Objective: To evaluates the association between maternal overweight/obesity during pregnancy and offspring risk of metabolic dysfunction associated steatotic liver disease (MASLD), providing theoretical evidence for early life MASLD prevention. Methods: An online search was conducted across ten databases (CNKI, Wanfang, SinoMed, PubMed, Embase, Web of Science, Cochrane Library, PROSPERO, PQDT Global, ScienceDirect) for research literature on the association between maternal overweight/obesity during pregnancy and the development of MASLD in offspring, with the search period spanning from January 2014 to December 2024. Two researchers independently screened literature, extracted data, and assessed study quality. Statistical analysis was performed using R 4.3.3. Results: Ten studies involving 10 229 participants were included, comprising 4 cohort studies and 6 case control studies. Cohort studies showed that maternal overweight and obesity significantly increased offspring MASLD risk ( RR=1.59, 95%CI=1.06-2.39, P <0.05), with moderate heterogeneity ( I 2=56.9%, P =0.07). Case control studies indicated a positive association between maternal overweight/obesity during pregnancy and offspring risk of MASLD( OR=2.00, 95%CI=1.68-2.39, P < 0.05), with low heterogeneity ( I 2=48.8%, P =0.08). Conclusions Maternal overweight/obesity during pregnancy positively correlates with offspring MASLD risk. Gestational weight management may reduce the risk.

Objective: To analyze the relationship between new surrogate marks of insulin resistance (IR) and bone mineral content (BMC) in adolescents, and predictive value of the new surrogate marks on low bone mass, so as to provide scientific basis for early identification and prevention of skeletal related diseases in adolescents. Methods: A total of 1 594 adolescents aged 12-18 years in Yinchuan City were selected by convenience sampling and stratified cluster random sampling from September 2017 to September 2020, and triglyceride and glucose index (TyG), triglyceride glucose-body mass index (TyG-BMI) and triglyceride/high density lipoprotein cholesterol (TG/HDL-C) were calculated as new simplified IR index. The correlation between different simplified IR indexes and BMC level was analyzed by partial correlation. Binary Logistic regression was used to analyze the relationship between IR index and low bone mass, and receiver operating characteristic (ROC) curve was constructed to analyze its evaluation effect on low bone mass. Results: After adjusting for confounding factors such as gender, age, smoking, drinking, family history of hypertension, systolic blood pressure (SBP) and diastolic blood pressure (DBP), the new surrogate marks of IR were positively correlated with BMC level (TyG: r =0.11, TyG-BMI: r =0.58, TG/HDL-C: r =0.21, P <0.01). After further adjustment of body mass index (BMI), fat mass (FM) and lean mass (LM), the relationship between IR indexes and BMC turned into negative correlation (TyG: r =-0.20, TyG-BMI: r =-0.18, TG/HDL-C: r=-0.14, P <0.01). After adjusting for confounding factors such as gender, age, smoking, drinking, family history of hypertension, SBP and DBP, Logistic regression results showed that the increase of TyG, TyG-BMI and TG/HDL-C levels reduced the possibility of low bone mass in adolescents (TyG: OR=0.63, 95%CI = 0.40-0.98, TyG-BMI: OR=0.94, 95%CI =0.93-0.96, TG/HDL-C: OR=0.31, 95%CI=0.17-0.58, P <0.01). After adjusting BMI, FM and LM, the above results were completely reversed. Girls with high TyG and TG/HDL-C levels were 4.95 and 4.38 times more likely to have low bone mass than those with low TyG and TG/HDL-C levels (TyG: OR=4.95, 95%CI =1.29- 18.95 , TG/HDL-C: OR=4.38, 95%CI=1.04-18.50, P <0.05). ROC curve showed that TyG-BMI had the best predictive value on low bone mass (AUC=0.80, 95% CI=0.77-0.83, P <0.01). Conclusion The new surrogate marks of IR in adolescents are negatively correlated with adolescent BMC, of which TyG-BMI is the best for assessing of low bone mass and can serving as a reliable indicator for early identification of low bone mass.

Hypoxia-inducible factor (HIF-1α), a core transcription factor responding to changes in cellular oxygen levels, is closely associated with a wide range of physiological and pathological conditions. However, its differential impacts on vascular cell types and molecular programs modulating human vascular homeostasis and regeneration remain largely elusive. Here, we applied CRISPR/Cas9-mediated gene editing of human embryonic stem cells and directed differentiation to generate HIF-1α-deficient human vascular cells including vascular endothelial cells, vascular smooth muscle cells, and mesenchymal stem cells (MSCs), as a platform for discovering cell type-specific hypoxia-induced response mechanisms. Through comparative molecular profiling across cell types under normoxic and hypoxic conditions, we provide insight into the indispensable role of HIF-1α in the promotion of ischemic vascular regeneration. We found human MSCs to be the vascular cell type most susceptible to HIF-1α deficiency, and that transcriptional inactivation of ANKZF1, an effector of HIF-1α, impaired pro-angiogenic processes. Altogether, our findings deepen the understanding of HIF-1α in human angiogenesis and support further explorations of novel therapeutic strategies of vascular regeneration against ischemic damage.
Humans ; Vascular Endothelial Growth Factor A/metabolism* ; Endothelial Cells/metabolism* ; Transcription Factors/metabolism* ; Gene Expression Regulation ; Hypoxia/metabolism* ; Cell Hypoxia/physiology*

Objective:To analyze the influence factors on the efficacy of immunosuppression therapy (IST) combined with eltrombopag and IST alone in the treatment of childhood severe aplastic anemia (SAA).Methods:A retrospective cohort study. A total of 124 children with SAA who were initially treated with IST at Beijing Children′s Hospital from March 2017 to May 2020 were enrolled. Clinical characteristics, laboratory examination and prognosis data were collected at the time of enrollment. According to the treatment plan, the children were divided into the eltrombopag combined with IST group (eltrombopag group) and the IST group. Binary Logistic regression model was used to analyze the factors affecting the efficacy of the two groups at 6 months of treatment, and the factors affecting the efficacy of the eltrombopag group at the end of follow-up.Results:There were 75 cases (45 males and 30 females) in the eltrombopag group. The age of diagnosis was 5.9 (3.5, 8.5) years. There were 49 patients in the IST group, including 23 males and 26 females, whose age at diagnosis was 6.2 (4.4, 8.8) years. The absolute lymphocyte count before treatment in the eltrombopag group was significantly lower than that in the IST group (1.1 (0.4, 1.6)×10 9vs. 2.1 (1.4, 2.8)×10 9/L). Absolute reticulocyte count in the eltrombopag group was significantly higher than that of IST group (26.9 (8.7, 54.2)×10 9vs. 9.5 (4.0, 19.0)×10 9/L) (both P<0.05). Influencing factors of 6-month response: a comparison between response and un-response groups in the eltrombopag treated patients showed that, before treatment, hemoglobin (69 (61, 78) vs. 64 (59, 68) g/L), platelet (10 (6, 16)×10 9vs. 6 (3, 8)×10 9/L), absolute reticulocyte count (ARC) (34.0 (15.8, 57.3)×10 9vs. 6.5 (4.6, 16.8)×10 9/L) and the response rate to granulocyte colony stimulating factor (G-CSF) after treatment (82.4% (47/57) vs. 9/18) were significantly different (all P<0.05). Logistic regression model analysis showed that ARC ( OR=1.09, 95% CI 1.02-1.18) and absolute neutrophil count were independent influencing factors of 6-month response rate in the eltrombopag group ( OR=0.00, 95% CI 0.00-0.89). ARC was also the independent influencing factors of the end of follow-up response rate in the eltrombopag group ( OR=1.04, 95% CI 1.01-1.07). Conclusions:Pre-treatment blood count and response to G-CSF were predictors of overall response to eltrombopag combined with IST. The higher the ARC before treatment, the higher the total response rate and complete response.

Spinocerebellar ataxia (SCA) is a group of progressively aggravated neurodegenerative disease with autosomal dominant inheritance. Cerebellar ataxia is the core symptom, which may be accompanied by pyramidal tract signs, extrapyramidal signs, cognitive dysfunction and peripheral neuropathy. Although SCA can be accurately diagnosed by genetic testing, treatment is still difficult. We review the pathogenesis and therapeutic targets of SCA in recent years, in terms of genetic or gene regulation abnormalities, disruption of protein quality control (PQC) network, disruption of energy homeostasis, stability maintenance of PQC system, maintenance of cerebellar Purkinje cell function, and regulation of neuroinflammation, so as to promote the transformation of preclinical research into human therapy.

Objective:To explore the prognostic value of peripheral blood lymphocyte subsets in lymphoma patients with different infection status of Epstein-Barr virus (EBV).Methods:A retrospective cohort study. A total of 333 lymphoma patients newly diagnosed from November 2012 to August 2023 in the Affiliated Hospital of Xuzhou Medical University were included in the study, including 185 patients with Diffuse Large B-cell Lymphoma (DLBCL), 100 patients with Natural Killer/T-cell Lymphoma (NKTCL), and 48 patients with Hodgkin Lymphoma (HL). Clinical data and laboratory indicators of patients were collected, including lymphocyte subset ratios detected by flow cytometry and EBV-DNA levels measured by real-time quantitative polymerase chain reaction. The survival status of patients was recorded through referring to medical records and telephone follow-up. The Kaplan-Meier method was used to plot survival curves and compare the survival rates among different groups. The Cox proportional hazards model was applied to analyze factors related to overall survival in lymphoma patients.Results:In the NKTCL group, 73.0% (73/100) were positive for EBV-DNA, which was higher than 43.8% (81/185) in the DLBCL group and 35.4% (17/48) in the HL group ( P<0.001). Kaplan-Meier survival curves showed that lower overall survival rates in the DLBCL group with abnormal levels of CD19 +B cells and CD16 +CD56 +NK cells (defined as either high or low referring to the reference intervals), with EBV-DNA negative and abnormal levels of CD19 +B cells, or with EBV-DNA positive and abnormal levels of CD16 +CD56 +NK cells, compared with the normal level group ( P<0.05). Multivariable analysis suggested that the abnormal level of CD19 +B cells was an independent adverse prognostic factor for DLBCL patients ( HR=2.098, 95% CI 1.181-3.727, P=0.011). EBV-DNA positivity ( HR=17.623, 95% CI 2.397-129.565, P=0.048) and Ann Arbor stage (Ⅲ/Ⅳ) ( HR=2.770, 95% CI 1.335-5.750, P=0.006) were adverse prognostic factors for NKTCL patients. Conclusion:There are differences in peripheral blood lymphocyte subsets among lymphoma patients with different EBV infection status, and CD19 +B cell levels may serve as an independent prognostic factor for DLBCL patients.

Objective:To investigate the clinical efficacy of modified Guipi Decoction combined with omeprazole in the treatment of acute non-variceal upper gastrointestinal bleeding (ANVUGIB) with failure of the spleen to control blood vessels syndrome.Methods:Prospective cohort study. A total of 120 patients from January 2018 to December 2021 Taihe County Hospital of Traditional Chinese Medicine with ANVUGIB of failure of the spleen to control blood vessels syndrome were selected, and the patients were divided into observation group and control group according to the random number table method, with 60 cases in each group. The control group was treated with a large dosage of proton pump inhibitor (omeprazole injection was injected intravenously first, and then omeprazole enteric coated tablets were taken); the observation group took Guipi Decoction on the basis of the control group, and both groups were treated for 7 days. TCM syndrome score, Hemoglobin (Hb) and hematocrit (HCT) levels were measured by colorimetry before and after the treatment. BUN was detected by urease glutamate dehydrogenase method. Prothrombin time (PT), activated partial thromboplastin time (APTT) and fibrinogen (FIB) levels were detected by immunoturbidimetry. The adverse reactions during treatment were recorded and the clinical efficacy was evaluated.Results:Two patients in the observation group and two patients in the control group dropped out of the study. After treatment, the scores of main symptoms, secondary symptoms and total scores in the observation group were lower than those in the control group ( t values were respectively 10.73, 4.45, 7.98, P<0.05). After treatment, the levels of HCT [(41.25 ± 5.03)% vs. (38.19 ± 5.26)%, t=2.95], Hb [(81.09 ± 5.23) g/L vs. (78.39 ± 5.37) g/L, t=2.74] in the observation group were higher than those in the control group ( P<0.01), and BUN [(4.38±0.96) mmol/L vs. (5.39 ± 1.13) mmol/L, t=5.19] was lower than that in the control group ( P<0.01); PT [(12.48 ± 0.67) s vs. (13.22 ± 0.73) s, t=5.69], APTT [(24.66 ± 2.29) s vs. (27.78 ± 2.04) s, t=7.75] were lower than those in the control group ( P<0.01), and FIB [(3.68 ± 0.62) g/L vs. (3.41 ± 0.74) g/L, t=2.13] level was higher than that in the control group ( P<0.05). The total effective rate of the observation group was 93.1% (54/58), and that of the control group was 79.3% (46/58), with statistical significance ( χ2=4.64, P=0.031). During the treatment, the incidence of adverse reactions in the control group was 3.4% (2/58), while that in the observation group was 1.7% (1/58), without statistical significance ( χ2=0.34, P=0.559). Conclusion:High-dosage omeprazole treatment with the addition of internal administration of Guipi Decoction can significantly improve coagulation function, correct the signs and symptoms associated with insufficient blood volume in the body circulation, improve hemostatic efficiency, and reduce the risk of bleeding in patients with ANVUGIB, without increasing the risk of patient safety with the drug.

OBJECTIVE: To investigate the effectiveness of finger reconstruction using nail flap anastomosing the nerve branch of the first toe nail bed. METHODS: Between January 2016 and December 2022, 18 patients (18 fingers) with thumb or finger nail bed defects were admitted. There were 12 males and 6 females, with an average age of 32 years (range, 19-42 years). Four cases were finger tip tissue damage caused by machine compression, and 4 cases were distal tissue necrosis after finger replantation. There were 9 cases of thumb injury, 3 cases of index finger injury, 5 cases of middle finger injury, and 1 case of ring finger injury. There were 11 cases of distal nail damage and 7 cases of distal nail root (including nail root) damage. The time from injury to admission was 1-5 hours, with an average of 2 hours. After debridement and anti-infection treatment for 5-7 days, the wounds in size of 1 cm×1 cm to 4 cm×3 cm were reconstructed by using nail flaps anastomosing the nerve branches of the first toe nail bed. The size of the nail flaps ranged from 1.5 cm×1.5 cm to 4.5 cm×3.5 cm. The donor sites were repaired with the flaps in 16 cases and skin graft in 2 cases. RESULTS: All nail flaps, flaps, and skin grafts survived after operation and the wounds healed by first intention. All patients were followed up 6-12 months (mean, 10 months). The nails of 18 cases were all grown, in which 16 cases had smooth nails with satisfactory appearances, 1 case had uneven nails, and 1 case had obvious scar hyperplasia around the suture opening. At 6 months after operation, the two-point discrimination of the skin flap was 4-8 mm (mean, 6 mm). Meanwhile, the skin grafts and flaps at the donor sites regained protective sensation, good abrasion resistance, and had no negative effect upon walking and wearing shoes. CONCLUSION The application of a nail flap that anastomoses the nerve branch of the first toe nail bed for finger reconstruction has minimal damage and can achieve good nail bed repair results.
Male ; Female ; Humans ; Adult ; Nails/injuries* ; Plastic Surgery Procedures ; Finger Injuries/surgery* ; Surgical Flaps/innervation* ; Skin Transplantation/methods* ; Toes/injuries* ; Soft Tissue Injuries/surgery* ; Treatment Outcome

Hair loss affects millions of people at some time in their life, and safe and efficient treatments for hair loss are a significant unmet medical need. We report that topical delivery of quercetin (Que) stimulates resting hair follicles to grow with rapid follicular keratinocyte proliferation and replenishes perifollicular microvasculature in mice. We construct dynamic single-cell transcriptome landscape over the course of hair regrowth and find that Que treatment stimulates the differentiation trajectory in the hair follicles and induces an angiogenic signature in dermal endothelial cells by activating HIF-1α in endothelial cells. Skin administration of a HIF-1α agonist partially recapitulates the pro-angiogenesis and hair-growing effects of Que. Together, these findings provide a molecular understanding for the efficacy of Que in hair regrowth, which underscores the translational potential of targeting the hair follicle niche as a strategy for regenerative medicine, and suggest a route of pharmacological intervention that may promote hair regrowth.
Mice ; Animals ; Quercetin/pharmacology* ; Endothelial Cells ; Hair ; Hair Follicle ; Alopecia

Gallic Acid/pharmacology* ; Humans ; Senotherapeutics ; Stem Cells