OBJECTIVES: To elucidate the anti-aging effect of β-sitosterol (BS), an important component in the fruits of Alpinia oxyphylla Miq., in C. elegans and its regulatory effect on ETS-5 gene to modulate ferroptosis. METHODS: C. elegans treated with 10 µg/mL BS were monitored for survival time and changes in body length, motility, and reproductive function. The effect of ETS-5 gene knockdown on survival time of C. elegans was observed, and the changes in fat accumulation and lipid redox homeostasis in the transfected C. elegans were assessed using Oil Red O staining and by detecting MDA levels and the GSH/GSSG ratio. The mRNA expression levels of ferroptosis-related genes (FTN-1, GPX-1 and AAT-9) were detected using qPCR. The effects of BS treatment and ETS-5 knockdown on AAT-9 enzyme activity in C. elegans were examined. The effect of BS on nuclear localization of FEV (the human homolog of ETS-5) was validated in cultured human umbilical venous endothelial cells (HUVECs). RESULTS: Both BS treatment and ETS-5 knockdown significantly prolonged the lifespan, promoted lipid accumulation and reduced lipid peroxidation in C. elegans. ETS-5 knockdown resulted in upregulated expressions of the ferroptosis repressors GPX-1, AAT-9 and FTN-1 and increased the GSH/GSSG ratio in C. elegans. CONCLUSIONS BS inhibits ferroptosis in C. elegans by suppressing the expression of ETS-5 transcription factor and hence the activity of AAT-9 enzyme, a key gene for ferroptosis, which in turn prolongs the lifespan of C. elegans.
Animals ; Caenorhabditis elegans/physiology* ; Ferroptosis/drug effects* ; Alpinia/chemistry* ; Sitosterols/pharmacology* ; Longevity/drug effects* ; Fruit/chemistry* ; Humans

Objective:To analyze the short-term efficacy and safety of tislelizumab combined with neoadjuvant chemotherapy in the treatment of resectable esophageal squamous cell carcinoma (ESCC) .Methods:The clinical data of 56 patients with ESCC who received neoadjuvant therapy combined with surgical resection in the Department of Thoracic Surgery, Affiliated Hospital of Guangdong Medical University from April 2021 to October 2023 were collected. According to the different preoperative neoadjuvant therapy methods, the patients were divided into neoadjuvant chemotherapy combined with immunotherapy group (chemoimmunization group, n=24) and neoadjuvant chemotherapy group (chemotherapy group, n=32). The postoperative tumor regression grade, objective response rate (ORR), disease control rate (DCR), pathological complete response (pCR) rate, major pathological remssion (MPR) rate, R0 resection rate, perioperative indicators, and security were compared between the two groups. Results:In chemoimmunization group, the tumor regression grade was better than that in chemotherapy group, with a statistically significant difference ( Z=9.39, P=0.025). The ORR and the DCR were 75.00% (18/24) and 91.67% (22/24) in chemoimmunization group, and 46.88% (15/32) and 65.62% (21/32) in chemotherapy group, with statistically significant differences ( χ2=4.48, P=0.034; χ2=5.21, P=0.022). The R0 resection rate was 87.50% (21/24) in chemoimmunization group, which was higher than that of the chemotherapy group [59.38% (19/32) ], with a statistically significant difference ( χ2=5.31, P=0.021). The pCR rate and MPR rate were 29.17% (7/24) and 54.17% (13/24) in chemoimmunization group, and 6.25% (2/32) and 28.12% (9/32) in chemotherapy group, there was no statistically significant difference in pCR rate ( χ2=3.78, P=0.052), but there was a statistically significant difference in MPR rate ( χ2=3.89, P=0.048). The interval between the end of neoadjuvant treatment and the start of surgery was (42.71±8.29) days in chemoimmunization group, and (42.25±8.03) days in chemotherapy group. The intraoperative blood loss of patients was (215.54±57.85) ml in chemoimmunization group, and (229.65±57.74) ml in chemotherapy group. The operation time of patients was (293.52±37.50) minutes in chemoimmunization group, and (295.31±37.66) minutes in chemotherapy group. The postoperative hospitalization time of patients was (17.90±3.49) days in chemoimmunization group, and (18.42±3.82) days in chemotherapy group, all with no statistically significant differences ( t=0.21, P=0.835; t=0.90, P=0.370; t=0.18, P=0.861; t=0.52, P=0.603). In terms of postoperative complications, there was no statistically significant difference in the total incidence of postoperative complications between the two groups [62.50% (15/24) vs. 84.38% (27/32), χ2=0.59, P=0.440]. The main adverse drug reactions in the two groups included decreased white blood cell count, nausea and vomiting, liver dysfunction, pruritus, hypothyroidism, etc. Most of them were grade 1-2, 3 cases were grade 3, and no grade 4 adverse reactions occurred. The total incidence of adverse reactions was 62.50% (15/24) in chemoimmunization group, and 65.62% (21/32) in chemotherapy group, with no statistically significant difference ( χ2=0.06, P=0.809) . Conclusion:For the preoperative neoadjuvant therapy of resectable ESCC, the combination of tislelizumab and chemotherapy has better short-term efficacy and better safety than the single chemotherapy scheme, which can improve the surgical efficacy.

Objective:To analyze the clinical features of adult deficiency of adenosine deaminase 2 (DADA2) with neurological impairment.Methods:The clinical data of an adult DADA2 patient with concurrent neurological damage who visited the Department of Neurology, Mindong Hospital Affiliated to Fujian Medical University on September 18, 2023 were retrospectively analyzed. The clinical studies or case reports related to adult DADA2 with nervous system involvement from Pubmed, CNKI, and Wanfang databases were retrieved, and the clinical characteristics of adult DADA2 with neurological damage were summarized. The clinical data of children with nervous system involvement in the same study cohorts were also collected, and the clinical features of DADA2 between adults and children were compared.Results:The patient was a 30-year-old male, mainly presenting with manifestations of livedo reticularis, stroke and spastic paraplegia. Genetic testing showed a compound heterozygous mutation in the adenosine deaminase 2 ( ADA2) gene, and brain MRI showed lacunar infarcts in the right basal ganglia and thalamus, hypertrophic inferior olivary degeneration. The literature review found that a total of 22 adult DADA2 patients with neurological damage have been reported, with a onset age of 25 (19, 29) years. Stroke was the most common feature of neurological involvement in patients with this disease (17/22, 77.3%), followed by cranial nerve damage (7/22, 31.8%) and limb nerve damage (8/22, 36.4%). After the treatment with tumor necrosis factor (TNF) inhibitors, the condition of 17/20 patients remained stable or improved. Compared with pediatric DADA2 patients with concurrent neurological damage, the incidence of fever [12/22(54.5%) vs 48/59(81.4%)], arthritis [6/22(27.3%) vs 34/59(57.6%)], and hematological abnormalities [4/22(18.2%) vs 28/60(46.7%)] in adult DADA2 patients was significantly reduced, and the difference was statistically significant (χ 2=5.998, 5.907, 5.489, respectively, all P<0.05). Conclusions:Adult DADA2 with concurrent neurological damage generally onset in early adulthood, mainly manifested as stroke, and may also be accompanied by peripheral nerve damage. Adult patients have fewer systemic symptoms than children, and timely treatment with TNF inhibitors can lead to better outcomes.

Objective To evaluate the effect of salicylic acid on skin barrier function and the efficacy of salicylic acid combined with flumetasone ointment for the treatment of atopic dermatitis (AD).Methods Sixtyfour patients with AD (including 31 males and 33 females) aged 18 to 58 years were recruited into the present study.Four lesional areas of similar size and severity were selected at the similar body sites of both sides of each patient,and randomly classified into four groups to be topically treated with compound flumetasone ointment (containing 0.02％ flumetasone and 3％ salicylic acid,compound flumetasone group),flumetasone 0.02％ ointment (flumetasone group),salicylic acid 3％ ointment (salicylic acid group) and vehicle (control group),respectively;two normal skin areas were chosen from apparently normal skin on the similar body sites of both sides of each patient and topically treated with salicylic acid 3％ ointment (salicylic acid group) and vehicle (control group) respectively.All of these preparations were applied twice a day for 3 weeks.Transepidermal water loss (TEWL) was measured by a Tewameter MPA580 (Courage & Khazaka,Germany) at the baseline as well as on week 1,2 and 3 after initiation of treatment.Symptom and sign scores were evaluated before and after the treatment.Meanwhile,two normal skin areas were selected on bilateral forearm of 30 healthy controls and treated with 3％ salicylic acid ointment (salicylic acid group) and vehicle (control group) respectively twice a day for 3 weeks,and TEWL was measured before treatment as well as on week 1 and 3 after initiation of treatment.Results In the healthy controls,TEWL value showed no significant difference between the salicylic acid group and control group at any of these time points.As far as the lesional skin was concerned,no statistical difference was observed in TEWL value at the baseline between the four groups ((34.26 ± 20.82) vs.(33.02 ±16.71) vs.(34.16 ± 18.03) vs.(33.81 ± 17.11) g· m-2· h-1,P ＞ 0.05),but significant difference was noted after treatment (repeated measurement data analysis of variance,F =39.57,P ＜0.01),with the TEWL value being (22.38 ± 16.16),(17.04 ± 12.74),and (15.34 ± 13.13) g·m-2·h-1 respectively in the compound flumetasone group on week 1,2 and 3,(24.63 ± 17.08),(20.37 ± 9.53),(19.06 ± 9.17) g·m-2·h-1 respectively in the flumetasone group,(26.49 ± 8.59),(21.91 ± 8.46),(21.20 ± 9.38) g·m-2·h-1 respectively in the salicylic acid group,and (29.80 ± 12.48),(26.16 ± 8.31),(25.52 ± 6.05) g·m-2·h-1 respectively in the control group.In detail,the decrease in TEWL value was stronger in the compound flumetasone group than in the flumetasone group on week 1,2,and 3 (all P ＜0.05),in the salicylic acid group than in the control group (P ＜0.05 or 0.01),but similar between the flumetasone group and salicylic acid group.In non-lesional skin,the salicylic acid group showed a more intense decrease in TEWL value compared with the control group on week 2 and 3 (both P ＜0.05).Both the cure rate and response rate were significantly higher in the compound flumetasone group than in the flumetasone group (53.1％ vs.34.4％,x2 =4.57,P＜0.05;83.1％ vs.64.1％,x2 =6.90,P＜0.01).Conclusions The salicylic acid 3％ ointment shows a reparative effect on skin barrier in patients with AD,and the compound flumetasone ointment is superior to the flumetasone ointment in the treatment of AD.