This article systematically reviews the role and relationship of heme oxygenase （HO） in the pathogenesis of metabolic associated fatty liver disease （MAFLD） and discusses the biological function of HO， its expression in the liver， its association with lipid metabolism， and its regulatory role in inflammatory reaction and oxidative stress， in order to reveal the potential therapeutic targets and mechanism of HO in MAFLD and provide new perspectives and directions for future treatment strategies.

Osteoporosis is a prevalent skeletal condition characterized by reduced bone mass and strength, leading to increased fragility. Buqi-Tongluo (BQTL) decoction, a traditional Chinese medicine (TCM) prescription, has yet to be fully evaluated for its potential in treating bone diseases such as osteoporosis. To investigate the mechanism by which BQTL decoction inhibits osteoclast differentiation in vitro and validate these findings through in vivo experiments. We employed MTS assays to assess the potential proliferative or toxic effects of BQTL on bone marrow macrophages (BMMs) at various concentrations. TRAcP experiments were conducted to examine BQTL's impact on osteoclast differentiation. RT-PCR and Western blot analyses were utilized to evaluate the relative expression levels of osteoclast-specific genes and proteins under BQTL stimulation. Finally, in vivo experiments were performed using an osteoporosis model to further validate the in vitro findings. This study revealed that BQTL suppressed receptor activator of NF-κB ligand (RANKL)-induced osteoclastogenesis and osteoclast resorption activity in vitro in a dose-dependent manner without observable cytotoxicity. The inhibitory effects of BQTL on osteoclast formation and function were attributed to the downregulation of NFATc1 and c-fos activity, primarily through attenuation of the MAPK, NF-κB, and Calcineurin signaling pathways. BQTL's inhibitory capacity was further examined in vivo using an ovariectomized (OVX) rat model, demonstrating a strong protective effect against bone loss. BQTL may serve as an effective therapeutic TCM for the treatment of postmenopausal osteoporosis and the alleviation of bone loss induced by estrogen deficiency and related conditions.
Animals ; NFATC Transcription Factors/genetics* ; Drugs, Chinese Herbal/pharmacology* ; Ovariectomy ; Osteoclasts/metabolism* ; Female ; Osteogenesis/drug effects* ; Rats, Sprague-Dawley ; Rats ; NF-kappa B/genetics* ; Osteoporosis/genetics* ; Signal Transduction/drug effects* ; Bone Resorption/genetics* ; Cell Differentiation/drug effects* ; Humans ; RANK Ligand/metabolism* ; Mitogen-Activated Protein Kinases/genetics* ; Transcription Factors

Here, we report a previously unrecognized syndromic neurodevelopmental disorder associated with biallelic loss-of-function variants in the RBM42 gene. The patient is a 2-year-old female with severe central nervous system (CNS) abnormalities, hypotonia, hearing loss, congenital heart defects, and dysmorphic facial features. Familial whole-exome sequencing (WES) reveals that the patient has two compound heterozygous variants, c.304C>T (p.R102*) and c.1312G>A (p.A438T), in the RBM42 gene which encodes an integral component of splicing complex in the RNA-binding motif protein family. The p.A438T variant is in the RRM domain which impairs RBM42 protein stability in vivo. Additionally, p.A438T disrupts the interaction of RBM42 with hnRNP K, which is the causative gene for Au-Kline syndrome with overlapping disease characteristics seen in the index patient. The human R102* or A438T mutant protein failed to fully rescue the growth defects of RBM42 ortholog knockout ΔFgRbp1 in Fusarium while it was rescued by the wild-type (WT) human RBM42. A mouse model carrying Rbm42 compound heterozygous variants, c.280C>T (p.Q94*) and c.1306_1308delinsACA (p.A436T), demonstrated gross fetal developmental defects and most of the double mutant animals died by E13.5. RNA-seq data confirmed that Rbm42 was involved in neurological and myocardial functions with an essential role in alternative splicing (AS). Overall, we present clinical, genetic, and functional data to demonstrate that defects in RBM42 constitute the underlying etiology of a new neurodevelopmental disease which links the dysregulation of global AS to abnormal embryonic development.
Female ; Animals ; Mice ; Humans ; Child, Preschool ; Intellectual Disability/genetics* ; Heart Defects, Congenital/genetics* ; Facies ; Cleft Palate ; Muscle Hypotonia

Objective:To investigate the value of contrast-enhanced ultrasound (CEUS) as a preoperative planning strategy for lymphaticovenous anastomosis (LVA) in improving the quality of LVA and the outcome of short-term limb volume reduction in patients with secondary upper limb lymphedema.Methods:Patients with breast cancer-related upper extremity lymphedema who underwent LVA at the Department of General Surgery Cancer Center Division of Breast Surgery of Zhejiang Provincial People’s Hospital from August 2021 to August 2023 were enrolled retrospectively. According to whether preoperative ultrasound lymphography was performed, the patients were divided into CEUS assisted group and control group. In the CEUS assisted group, preoperative CEUS lymphography combined with high-frequency ultrasound color Doppler imaging was utilized for precise localization of lymphatic vessels and recipient veins, as well as surgical target planning for LVA. In the control group, preoperative indocyanine green lymphography was employed to guide surgical exploration. Mann-Whitney U test was used to compare the number of LVA surgical exploration incisions per limb and the number of successful anastomoses per limb between the two groups. The success rate of anastomosis (total number of successful anastomoses/total number of surgical exploration incisions) was compared by the chi-square test. The duration of single anastomosis, mean arm circumference, and the difference between preoperative and postoperative mean arm circumference were compared by independent sample t-test. Paired-sample t-test was used to compare the improvement of the mean arm circumference of the operated limb of the two groups after 3 months of follow-up. P < 0.05 was considered statistically significant. Results:A total of 47 female patients were enrolled, including 27 patients in the CEUS assisted group, with an average age of (57.1±9.0) years and a median edema course of 2 years. There were 20 cases in the control group, with an average age of (58.1±9.6) years and a median duration of edema of 2 years. The CEUS group, compared with the control group, exhibited a higher number of surgical exploration incisions per limb [6.0 (4.0, 7.0) cases vs. 5.0 (3.0, 6.0) cases], a greater number of successful anastomoses per limb [5.0 (3.0, 6v0) cases vs. 3.0 (2.0, 3.0) cases], and a significantly increased overall success rate of anastomosis [82.8% (125/151) vs. 61.4% (54/88)]. Additionally, there was a significant increase in the preoperative and postoperative mean arm circumference difference [(6.2±3.3) cm vs. (3.9±1.9) cm]. The duration of single anastomosis was significantly shortened [(57.4±16.0) min vs. (92.8±18.5) min], with statistically significant differences observed in all comparisons (all P < 0.05). The preoperative and postoperative mean arm circumference were compared between the CEUS group [(31.4±4.6) cm vs. (25.3±4.7) cm] and the control group [(31.3±4.3) cm vs. (27.5±3.8) cm], respectively, with statistically significant differences observed in both groups (both P < 0.01). Conclusion:CEUS lymphography, as a preoperative planning strategy for LVA, can significantly increase the number and success rate of LVA anastomosis in patients with secondary upper limb lymphedema, shorten the duration of single anastomosis, and improve the short-term effect of limb volume reduction after LVA.

Objective To explore the activation of tumor necrosis factor-α(TNF-α)signaling pathway and the expressions of the associated inflammatory factors in NPHP1-defective renal tubular epithelial cells.Methods A human proximal renal tubular cell(HK2)model of lentivirus-mediated NPHP1 knockdown(NPHP1KD)was constructed,and the expressions of TNF-α,p38,and C/EBPβ and the inflammatory factors CXCL5,CCL20,IL-1β,IL-6 and MCP-1 were detected using RT-qPCR,Western blotting or enzyme-linked immunosorbent assay.A small interfering RNA(siRNA)was transfected in wild-type and NPHP1KDHK2 cells,and the changes in the expressions of TNF-α,p38,and C/EBPβ and the inflammatory factors were examined.Results NPHP1KDHK2 cells showed significantly increased mRNA expressions of TNF-α,C/EBPβ,CXCL5,IL-1β,and IL-6(P<0.05),protein expressions of phospho-p38 and C/EBPβ(P<0.05),and IL-6 level in the culture supernatant(P<0.05),and these changes were significantly blocked by transfection of cells with siRNA-C/EBPβ(P<0.05).Conclusion TNF-α signaling pathway is activated and its associated inflammatory factors are upregulated in NPHP1KDHK2 cells,and C/EBPβ may serve as a key transcription factor to mediate these changes.

Objective To explore the activation of tumor necrosis factor-α(TNF-α)signaling pathway and the expressions of the associated inflammatory factors in NPHP1-defective renal tubular epithelial cells.Methods A human proximal renal tubular cell(HK2)model of lentivirus-mediated NPHP1 knockdown(NPHP1KD)was constructed,and the expressions of TNF-α,p38,and C/EBPβ and the inflammatory factors CXCL5,CCL20,IL-1β,IL-6 and MCP-1 were detected using RT-qPCR,Western blotting or enzyme-linked immunosorbent assay.A small interfering RNA(siRNA)was transfected in wild-type and NPHP1KDHK2 cells,and the changes in the expressions of TNF-α,p38,and C/EBPβ and the inflammatory factors were examined.Results NPHP1KDHK2 cells showed significantly increased mRNA expressions of TNF-α,C/EBPβ,CXCL5,IL-1β,and IL-6(P<0.05),protein expressions of phospho-p38 and C/EBPβ(P<0.05),and IL-6 level in the culture supernatant(P<0.05),and these changes were significantly blocked by transfection of cells with siRNA-C/EBPβ(P<0.05).Conclusion TNF-α signaling pathway is activated and its associated inflammatory factors are upregulated in NPHP1KDHK2 cells,and C/EBPβ may serve as a key transcription factor to mediate these changes.

Objective:To investigate the value of contrast-enhanced ultrasound (CEUS) as a preoperative planning strategy for lymphaticovenous anastomosis (LVA) in improving the quality of LVA and the outcome of short-term limb volume reduction in patients with secondary upper limb lymphedema.Methods:Patients with breast cancer-related upper extremity lymphedema who underwent LVA at the Department of General Surgery Cancer Center Division of Breast Surgery of Zhejiang Provincial People’s Hospital from August 2021 to August 2023 were enrolled retrospectively. According to whether preoperative ultrasound lymphography was performed, the patients were divided into CEUS assisted group and control group. In the CEUS assisted group, preoperative CEUS lymphography combined with high-frequency ultrasound color Doppler imaging was utilized for precise localization of lymphatic vessels and recipient veins, as well as surgical target planning for LVA. In the control group, preoperative indocyanine green lymphography was employed to guide surgical exploration. Mann-Whitney U test was used to compare the number of LVA surgical exploration incisions per limb and the number of successful anastomoses per limb between the two groups. The success rate of anastomosis (total number of successful anastomoses/total number of surgical exploration incisions) was compared by the chi-square test. The duration of single anastomosis, mean arm circumference, and the difference between preoperative and postoperative mean arm circumference were compared by independent sample t-test. Paired-sample t-test was used to compare the improvement of the mean arm circumference of the operated limb of the two groups after 3 months of follow-up. P < 0.05 was considered statistically significant. Results:A total of 47 female patients were enrolled, including 27 patients in the CEUS assisted group, with an average age of (57.1±9.0) years and a median edema course of 2 years. There were 20 cases in the control group, with an average age of (58.1±9.6) years and a median duration of edema of 2 years. The CEUS group, compared with the control group, exhibited a higher number of surgical exploration incisions per limb [6.0 (4.0, 7.0) cases vs. 5.0 (3.0, 6.0) cases], a greater number of successful anastomoses per limb [5.0 (3.0, 6v0) cases vs. 3.0 (2.0, 3.0) cases], and a significantly increased overall success rate of anastomosis [82.8% (125/151) vs. 61.4% (54/88)]. Additionally, there was a significant increase in the preoperative and postoperative mean arm circumference difference [(6.2±3.3) cm vs. (3.9±1.9) cm]. The duration of single anastomosis was significantly shortened [(57.4±16.0) min vs. (92.8±18.5) min], with statistically significant differences observed in all comparisons (all P < 0.05). The preoperative and postoperative mean arm circumference were compared between the CEUS group [(31.4±4.6) cm vs. (25.3±4.7) cm] and the control group [(31.3±4.3) cm vs. (27.5±3.8) cm], respectively, with statistically significant differences observed in both groups (both P < 0.01). Conclusion:CEUS lymphography, as a preoperative planning strategy for LVA, can significantly increase the number and success rate of LVA anastomosis in patients with secondary upper limb lymphedema, shorten the duration of single anastomosis, and improve the short-term effect of limb volume reduction after LVA.

Objective:To study the differences of intestinal flora between neonatal rats with intrauterine hypoxia and healthy neonatal rats using high-throughput sequencing technology to determine the effects of intrauterine hypoxia on neonatal intestinal flora.Methods:Intrauterine hypoxia model were established in neonatal rats. On d1 and d7 after birth, intestinal samples were collected from intrauterine hypoxic group and normal control group and assigned into INH1 group (intrauterine hypoxia d1), INH7 group (intrauterine hypoxia d7), NOR1 group (normal control d1) and NOR7 group (normal control d7). 16S rRNA sequencing were conducted using these samples and the differences in the diversity, richness and composition of the flora among the groups were compared.Results:(1) The Alpha diversity of the intestinal flora in the INH1 group was higher than the NOR1 group. Specifically, both sobs and chao indices, representing the richness of the flora, in INH1 group were significantly higher than the NOR1 group (sobs index: 114.5±35.6 vs. 50.5±21.3, chao index: 135.6±38.5 vs. 73.9±28.8)( P<0.05). Compared with the NOR7 group, the mean values of sobs, ace, chao, simpson and shannon indices in the INH7 group showed no significant differences ( P>0.05). (2) At the phylum and genus level, the dominant bacterial groups in the intrauterine hypoxia group on d1 were firmicutes and streptococcus and proteus and escherichia for the normal control group. The difference of intestinal flora between intrauterine hypoxia group and the normal control group on d7 was smaller than the difference between the two groups on d1. Compared with INH1 group, the INH7 group had increased escherichia composition and decreased streptococcus composition. Conclusions:Intrauterine hypoxia changes the initial colonization and later affects the abundance and structural composition of the intestinal flora in newborn rats.

OBJECTIVE：To prepare chelerythrine nanoparticles（CHE-NPs），optimize their formulation ，and evaluate its drug release behavior in vitro and its inhibitory effect on melanoma. METHODS ：Using methoxy polyethylene glycol-poly （lactic-co- glycolic acid ）（mPEG-PLGA）as carrier ，CHE-NPs were prepared by the nano-precipitation method. HPLC method and dialysis bag method were used to determine entrapment efficiency and drug loading. The formulation of CHE-NPs was optimized by Box-Behnken response surface design using overall desirability （OD）of them as dependent variables ，CHE dosage ，mPEG-PLGA concentration and poloxamer 188（F68）concentration as independent variables. The particle size and Zeta potential of CHE-NPs prepared by the optimal formulation were detected ；the characteristics of drug release in vitro were investigated ；the effects of CHE and CHE-NPs on survival rate of mice B 16 melanoma cells were compared ，and median inhibition concentrations （IC50）of them were calculated. RESULTS ：The optimal formulation included CHE of 2 mg，mPEG-PLGA of 13 mg/mL，F68 of 1.8％. Average entrapment efficiency rate of CHE-NPs prepared by the optimal formulation was （80.18±1.11）％，average drug loading was （11.36±0.28）％，average OD value was 0.96±0.04 [the relative deviation from predicted value （0.90）of OD was 6.67％]； particle size was （113.1±1.40）nm，and Zeta potential was （－21.6±0.29）mV；polydispersity index was 0.07±0.01（n＝3）； accumulative release rates of CHE control and CHE-NPs were 90.87％ and 68.68％ within 8 h，and drug release behavior in vitro of the latter was in accordance with Weibull kinetic model. Inhibitory effect of CHE-NPs on B 16 melanoma cells was significantly stronger than that of CHE ；the 24 h IC 50 of CHE-NPs and CHEwere 69.35 and 107.36 μg/mL，respectively. CONCLUSIONS ：The prepared CHE-NPs show good sustained-effect and high capacity of drug loading ，and strengthen the inhibitory effect of CHE on melanoma.

Objective: To investigate nutritional quality of school lunch in some primary schools and middle schools in the Pearl River Delta, and to provide the scientific basis for improving the nutritional quality of students lunch and formulating scientific and effective interventions. Methods: Five-day lunch meal survey by chemical analysis were conducted, and students lunch at school were recorded by meal review in three age groups from 8 primary and middle schools in the Pear River Delat area. The energy and nutrient content were obtained and compared with the reference intake of dietary nutrients of student. Results: The average protein intake at lunch of all age groups had reached the recommended standard (80%-95%), the energy supply ratio of carbohydrate in the range of 38.3%-42.3%, the energy supply ratio of fat in 63% school meal exceeded the recommended standard. Vitamin A, vitamin B 1, vitamin B 2, calcium, iron and other nutrients were seriously inadequate; while sodium intake far exceeded the recommended standard. Conclusion The main nutrients of school lunch of primary and middle school in Pearl River Delta can basically meet the growth and development needs, but there are still some deficiency and unbalanced diet nutrient content which are lower than the recommended intake. It is recommended to strengthen nutrition education of catering enterprises and school to improve the scientific combination of diets.