Objective:To compare the efficacy and safety of crisaborole ointment 2% versus pimecrolimus cream 1% in the treatment of mild to moderate atopic dermatitis in children aged 2 years or older.Methods:A multicenter, randomized, open-label, controlled clinical trial was conducted. A total of 120 pediatric patients aged 2 - 17 years with mild to moderate atopic dermatitis were enrolled from departments of dermatology of 8 hospitals in China between March 2022 and February 2023. The participants were randomly assigned in a 1∶1 ratio to the crisaborole group and the pimecrolimus group, and received the treatment with crisaborole ointment 2% and pimecrolimus cream 1% respectively, twice a day for 4 weeks. Visits were scheduled at baseline/on day 1, as well as on days 8, 15, and 29. The primary efficacy outcome was the percentage of patients achieving the Investigator's Static Global Assessment (ISGA) success (defined as clear [0] or almost clear [1] on the ISGA scale, combined with ≥ 2‐grade improvement from baseline) on day 29. The secondary efficacy outcomes included changes in the Eczema Area and Severity Index (EASI) total scores from baseline to day 29, percentages of patients achieving ISGA improvement (defined as clear [0] or almost clear [1] on the ISGA scale), as well as changes in the Peak Pruritus Numerical Rating Scale (NRS) scores, Dermatology Life Quality Index (DLQI) /Infants' Dermatology Life Quality Index (IDLQI) /Children's Dermatology Life Quality Index (CDLQI) scores, and in the Dermatitis Family Impact (DFI) scores. Drug safety was evaluated according to the incidence of adverse events. Categorical data were compared using the chi-square test. Since measurement data did not follow a normal distribution, the rank sum test was used for comparisons of measurement data between groups.Results:A total of 106 children with mild to moderate atopic dermatitis were included in the per-protocol analysis set, with 52 in the crisaborole group (26 males and 26 females) and 54 in the pimecrolimus group (27 males and 27 females). There were no significant differences in age, disease duration, ISGA and EASI scores at baseline between the two groups (all P > 0.05). On day 29, 22 patients (42.31%) in the crisaborole group and 25 (46.30%) in the pimecrolimus group achieved ISGA success, with no significant difference between the two groups ( χ2 = 0.17, P = 0.68) ; 35 patients (67.31%) in the crisaborole group and 45 (83.33%) in the pimecrolimus group achieved ISGA improvement, also with no significant difference between the two groups ( χ2 = 3.68, P = 0.06) ; additionally, there were no significant differences in the EASI, pruritus NRS, DLQI/IDLQI/CDLQI, or DFI scores between the two groups (all P > 0.05). Adverse reactions to the two topical agents were mainly local reactions such as mild to moderate pain, itching, or worsening of itching, and no obvious systemic adverse reactions occurred. The incidence of drug-related adverse reactions was 46.15% (24 cases) in the crisaborole group and 37.04% (20 cases) in the pimecrolimus group, with no significant difference between the two groups ( χ2 = 0.91, P = 0.34) . Conclusion:The efficacy of crisaborole ointment 2% was comparable to that of pimecrolimus cream 1% in the treatment of mild to moderate atopic dermatitis in children aged ≥ 2 years, and it yielded early and rapid improvement in the quality of life of patients and their families, with good safety and tolerability profiles.

OBJECTIVE: To evaluate the efficacy and safety of a hospital-made resuscitation pack, a Chinese medicinal herbal compound formula designed to enhance recovery in post-bronchoscopy patients. METHODS: In this randomized, single-blind, placebo-controlled clinical trial, eligible patients were randomly assigned 1:1 to either the treatment or control groups. The patients in the treatment group applied the resuscitation pack, which contained aromatic compounded Chinese herbs. The patients in the control group applied a hospital-made, single herb placebo pack. Packs were placed on the Tiantu (CV 22) acupuncture point for 4 h as soon as the bronchoscopy finished. Efficacy indicators, such as recovery time, patients' symptoms including nausea and dizziness, and adverse events (AEs) were observed and compared. The outcome indices were evaluated at baseline, 1 and 24 h after the bronchoscopy. Subgroup analysis was further performed by patients' age and depth of sedation. RESULTS: When applying generalized estimating equations (GEE) to evaluate the intensity of post-bronchoscopy nausea and vomiting, the intensity was lower in the treatment group (163 cases) compared with the control group (162 cases; 95% CI: 0.004, 0.099, P=0.03]. Also, significantly lower intensity of nausea was observed in the 60-70 years of age subgroup (95% CI: 0.029, 0.169, P=0.006) and deep sedation subgroup (95% CI: 0.002, 0.124; P=0.04). There was no significant difference in dizziness between two groups by GEE (95% CI: -0.134, 0.297; P=0.459). In addition, no serious AEs were observed in either group. CONCLUSIONS Our study found that the resuscitation pack markedly improved patients' symptoms by reducing nausea and vomiting after bronchoscopy without AEs, compared with placebo in the perioperative period. (Trial registration No. ChiCTR2000038299).
Humans ; Male ; Middle Aged ; Female ; Bronchoscopy/adverse effects* ; Single-Blind Method ; Aged ; Drugs, Chinese Herbal/adverse effects* ; Treatment Outcome ; Resuscitation ; Adult ; Medicine, Chinese Traditional

Ferroptosis,a novel form of programmed cell death driven by iron-dependent lipid peroxida-tion,plays a crucial role in both disease treatment and microbial control due to its multi-level regulatory mechanisms.It mainly involves iron metabolism,lipid peroxidation,and antioxidant systems.In the field of disease treatment,ferroptosis is regarded as a highly promising therapeutic target because of its key role in autoimmune diseases,cancer,and cardiovascular diseases.This review systematically summarizes the core regulatory factors of ferroptosis,such as glutathione peroxidase 4(GPX4)and long-chain acyl-CoA synthetase 4(ACSL4)and their interaction networks,and deeply explores the application prospects of targeted intervention strategies based on ferroptosis signaling pathways in disease treatment and micro-bial control.Additionally,we also summarize the current issues faced by ferroptosis in practical applica-tions and proposes strategies,such as nanodelivery,improved drug chemical stability and enhanced water solubility to optimize therapeutic efficacy.We aim to provide a theoretical basis and practical guidelines for exploring more targeted treatments using ferroptosis.

Objective To investigate the dosimetric differences in preoperative short-course volumetric modulated arc therapy(VMAT)for rectal cancer using different fluence smoothing(FS)levels in the Monaco Treatment Planning System(Monaco TPS).Methods Twenty rectal cancer patients who received preoperative neoadjuvant short-course VMAT at some hospital from September 2021 to December 2022 were retrospectively selected.Four groups of radiotherapy plans were formulated using the Monaco TPS for each case,which were classified into an off group,a low group,a medium group and a high group based on the FS levels.Then the four groups were compared in terms of the dosimetric parameters,monitor unit and number of the segments in the planning target volume(PTV)and organ at risk(OAR).Statistical analysis was performed using SPSS 27.0 software.Results All the four groups had the doses to the target volume meeting clinical requirements,which had no significant differences in the doses to 5％(D5％)and 95％(D95％)to the target volume and the maximum dose(Dmax),minimum dose(Dmin),mean dose(Dmean)and conformity index(all P＞0.05).Statistical differences were found between the homogeneity indexes of the four groups(P＜0.05),with the medium group behaving the best.The number of the segments rose while the mornitor units decreased siginificantly with the increase of FS levels,with the differences being statistically significant(P＜0.05).There were no significant differences between the V25,V20,V15 and V10 of the small intestine,the V25 and V20 of the bladder and the V15 and V10 of the left and right femur(all P＞0.05).Conclusion In preoperative short-course VMAT for rectal cancer,clinical requirements can be met with different FS levels in the Monaco TPS,and medium-level FS results in optimal overall dose distribution in terms of treatment planning.[Chinese Medical Equipment Journal,2025,46(5):48-53]

Aim To investigate the role of myotubula-rin related protein 7(MTMR7)in the pathogenesis of pulmonary hypertension manifested by pulmonary vas-cular intimal thickening,right ventricular hypertrophy,progressive right heart failure and dysfunction.Meth-ods A total of 40 healthy male C57BL/6J mice and Mtmr7-transgenic(Mtmr7-Tg)mice were divided into the control group,Mtmr7-Tg group,monocrotaline(MCT)group and MCT+Mtmr7-Tg group.Pulmonary artery acceleration time(PAT)and pulmonary artery ejection time(PET)of the pulmonary artery were measured by ultrasound.When the free wall of the right ventricle was separated,the right heart hypertro-phy index(RVHI)was calculated.Pulmonary artery remodeling was observed by immunostaining.Mouse pulmonary artery smooth muscle cells(PASMCs)were cultured in hypoxic environment to induce the prolifer-ation and migration.Results MTMR7 was expressed in pulmonary vessels.Compared to the wild-type mice,Mtmr7-Tg mice showed increased PAT/PET ratio(P＜0.05),reduced RVHI(P＜0.01)after MCT stimu-lus.PASMCs were transfected with adenovirus encond-ing Mtmr7 gene,which inhibited proliferation and mi-gration of PASMCs.After restoring the activity of ERK1/2 by chemerin-9,the proliferation and migra-tion ability of PASMCs was elevated.Conclusions MTMR7 can counteract the growth and mobility of mouse PASMCs induced by hypoxia,thereby comba-ting pulmonary arterial hypertension via reducing ERK1/2 phosphorylation.

OBJECTIVE: To observe the effect of acupuncture on chondrocyte autophagy in rats of knee osteoarthritis (KOA) and explore its underlying mechanisms. METHODS: Forty male SPF-grade SD rats were randomized into a blank group, a model group, a suspension group, an acupuncture group, and a combined therapy group, 8 rats in each one. Except the blank group, KOA model was prepared by the injection with papain. The suspension exercise therapy (10 min each time, three times daily), acupuncture (at "Yanglingquan" [GB34], "Zusanli" [ST36], and "Dubi" [ST35] on the right side, 30 min each intervention, once daily) and the combined therapy (the suspension exercise therapy combined with acupuncture) were delivered in the suspension group, the acupuncture group and the combined therapy group, respectively. The intervention of each group was performed continuously for 6 days, and 4 consecutive weeks, at the interval of 1 day. Before and after intervention, Lequesne MG score was assessed in the rats. After intervention, HE staining was adopted to observe the cartilaginous tissue morphology of the right knee joints, and Mankin score was evaluated; the serum levels of interleukin (IL)-1β, IL-6, and tumor neurosis factor-α (TNF-α) were measured using ELISA; the real-time PCR was provided to determine the mRNA expression of collagen protein type Ⅱ(COL2), collagen protein type Ⅹ (COL10), phosphatidylinositol 3-kinase (PI3K), protein kinase B (Akt), mammalian target of rapamycin (mTOR), and autophagy-regulated protein (Beclin-1) in the cartilaginous tissue of the right knee joint; Western blot was employed to detect the protein expression of PI3K, phosphorylated PI3K (p-PI3K), Akt, phosphorylated Akt (p-Akt), mTOR, phosphorylated mTOR (p-mTOR) and Beclin-1 in the cartilaginous tissue of the right knee joint. RESULTS: Compared with the blank group, the rats in the model group showed the higher Lequesne MG score (P<0.01), thinner cartilage of the right knee, reduced chondrocytes and disordered arrangement, and higher Mankin score (P<0.01). Besides, in the model group, the serum levels of IL-1β, IL-6 and TNF-α were elevated (P<0.01), the mRNA expression of COL2 and Beclin-1 and the protein expression of Beclin-1 decreased (P<0.01), the mRNA expression of COL10, PI3K, Akt and mTOR, and the protein expression of p-PI3K, p-Akt and p-mTOR increased (P<0.01) in the cartilaginous tissue of the right knee joint. Compared with the model group, in the suspension group, the acupuncture group and the combined therapy group, the Lequesne MG scores were reduced (P<0.01), the cartilage of the right knee was thickened, the arrangement of chondrocytes was improved, and the Mankin scores were lower (P<0.01). Besides, in these intervention groups, the serum levels of IL-1β, IL-6 and TNF-α were reduced (P<0.01), the mRNA expression of COL2 and Beclin-1 and the protein expression of Beclin-1 increased (P<0.05, P<0.01), the mRNA expression of COL10, PI3K, Akt and mTOR, and the protein expression of p-PI3K, p-Akt and p-mTOR decreased (P<0.05, P<0.01) in the cartilaginous tissue of the right knee joint. When compared with the suspension group and the acupuncture group, in the combined therapy group, the Lequesne MG score was reduced (P<0.01), and the Mankin score was reduced (P<0.05, P<0.01). Besides, the serum levels of IL-1β, IL-6 and TNF-α were reduced (P<0.05), the mRNA expression of COL2 and Beclin-1 and the protein expression of Beclin-1 increased (P<0.05), the mRNA expression of COL10, PI3K, Akt and mTOR, and the protein expression of p-PI3K, p-Akt and p-mTOR decreased (P<0.05, P<0.01) in the cartilaginous tissue of the right knee joint. CONCLUSION Acupuncture can promote cartilage regeneration of knee joint and autophagy in KOA rats, alleviate inflammation, so as to retard cartilage degeneration, which may be possibly associated with the PI3K/Akt/mTOR signaling pathway.
Animals ; Male ; Acupuncture Therapy ; Proto-Oncogene Proteins c-akt/genetics* ; TOR Serine-Threonine Kinases/genetics* ; Osteoarthritis, Knee/physiopathology* ; Phosphatidylinositol 3-Kinases/genetics* ; Rats ; Signal Transduction ; Rats, Sprague-Dawley ; Chondrocytes/metabolism* ; Humans ; Autophagy ; Acupuncture Points

Macroporous resin adsorption column chromatography, silica gel column chromatography, ODS column chromatography, and semi-preparative high-performance liquid chromatography, combined with analytical methods such as NMR and MS, were employed to separate and identify compounds from the 70% ethanol extract of Ajania purpurea. A total of 30 compounds were isolated and identified, including 13 phenolic acids, 7 coumarins, 2 lignans, 1 flavonoid, 2 sesquiterpenes, 1 steroid, and 4 others. Among them, compounds 1 and 2 were newly discovered compounds, and compounds 4, 6, 8, 12, 14-23, 25, 28, and 30 were isolated from Ajania plants for the first time. Bioactivity screening showed that multiple compounds significantly inhibited the production of nitric oxide in lipopolysaccharide-stimulated RAW264.7 cells in a dose-dependent manner. Furthermore, compound 2 elevated the levels of glutathione in LPS-induced BEAS-2B cells, reduced the expression of pro-inflammatory cytokines such as tumor necrosis factor(TNF)-α, interleukin(IL)-6, and IL-1β, enhanced the mRNA of GPX4, HMOX1, NFE2L2, and enhanced protein levels of GPX4, HO-1, Nrf2, and SLC7A11, demonstrating potential anti-ferroptotic effect.
Mice ; Animals ; Lignans/isolation & purification* ; RAW 264.7 Cells ; Humans ; Nitric Oxide ; Tumor Necrosis Factor-alpha/immunology* ; Drugs, Chinese Herbal/isolation & purification* ; NF-E2-Related Factor 2/metabolism* ; Macrophages/metabolism* ; Interleukin-6/immunology*

Ferroptosis,a novel form of programmed cell death driven by iron-dependent lipid peroxida-tion,plays a crucial role in both disease treatment and microbial control due to its multi-level regulatory mechanisms.It mainly involves iron metabolism,lipid peroxidation,and antioxidant systems.In the field of disease treatment,ferroptosis is regarded as a highly promising therapeutic target because of its key role in autoimmune diseases,cancer,and cardiovascular diseases.This review systematically summarizes the core regulatory factors of ferroptosis,such as glutathione peroxidase 4(GPX4)and long-chain acyl-CoA synthetase 4(ACSL4)and their interaction networks,and deeply explores the application prospects of targeted intervention strategies based on ferroptosis signaling pathways in disease treatment and micro-bial control.Additionally,we also summarize the current issues faced by ferroptosis in practical applica-tions and proposes strategies,such as nanodelivery,improved drug chemical stability and enhanced water solubility to optimize therapeutic efficacy.We aim to provide a theoretical basis and practical guidelines for exploring more targeted treatments using ferroptosis.

Ulcerative colitis（UC） is a chronic non-specific inflammatory bowel disease characterized by inflammation and ulceration of the colonic mucosa and submucosa， and its complex pathogenesis involves immune abnormality， oxidative stress and other factors. The nuclear transcription factor E₂-related factor 2（Nrf2）， encoded by the Nfe212 gene， plays a central role in antioxidant responses. It not only activates various antioxidant response elements such as heme oxygenase-1（HO-1） and quinone oxidoreductase 1（NQO1）， but also enhances the activity of glutathione-S-transferase（GST） and superoxide dismutase 1（SOD1）， effectively eliminating reactive oxygen species（ROS） accumulated in the body， and mitigating oxidative stress-induced damage to intestinal mucosa. In addition， Nrf2 can reduce the release of inflammatory factors and infiltration of immune cells by regulating immune response， cell apoptosis and autophagy pathways， thereby alleviating intestinal inflammation and promoting the repair and regeneration of damaged mucosa. Based on this， this paper reviews the research progress of Chinese materia medica in the prevention and treatment of UC by modulating the Nrf2 signaling pathway. It deeply explores the physiological role of Nrf2， the molecular mechanism of activation， the protective effect in the pathological process of UC， and how active ingredients in Chinese materia medica regulate the Nrf2 signaling pathway through multiple pathways to exert their potential mechanisms. These studies have revealed in depth that Chinese materia medica can effectively combat oxidative stress by regulating the Nrf2 signaling pathway. It can also play a role in anti-inflammatory， promoting autophagy， inhibiting apoptosis， protecting the intestinal mucosal barrier， and promoting intestinal mucosal repair， providing new ideas and methods for the multi-faceted treatment of UC.

Objective:To analyze the liver histological characteristics and clinically related factors in inactive hepatitis B surface antigen (HBsAg) carriers (IHC), and also explore whether antiviral treatment is necessary for IHC, as defined in the 2022 version of the hepatitis B prevention and treatment guidelines.Methods:A multicenter, retrospective cohort study was conducted. Two hundred and thirty-one IHC cases who underwent liver biopsy histopathological examination in nine medical institutions, including Beijing Youan Hospital affiliated with Capital Medical University, from January 2018 to December 2023 were included. General informative data, clinical serological markers, and transient elastography (TE) examination results were collected. Patients were divided into a positive (148 cases) and a negative group (83 cases) according to the results of hepatitis B virus (HBV) DNA detection. The differences in liver pathological inflammatory activity (G) and liver fibrosis stage (S) were analyzed between the two groups to explore the correlation between liver tissue conditions and clinically related factors. Comparsions of normally distributed continwous data, skeukd continuous data, and categorical data between groups are performed using t tests, Mann-Whitney U tests and χ2 tests, respectively. Results:The age of 231 IHC cases was 43 (38, 51) years old, with 95.2% (220/231) aged ≥30 years, and males accounted for 64.9% (150/231). HBsAg and HBV DNA levels were 131.9 (20.8, 400.9) IU/mL and 94.0 (0, 448.5) IU/mL, respectively, of which 35.9% (83/231) were HBV DNA negative (<20 IU/mL). The remarkable proportions of G≥2, S≥2, and liver injury (G≥2 and/or S≥2) in liver tissue were 16.5% (38/231), 29% (67/231), and 35.9% (83/231), respectively. The S≥2 proportion was significantly higher in the HBV DNA-negative group than the positive group (42.2% vs. 21.6%, P<0.001), and it mainly occurred in the population cohort over 30 years old (44.9% vs. 31.0%, P=0.04). The liver stiffness measurement (LSM), aspartate transaminase to platelet ratio index (APRI), and platelet (PLT) were significantly higher in the S≥2 group than the S<2 group ( P<0.05). Conclusion:Clinicians can comprehensively evaluate the degree of liver fibrosis in IHC based on clinical factors such as age, PLT, APRI, and LSM, even if the liver histological results are lacking. The China 2022 version guidelines define that nearly half of IHC has histological indications for antiviral therapy, and liver biopsy and prompt treatment can be recommended.