BACKGROUND:Parkinson's disease is a multifactorial neurological disorder characterized by progressive loss of dopaminergic neurons,and dimethyl fumarate(DMF)has potent neuroprotective and immunomodulatory effects in neurodegenerative diseases. OBJECTIVE:To explore the neuroprotective mechanism of DMF in a mouse model of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP)-induced Parkinson's disease. METHODS:Twenty-four C57BL/6 mice were selected and randomly divided into control group,model group,low-dose DMF,and high-dose DMF groups.An animal model of Parkinson's disease was established in the latter three groups by intraperitoneal injection of 30 mg/kg MPTP,once a day for 5 consecutive days.Intragastric administration was given 30 minutes after each injection of MPTP.Mice in the low-dose DMF group(30 mg/kg)and high-dose DMF group(50 mg/kg)were intragastrically administered once a day for 7 consecutive days.The control and model groups were initially administered the same dose of normal saline.Behavioral testing,western blot,oxidative stress marker detection,and immunohistochemical staining were used to analyze the regulatory effects of DMF on oxidative stress and Keap1/Nrf2 signaling pathway in MPTP-induced Parkinson's disease mice,as well as the protective mechanism of DMF on degeneration of dopamine neurons. RESULTS AND CONCLUSION:Compared with the model group,mice in the low-dose DMF group exhibited significant improvements in motor retardation and postural imbalance(P<0.01),with even more remarkable improvements observed in the high-dose DMF group(P<0.01).Compared with the control group,the model group showed a significant increase in the oxidative stress marker malondialdehyde and a decrease in superoxide dismutase expression(P<0.01).Compared with the model group,the low-dose DMF group reduced malondialdehyde production and increased superoxide dismutase expression(P<0.01),and similar improvements were observed in the high-dose DMF group(P<0.01).Immunohistochemical and western blot assays demonstrated a significant decrease in the number of dopaminergic neurons and tyrosine hydroxylase protein expression in the substantia nigra of mice in the model group compared with the control group(P<0.01).However,in the low-dose DMF group,there was an increase in the number of dopaminergic neurons and tyrosine hydroxylase protein expression in the substantia nigra(P<0.01),with even more significant improvements in the high-dose DMF group(P<0.01).Western blot results revealed that the model group exhibited elevated Keap1 protein expression and decreased Nrf2 protein expression.In contrast,the DMF groups showed reduced Keap1 protein expression and increased Nrf2 protein expression compared to the model group(P<0.01).To conclude,DMF regulates the Keap1/Nrf2 pathway in the substantia nigra of mice with Parkinson's disease,and this regulatory effect is positively correlated with the dose of DMF(P<0.01).Therefore,we infer that DMF exerts neuroprotective effects through the Keap1/Nrf2 signaling pathway.

Objective:To investigate the status and influencing factors of substantial weight retention in patients with gestational diabetes mellitus (GDM) in early postpartum.Methods:This cross-sectional study employed a convenience sampling method to select 373 patients with GDM who underwent a 6-week postpartum health check at the Postpartum Health Clinic of Women′s Hospital of Nanjing Medical University from February to July in 2023. According to postpartum weight retention (PPWR) on the survey day, the participants were divided into a substantial PPWR group (≥5 kg, 139 cases) and a non-substantial PPWR group (<5 kg, 234 cases). Independent sample t-tests and χ2 tests were used to compare differences in demographic data, clinical data, and biochemical indicators between the two groups. Binary logistic regression was used to analyze the influencing factors of early substantial postpartum weight retention in patients with GDM. Results:A total of 37.27% (139/373) of GDM patients experienced substantial postpartum weight retention at 6 weeks postpartum. The rates of diabetes in family history, excessive gestational weight gain, gestational hypertension, and infant neonatal intensive care unit (NICU) admission in substantial PPWR group were all significantly higher than those in the non-substantial PPWR group (32.37% vs 23.08%, 73.38% vs 20.09%, 13.67% vs 5.56%, 21.58% vs 9.83%) (all P<0.05); but the proportion of overweight or obese before pregnancy and postpartum self-monitoring of blood glucose were both lower in the substantial PPWR group than those in the non-substantial PPWR group (25.18% vs 41.03%, 17.99% vs 27.78%)(all P<0.05). Binary logistic regression indicated that family history of diabetes ( OR=2.826, 95% CI: 1.517-5.265), excessive gestational weight gain ( OR=19.240, 95% CI: 10.360-35.732), and infant NICU admission ( OR=2.447, 95% CI: 1.150-5.205) were positively related to the occurrence of substantial weight retention in patients with GDM in early postpartum, whereas pre-pregnancy overweight or obesity ( OR=0.189, 95% CI: 0.100-0.360) was negatively correlated to substantial weight retention in patients with GDM in early postpartum (all P<0.05). Conclusion:Substantial weight retention is prevalent among GDM patients in early postpartum, which is significantly influenced by family history of diabetes, pre-pregnancy overweight or obesity, excessive gestational weight gain, and infant NICU admission history.

Dental-derived mesenchymal stem cells (DMSC), owing to their self-renewal capacity and multi-lineage differentiation potential, have demonstrated significant promise in the field of oral tissue regeneration. Mitochondria, as essential organelles within cells, can not only be responsible for energy metabolism but also influence the maintenance of stem cell stemness and the direction of differentiation by regulating cellular metabolic processes, apoptosis, and signal transduction pathways. In recent years, the mechanisms by which mitochondria participating in the osteogenic and odontogenic differentiation of DMSC have gradually become a research focus. This paper reviews the regulatory mechanisms of mitochondria in the osteogenic and odontogenic differentiation of DMSC, with emphasis on how mitochondrial energy metabolism (oxidative phosphorylation and glycolysis) and quality control processes (namely biogenesis, dynamics as fission and fusion, and autophagy) modulate the differentiation of DMSC. The aim is to provide a theoretical basis and reference for the research and application of dental pulp regeneration, periodontal tissue regeneration, and other aspects of oral tissue engineering.

Dental-derived mesenchymal stem cells (DMSC), owing to their self-renewal capacity and multi-lineage differentiation potential, have demonstrated significant promise in the field of oral tissue regeneration. Mitochondria, as essential organelles within cells, can not only be responsible for energy metabolism but also influence the maintenance of stem cell stemness and the direction of differentiation by regulating cellular metabolic processes, apoptosis, and signal transduction pathways. In recent years, the mechanisms by which mitochondria participating in the osteogenic and odontogenic differentiation of DMSC have gradually become a research focus. This paper reviews the regulatory mechanisms of mitochondria in the osteogenic and odontogenic differentiation of DMSC, with emphasis on how mitochondrial energy metabolism (oxidative phosphorylation and glycolysis) and quality control processes (namely biogenesis, dynamics as fission and fusion, and autophagy) modulate the differentiation of DMSC. The aim is to provide a theoretical basis and reference for the research and application of dental pulp regeneration, periodontal tissue regeneration, and other aspects of oral tissue engineering.

Objective To profile ubiquitination in cysteinyl aspartate-specific proteinase-2(CASP2)deficient cells under heat shock and investigate the role of CASP2 in stress response.Methods Ubiquitination levels in subcellular fractions of control and C ASP2 knockout(KO)cells were detected via Western blotting.After 2 hours of heat shock treatment,Soluble Ⅱ and Pellet fractions were collected from both control and CASP2 KO cells for ubiquitinome analysis.Anti-di-glycine remnant(K-ε-GG)antibody-based proteomic analysis was performed to identify differentially ubiquitinated proteins and associated key signaling pathways.Proteins that displayed significantly upregulated ubiquitination in CASP2 KO cells under heat shock were subjected to His-tag pull-down assays to find out whether CASP2 regulated the ubiquitination of these proteins.Results Under heat shock,CASP2 KO cells displayed significantly higher accumulation of overloaded ubiquitinated conjugates in the Pellet fraction compared to controls.Ubiquitinomics analysis revealed substantial alterations in protein ubiquitination patterns following CASP2 KO.One hundred proteins exhibited significantly elevated ubiquitination levels while 36 proteins had their ubiquitination reduced relative to controls.Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis indicated that hyper-ubiquitinated proteins were primarily associated with Huntington disease,Alzheimer disease,bile secretion,carbon metabolism and autophagy.His-tag pull-down assays combined with Western blotting revealed increased ubiquitination of nicotinamide adenine dinucleotide reduced-ubiquinone oxidoreductase 1 beta subcomplex subunit 3(NDUFB3)and autophagy-related protein 9A(ATG9A)in CASP2 KO cells under heat shock.Conclusion Overloaded ubiquitinated conjugates are accumulated due to CASP2 deficiency during heat shock.CASP2 modulates ubiquitination levels through multiple signaling pathways.

This study was aimed at preliminarily assessing the prevalence of latent tuberculosis infection(LTBI)among cattle farming and slaughterhouse workers across Wuxue,Xianning,and Yichang Cities in Hubei Province,and exploring associated risk factors.Data on cattle farming and slaughterhouse workers were gathered via a questionnaire.LTBI detection was performed with a tu-berculin skin test and interferon-gamma release assay,and influencing factors were subsequently analyzed.The LTBI prevalence among cattle farming and slaughterhouse personnel in the three cities was 30.50%,and a higher rate was observed in slaughterhouse workers(39.01%)than cattle farmers(21.63%)(P<0.01).Multifactor analysis indicated that working in slaughterhouses(95%CI:1.582-3.878),having a history of tuberculosis(95%CI:1.377-25.057)or BCG vaccination(95%CI:1.229-3.285),and having a college education or above(95%CI:0.303-0.859)were significant factors influencing LTBI positivity in these personnel.Having more than 30 years of work experience(95%CI:1.303-18.782)was a risk factor for personnel at cattle breeding farms.Among slaugh-terhouse personnel,having a college education or above(95%CI:0.164-0.894),11-20 years of work experience(95%CI:0.122-0.994),or a history of tuberculosis(95%CI:1.661-64.397);performing logistics work(95%CI:3.234-126.424);and working in slaughter-related positions(95%CI:1.209-19.639)were associated with LTBI positivity.Therefore,the slaughterhouse workers in the three cities had higher LTBI rates than the cattle farming workers,thus underscoring the need for increased attention to personnel in logistics and slaughter-related positions.

This study was aimed at preliminarily assessing the prevalence of latent tuberculosis infection(LTBI)among cattle farming and slaughterhouse workers across Wuxue,Xianning,and Yichang Cities in Hubei Province,and exploring associated risk factors.Data on cattle farming and slaughterhouse workers were gathered via a questionnaire.LTBI detection was performed with a tu-berculin skin test and interferon-gamma release assay,and influencing factors were subsequently analyzed.The LTBI prevalence among cattle farming and slaughterhouse personnel in the three cities was 30.50%,and a higher rate was observed in slaughterhouse workers(39.01%)than cattle farmers(21.63%)(P<0.01).Multifactor analysis indicated that working in slaughterhouses(95%CI:1.582-3.878),having a history of tuberculosis(95%CI:1.377-25.057)or BCG vaccination(95%CI:1.229-3.285),and having a college education or above(95%CI:0.303-0.859)were significant factors influencing LTBI positivity in these personnel.Having more than 30 years of work experience(95%CI:1.303-18.782)was a risk factor for personnel at cattle breeding farms.Among slaugh-terhouse personnel,having a college education or above(95%CI:0.164-0.894),11-20 years of work experience(95%CI:0.122-0.994),or a history of tuberculosis(95%CI:1.661-64.397);performing logistics work(95%CI:3.234-126.424);and working in slaughter-related positions(95%CI:1.209-19.639)were associated with LTBI positivity.Therefore,the slaughterhouse workers in the three cities had higher LTBI rates than the cattle farming workers,thus underscoring the need for increased attention to personnel in logistics and slaughter-related positions.

Objective:To investigate the status and influencing factors of substantial weight retention in patients with gestational diabetes mellitus (GDM) in early postpartum.Methods:This cross-sectional study employed a convenience sampling method to select 373 patients with GDM who underwent a 6-week postpartum health check at the Postpartum Health Clinic of Women′s Hospital of Nanjing Medical University from February to July in 2023. According to postpartum weight retention (PPWR) on the survey day, the participants were divided into a substantial PPWR group (≥5 kg, 139 cases) and a non-substantial PPWR group (<5 kg, 234 cases). Independent sample t-tests and χ2 tests were used to compare differences in demographic data, clinical data, and biochemical indicators between the two groups. Binary logistic regression was used to analyze the influencing factors of early substantial postpartum weight retention in patients with GDM. Results:A total of 37.27% (139/373) of GDM patients experienced substantial postpartum weight retention at 6 weeks postpartum. The rates of diabetes in family history, excessive gestational weight gain, gestational hypertension, and infant neonatal intensive care unit (NICU) admission in substantial PPWR group were all significantly higher than those in the non-substantial PPWR group (32.37% vs 23.08%, 73.38% vs 20.09%, 13.67% vs 5.56%, 21.58% vs 9.83%) (all P<0.05); but the proportion of overweight or obese before pregnancy and postpartum self-monitoring of blood glucose were both lower in the substantial PPWR group than those in the non-substantial PPWR group (25.18% vs 41.03%, 17.99% vs 27.78%)(all P<0.05). Binary logistic regression indicated that family history of diabetes ( OR=2.826, 95% CI: 1.517-5.265), excessive gestational weight gain ( OR=19.240, 95% CI: 10.360-35.732), and infant NICU admission ( OR=2.447, 95% CI: 1.150-5.205) were positively related to the occurrence of substantial weight retention in patients with GDM in early postpartum, whereas pre-pregnancy overweight or obesity ( OR=0.189, 95% CI: 0.100-0.360) was negatively correlated to substantial weight retention in patients with GDM in early postpartum (all P<0.05). Conclusion:Substantial weight retention is prevalent among GDM patients in early postpartum, which is significantly influenced by family history of diabetes, pre-pregnancy overweight or obesity, excessive gestational weight gain, and infant NICU admission history.

Objective:To retrospectively analyze the treatment status of tyrosine kinase inhibitors (TKI) in newly diagnosed patients with chronic myeloid leukemia (CML) in China.Methods:Data of chronic phase (CP) and accelerated phase (AP) CML patients diagnosed from January 2006 to December 2022 from 77 centers, ≥18 years old, and receiving initial imatinib, nilotinib, dasatinib or flumatinib-therapy within 6 months after diagnosis in China with complete data were retrospectively interrogated. The choice of initial TKI, current TKI medications, treatment switch and reasons, treatment responses and outcomes as well as the variables associated with them were analyzed.Results:6 893 patients in CP ( n=6 453, 93.6%) or AP ( n=440, 6.4%) receiving initial imatinib ( n=4 906, 71.2%), nilotinib ( n=1 157, 16.8%), dasatinib ( n=298, 4.3%) or flumatinib ( n=532, 7.2%) -therapy. With the median follow-up of 43 ( IQR 22-75) months, 1 581 (22.9%) patients switched TKI due to resistance ( n=1 055, 15.3%), intolerance ( n=248, 3.6%), pursuit of better efficacy ( n=168, 2.4%), economic or other reasons ( n=110, 1.6%). The frequency of switching TKI in AP patients was significantly-higher than that in CP patients (44.1% vs 21.5%, P<0.001), and more AP patients switched TKI due to resistance than CP patients (75.3% vs 66.1%, P=0.011). Multi-variable analyses showed that male, lower HGB concentration and ELTS intermediate/high-risk cohort were associated with lower cytogenetic and molecular responses rate and poor outcomes in CP patients; higher WBC count and initial the second-generation TKI treatment, the higher response rates; Ph + ACA at diagnosis, poor PFS. However, Sokal intermediate/high-risk cohort was only significantly-associated with lower CCyR and MMR rates and the poor PFS. Lower HGB concentration and larger spleen size were significantly-associated with the lower cytogenetic and molecular response rates in AP patients; initial the second-generation TKI treatment, the higher treatment response rates; lower PLT count, higher blasts and Ph + ACA, poorer TFS; Ph + ACA, poorer OS. Conclusion:At present, the vast majority of newly-diagnosed CML-CP or AP patients could benefit from TKI treatment in the long term with the good treatment responses and survival outcomes.

Objective:The preliminary results was reported regarding the treatment of mesenteric torsion by mesenteric fixation in the last decade, especially preventing recurrence of mesenteric torsion by mesenteric fan-shaped fixation.Methods:We selected 12 patients who received emergency operation in Chongqing Hospital of the First Affiliated Hospital of Guangzhou University of Chinese Medicine from December 2010 to March 2022. All of them were made a definite diagnose of mesenteric torsion by the preoperative CT scan or exploratory laparotomy. The recurrence of mesenteric torsion will be prevented by taking the operation of mesenteric fan-shaped fixation. This technique is suitable for the patient who is suffering total mesenteric torsion, but enteric necrosis is excluded affirmatively. The operation is consists of the following progress: (1) Exploratory laparotomy to check for necrosis of the bowel and for lesions other than torsion. (2) Mesenteric torsion derotation.(3) Mesenteric linear fixation; the right posterior lower border of the small mesentery (terminal ileal mesentery) is intermittently sutured to the posterior peritoneum of the right lower quadrant to increase the width of the base of the small mesentery. (4) Mesenteric fan-shaped fixation, which is fan-shaped to the lower left and fixed in the posterior peritoneum, shortening the length of the mesentery and further increasing the width of the mesentery and posterior peritoneal fixation.Results:A total of 12 patients with mesenteric torsion were treated by operation for 15 times in all. Among them, 3 cases received resection of most small bowel were performed without recurrence; 3 patients received only derotation for a total of 4 times, 2 cases recurred, 1 of them recurred twice; 4 cases underwent derotation and mesenteric linear fixation,and 1 case recurred. Four patients with derotation and mesenteric fan-shaped fixation recovered well without recurrence.Conclusion:Mesenteric fan-shaped fixation may be an effective operative type to reduce or avoid postoperative recurrence of mesenteric torsion.