hypotension 34.8％,respectively. Bronchospasm and hyp-oxia were seen in 3.0％ and 10.9％ infusions,respectively. Fever occurred less frequently in the second cycle of infusion. No patients suspen-ded infusion due to severe adverse event. Conclusions:The infusion of naxitamab is tolerable under the modified conditioning regimen and adverse event is less than expected and controllable.

Objective To monitor the susceptibility of clinical isolates to antimicrobial agents in healthcare facilities in major regions of China in 2023.Methods Clinical isolates collected from 73 hospitals across China were tested for antimicrobial susceptibility using a unified protocol based on disc diffusion method or automated testing systems.Results were interpreted using the 2023 Clinical & Laboratory Standards Institute (CLSI) breakpoints.Results A total of 445199 clinical isolates were collected in 2023,of which 29.0％ were gram-positive and 71.0％ 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) (MRSA,MRSE and MRCNS) was 29.6％,81.9％ and 78.5％,respectively.Methicillin-resistant strains showed significantly higher resistance rates to most antimicrobial agents than methicillin-susceptible strains (MSSA,MSSE and MSCNS).Overall,92.9％ of MRSA strains were susceptible to trimethoprim-sulfamethoxazole and 91.4％ of MRSE strains were susceptible to rifampicin.No vancomycin-resistant strains were found.Enterococcus faecalis had 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 93.1％ in the isolates from children and and 95.9％ in the isolates from adults.The resistance rate to carbapenems was lower than 15.0％ for most Enterobacterales species except for Klebsiella,22.5％ and 23.6％ of which were resistant to imipenem and meropenem,respectively .Most Enterobacterales isolates were highly susceptible to tigecycline,colistin and polymyxin B,with resistance rates ranging from 0.6％ to 10.0％.The resistance rate to imipenem and meropenem was 21.9％ and 17.4％ for Pseudomonas aeruginosa,respectively,and 67.5％ and 68.1％ for Acinetobacter baumannii,respectively.Conclusions Increasing resistance to the commonly used antimicrobial agents is still observed in clinical bacterial isolates.However,the prevalence of important crabapenem-resistant organisms such as crabapenem-resistant K.pneumoniae,P.aeruginosa,and A.baumannii showed a slightly decreasing trend.This finding suggests that strengthening bacterial resistance surveillance and multidisciplinary linkage are important for preventing the occurrence and development of bacterial resistance.

Objective:Glucorticoid therapy has the potential to mitigate immunogical effect of naxitamab. Ketamine is an anesthetic medica-tion and cause weak or shallow breathing. This article is to analyze the effect of modified conditioning regimen with substitution re-mifentanil for ketamine and without glucorticoid therapy on adverse events associated with naxitamab. Methods:Clinical data with naxit-amab infusion under modified conditioning regimen in Sun Yat-sen University Cancer Center between June 2023 and June 2024 were re-trieved to analyze adverse events and risk factors. Results:Overall,seventeen patients underwent 201 infusions. The most frequent adverse events were as follows:neurological pain (all grades) 93.0％,hypertension 55.7％,hypotension 34.8％,respectively. Bronchospasm and hyp-oxia were seen in 3.0％ and 10.9％ infusions,respectively. Fever occurred less frequently in the second cycle of infusion. No patients suspen-ded infusion due to severe adverse event. Conclusions:The infusion of naxitamab is tolerable under the modified conditioning regimen and adverse event is less than expected and controllable.