ObjectiveTo investigate the mechanism by which Xianglian Huazhuo prescription （XLHZ） ameliorates chronic atrophic gastritis （CAG） through regulating glycolysis via the microRNA-34b-5p （miR-34b-5p）/6-phosphofructo-2-kinase/fructose-2，6-bisphosphatase 1 （PFKFB1） signaling pathway. MethodsBioinformatic screening was performed to identify the target genes of miR-34b-5p. In the animal experiments， a mouse model of CAG was established through a combination of N-methyl-N′-nitro-N-nitrosoguanidine （MNNG）， ranitidine， and irregular feeding. The mice were randomized into the following groups： normal， model， Morodan group （2 g·kg^-1）， and high-， medium-， and low-dose XLHZ groups（7.2，3.8，1.9 g·kg^-1）. In the cell experiments， GES-1 cells were treated with MNNG for the modeling of CAG and grouped as follows： GES-1， MNNG+GES-1， MNNG+GES-1+XLHZ（10%）， MNNG+GES-1+miR-34b-5p mimics， MNNG+GES-1+miR-34b-5p inhibitor， MNNG+GES-1+PFKFB1 inhibitor， and MNNG+GES-1+PFKFB1 mimics+XLHZ（10%）. The general conditions of mice were observed. Real-time PCR was adopted to measure the expression levels of miRNA-34b-5p and PFKFB1 mRNA in the gastric mucosa of mice in each group. Dual luciferase reporter gene was used to verify the targeting interaction between miR-34b-5p and PFKFB1 in GES-1 cells exposed to MNNG. The cell-counting kit-8 （CCK-8） was used to screen the drug-containing serum concentration. Real-time PCR was employed to verify the transfection efficiency. Fluorescent probes were used to detect the expression and nuclear translocation of hypoxia-inducible factor-1α （HIF-1α） in each group of cells. The protein levels of HIF-1α， hexokinase 2 （HK2）， PFKFB1， phosphofructokinase 1 （PFK1）， and lactate dehydrogenase （LDHA） in the gastric mucosa of mice were determined by Western blot. The levels of glucose consumption and lactate in the serum and cells were measured by biochemical methods. Enzyme-linked immunosorbent assay （ELISA） was adopted to measure the content of adenosine triphosphate （ATP） in the gastric mucosa tissue and cells. ResultsThe animal experiments showed that compared with the normal group， the model group exhibited symptoms including mental fatigue， lethargy， sparse and dull fur， a tendency to curl up， sluggish responses， reduced food and water intake， and slow body weight gain. In addition， the model group showed decreased expression of miRNA-34b-5p （P<0.01）， increased mRNA level of PFKFB1 （P<0.01）， upregulated protein levels of HIF-1α， HK2， PFKFB1， PFK1， and LDHA （P<0.01）， and increased glucose consumption， lactate content， and ATP content （P<0.01）. Compared with the model group， the XLHZ group and Morodan group showed improved mental state， gradually improved fur， increased activity， food and water intake， and body weight. HE showed that each treatment group exhibited well arranged and increased gastric mucosal glands， reduced inflammatory cells， and recovered gastric pits. Transmission electron microscopy showed that the size of mitochondria in each treatment group returned to normal， with no obvious irregular shape， complete and clear cristae， and uniform matrix. Furthermore， each treatment group showed increased expression of miRNA-34b-5p （P<0.05）， reduced mRNA level of PFKFB1 （P<0.05）， downregulated protein levels of HIF-1α， HK2， PFKFB1， PFK1， and LDHA （P<0.05）， and decreased glucose consumption， lactic acid， and ATP （P<0.05）. The cell experiments showed that the expression and nuclear translocation of HIF-1α were reduced in all groups after treatment （P<0.05）. The cell transfection efficiency was satisfactory （P<0.05）. miR-34b-5p exhibited an effect comparable to that of XLHZ， effectively inhibiting glycolysis， whereas PFKFB1 promoted glycolysis and reversed the protective effect of XLHZ in CAG mice （P<0.05）. ConclusionXLHZ could regulate the miR-34b-5p/PFKFB1 axis to inhibit glycolysis， thereby ameliorating MNNG-induced gastric mucosal atrophy.

ObjectiveTo investigate the mechanism by which Xianglian Huazhuo prescription （XLHZ） ameliorates chronic atrophic gastritis （CAG） through regulating glycolysis via the microRNA-34b-5p （miR-34b-5p）/6-phosphofructo-2-kinase/fructose-2，6-bisphosphatase 1 （PFKFB1） signaling pathway. MethodsBioinformatic screening was performed to identify the target genes of miR-34b-5p. In the animal experiments， a mouse model of CAG was established through a combination of N-methyl-N′-nitro-N-nitrosoguanidine （MNNG）， ranitidine， and irregular feeding. The mice were randomized into the following groups： normal， model， Morodan group （2 g·kg^-1）， and high-， medium-， and low-dose XLHZ groups（7.2，3.8，1.9 g·kg^-1）. In the cell experiments， GES-1 cells were treated with MNNG for the modeling of CAG and grouped as follows： GES-1， MNNG+GES-1， MNNG+GES-1+XLHZ（10%）， MNNG+GES-1+miR-34b-5p mimics， MNNG+GES-1+miR-34b-5p inhibitor， MNNG+GES-1+PFKFB1 inhibitor， and MNNG+GES-1+PFKFB1 mimics+XLHZ（10%）. The general conditions of mice were observed. Real-time PCR was adopted to measure the expression levels of miRNA-34b-5p and PFKFB1 mRNA in the gastric mucosa of mice in each group. Dual luciferase reporter gene was used to verify the targeting interaction between miR-34b-5p and PFKFB1 in GES-1 cells exposed to MNNG. The cell-counting kit-8 （CCK-8） was used to screen the drug-containing serum concentration. Real-time PCR was employed to verify the transfection efficiency. Fluorescent probes were used to detect the expression and nuclear translocation of hypoxia-inducible factor-1α （HIF-1α） in each group of cells. The protein levels of HIF-1α， hexokinase 2 （HK2）， PFKFB1， phosphofructokinase 1 （PFK1）， and lactate dehydrogenase （LDHA） in the gastric mucosa of mice were determined by Western blot. The levels of glucose consumption and lactate in the serum and cells were measured by biochemical methods. Enzyme-linked immunosorbent assay （ELISA） was adopted to measure the content of adenosine triphosphate （ATP） in the gastric mucosa tissue and cells. ResultsThe animal experiments showed that compared with the normal group， the model group exhibited symptoms including mental fatigue， lethargy， sparse and dull fur， a tendency to curl up， sluggish responses， reduced food and water intake， and slow body weight gain. In addition， the model group showed decreased expression of miRNA-34b-5p （P<0.01）， increased mRNA level of PFKFB1 （P<0.01）， upregulated protein levels of HIF-1α， HK2， PFKFB1， PFK1， and LDHA （P<0.01）， and increased glucose consumption， lactate content， and ATP content （P<0.01）. Compared with the model group， the XLHZ group and Morodan group showed improved mental state， gradually improved fur， increased activity， food and water intake， and body weight. HE showed that each treatment group exhibited well arranged and increased gastric mucosal glands， reduced inflammatory cells， and recovered gastric pits. Transmission electron microscopy showed that the size of mitochondria in each treatment group returned to normal， with no obvious irregular shape， complete and clear cristae， and uniform matrix. Furthermore， each treatment group showed increased expression of miRNA-34b-5p （P<0.05）， reduced mRNA level of PFKFB1 （P<0.05）， downregulated protein levels of HIF-1α， HK2， PFKFB1， PFK1， and LDHA （P<0.05）， and decreased glucose consumption， lactic acid， and ATP （P<0.05）. The cell experiments showed that the expression and nuclear translocation of HIF-1α were reduced in all groups after treatment （P<0.05）. The cell transfection efficiency was satisfactory （P<0.05）. miR-34b-5p exhibited an effect comparable to that of XLHZ， effectively inhibiting glycolysis， whereas PFKFB1 promoted glycolysis and reversed the protective effect of XLHZ in CAG mice （P<0.05）. ConclusionXLHZ could regulate the miR-34b-5p/PFKFB1 axis to inhibit glycolysis， thereby ameliorating MNNG-induced gastric mucosal atrophy.

Objective:To investigate the efficacy of two types of micro-focused ultrasound devices combined with botulinum toxin type A (BoNT-A) injection for facial rejuvenation.Methods:A retrospective study was conducted, including 60 female patients aged 28-70 (41.3±7.9) years, who received facial rejuvenation treatment at the Department of Plastic and Reconstructive Surgery, Zhongnan Hospital of Wuhan University, from April 2023 to April 2024. Patients were divided into two groups based on the treatment method: the control group (received only micro-focused ultrasound treatment, n=30) and the combined group (received both micro-focused ultrasound and BoNT-A injection, n=30). Additionally, patients were further categorized into four subgroups based on the type of micro-focused ultrasound device used: Peninsula Microultra? (PM) device group ( n=15), Intelligent Ultrasound? (IU) device group ( n=15), PM device + BoNT-A injection group ( n=15), and IU device + BoNT-A injection group ( n=15). The severity of facial wrinkles was assessed using the wrinkle severity rating scale (WSRS), the Merz aesthetic scale (MAS), and the global aesthetic improvement scale (GAIS) at baseline and 6 months post-treatment. Adverse event rates were also recorded. Results:At 6 months post-treatment, the combined group showed significantly lower WSRS and MAS scores than the control group (both P<0.001). No significant differences were found between the PM and IU device groups, or between the PM + BoNT-A and IU + BoNT-A groups regarding WSRS and MAS scores (all P>0.05). Self-reported GAIS improvement was 56.7% (17/30) for the control group and 80.0% (24/30) for the combined group, with the combined group showing superior results ( P=0.015). The physician-assessed GAIS improvement was 70.0% (21/30) for the control group and 96.7% (29/30) for the combined group, again with the combined group showing superior results ( P=0.007). No significant differences were found in self-reported or physician-assessed GAIS improvement between the PM and IU device groups, or between the PM + BoNT-A and IU + BoNT-A groups (all P>0.05). No severe adverse reactions, such as blisters, scabbing, purpura, bruising, scarring, peripheral facial paralysis, allergies, muscle weakness, dysphagia, or dysphonia, were observed in any patient. Conclusion:The combination of micro-focused ultrasound and BoNT-A injection for facial rejuvenation is more effective than micro-focused ultrasound alone, while there are no significant differences in efficacy between the two micro-focused ultrasound devices.

OBJECTIVE: This study aimed to explore the association between body mass index (BMI) and mortality based on the 10-year population-based multicenter prospective study. METHODS: A general population-based multicenter prospective study was conducted at four sites in rural China between 2013 and 2023. Multivariate Cox proportional hazards models and restricted cubic spline analyses were used to assess the association between BMI and mortality. Stratified analyses were performed based on the individual characteristics of the participants. RESULTS: Overall, 19,107 participants with a sum of 163,095 person-years were included and 1,910 participants died. The underweight (< 18.5 kg/m ²) presented an increase in all-cause mortality (adjusted hazards ratio [ aHR] = 2.00, 95% confidence interval [ CI]: 1.66-2.41), while overweight (≥ 24.0 to < 28.0 kg/m ²) and obesity (≥ 28.0 kg/m ²) presented a decrease with an aHR of 0.61 (95% CI: 0.52-0.73) and 0.51 (95% CI: 0.37-0.70), respectively. Overweight ( aHR = 0.76, 95% CI: 0.67-0.86) and mild obesity ( aHR = 0.72, 95% CI: 0.59-0.87) had a positive impact on mortality in people older than 60 years. All-cause mortality decreased rapidly until reaching a BMI of 25.7 kg/m ² ( aHR = 0.95, 95% CI: 0.92-0.98) and increased slightly above that value, indicating a U-shaped association. The beneficial impact of being overweight on mortality was robust in most subgroups and sensitivity analyses. CONCLUSION This study provides additional evidence that overweight and mild obesity may be inversely related to the risk of death in individuals older than 60 years. Therefore, it is essential to consider age differences when formulating health and weight management strategies.
Humans ; Body Mass Index ; China/epidemiology* ; Male ; Female ; Middle Aged ; Prospective Studies ; Rural Population/statistics & numerical data* ; Aged ; Follow-Up Studies ; Adult ; Mortality ; Cause of Death ; Obesity/mortality* ; Overweight/mortality*

Skin wound repair is critically regulated by peripheral nerves. Injury or dysfunction of these nerves represents a key factor impairing the healing of pathological wounds, such as diabetic ulcers and deep burns. The mechanisms by which peripheral nerves participate in cutaneous wound healing primarily involve modulation of immune responses, construction of stem cell niches, and promotion of angiogenesis. Sensory neurons initiate and mediate essential local immune responses, contribute to the epidermal stem cell microenvironment, and support regenerative potential. Sympathetic nerves bidirectionally regulate immune homeostasis via the release of various neuromodulators and precisely control the activation of hair follicle stem cells as well as the homeostasis of melanocyte stem cells. Schwann cells also play pivotal roles in immune modulation, balancing repair processes and mitigating scar formation. During revascularization, sensory and autonomic nerve terminals release neurotransmitters that precisely regulate vasomotor activity and angiogenesis, while Schwann cells facilitate the reconstruction of functional vascular networks via potent paracrine signaling. This review systematically summarizes the crucial roles of peripheral nerves in skin wound repair, with emphasis on their regulatory mechanisms in immune responses, stem cell activation and homeostasis, and vascular dynamics, thereby providing insights into the development of novel therapeutic strategies targeting peripheral nerve regulation.
Humans ; Wound Healing/physiology* ; Peripheral Nerves/physiology* ; Schwann Cells/physiology* ; Skin/injuries* ; Animals

Idiopathic pulmonary fibrosis (IPF), a chronic interstitial lung disease, is characterized by aberrant wound healing, excessive scarring and the formation of myofibroblastic foci. Although the role of alternative splicing (AS) in the pathogenesis of organ fibrosis has garnered increasing attention, its specific contribution to pulmonary fibrosis remains incompletely understood. In this study, we identified an up-regulation of serine/arginine-rich splicing factor 7 (SRSF7) in lung fibroblasts derived from IPF patients and a bleomycin (BLM)-induced mouse model, and further characterized its functional role in both human fetal lung fibroblasts and mice. We demonstrated that enhanced expression of Srsf7 in mice spontaneously induced alveolar collagen accumulation. Mechanistically, we investigated alternative splicing events and revealed that SRSF7 modulates the alternative splicing of pyruvate kinase (PKM), leading to metabolic dysregulation and fibroblast activation. In vivo studies showed that fibroblast-specific knockout of Srsf7 in conditional knockout mice conferred resistance to bleomycin-induced pulmonary fibrosis. Importantly, through drug screening, we identified lomitapide as a novel modulator of SRSF7, which effectively mitigated experimental pulmonary fibrosis. Collectively, our findings elucidate a molecular pathway by which SRSF7 drives fibroblast metabolic dysregulation and propose a potential therapeutic strategy for pulmonary fibrosis.

OBJECTIVE: To compare the efficacy and safety of intravenous colistin sulfate combined with nebulized inhalation versus intravenous monotherapy for pulmonary infections caused by carbapenem-resistant organism (CRO). METHODS: A multicenter retrospective cohort study was conducted. Clinical data were collected from patients admitted to the intensive care unit (ICU) of 10 tertiary class-A hospitals in Henan Province between July 2021 and May 2023, who received colistin sulfate for CRO pulmonary infections. Data included baseline characteristics, inflammatory markers [white blood cell count (WBC), neutrophil count (NEU), procalcitonin (PCT), C-reactive protein (CRP)], renal function indicators [serum creatinine (SCr), blood urea nitrogen (BUN)], life support measures, anti-infection regimens, clinical efficacy, microbiological clearance rate, and prognostic outcomes. Patients were divided into two groups: intravenous group (colistin sulfate monotherapy via intravenous infusion) and combination group ((intravenous infusion combined with nebulized inhalation of colistin sulfate). Changes in parameters before and after treatment were analyzed. RESULTS: A total of 137 patients with CRO pulmonary infections were enrolled, including 89 in the intravenous group and 48 in the combination group. Baseline characteristics, life support measures, daily colistin dose, and combination regimens (most commonly colistin sulfate plus carbapenems in both groups) showed no significant differences between two groups. The combination group exhibited higher clinical efficacy [77.1% (37/48) vs. 59.6% (52/89)] and microbiological clearance rate [60.4% (29/48) vs. 39.3% (35/89)], both P < 0.05. Pre-treatment inflammatory and renal parameters showed no significant differences between two groups. Post-treatment, the combination group showed significantly lower WBC and CRP [WBC (×10⁹/L): 8.2±0.5 vs. 10.9±0.6, CRP (mg/L): 14.0 (5.7, 26.6) vs. 52.1 (24.4, 109.6), both P < 0.05], whereas NEU, PCT, SCr, and BUN levels showed no significant between two groups. ICU length of stay was shorter in the combination group [days: 16 (10, 25) vs. 21 (14, 29), P < 0.05], although mechanical ventilation duration and total hospitalization showed no significant differences between two groups. CONCLUSIONS Intravenous colistin sulfate combined with nebulized inhalation improved clinical efficacy and microbiological clearance in CRO pulmonary infections with an acceptable safety profile.
Humans ; Colistin/therapeutic use* ; Retrospective Studies ; Administration, Inhalation ; Anti-Bacterial Agents/therapeutic use* ; Carbapenems/pharmacology* ; Male ; Female ; Middle Aged ; Gram-Negative Bacteria/drug effects* ; Aged ; Treatment Outcome ; Respiratory Tract Infections/drug therapy*

Objective To study the relationship between serum insulin-like growth factor-1 (IGF-1) and resistin levels and osteoporosis in patients with type 2 diabetes mellitus (T2DM). Methods This study was conducted on 306 T2DM patients admitted to Baoding No.2 Central Hospital from January 2018 to January 2022. According to the detection results of bone mineral density, the patients were divided into osteoporosis group (T≤-2.5) and non-osteoporosis group (T>-2.5). The differences in IGF-1, resistin and bone mineral density were compared between the two groups. Pearson correlation analysis was used to analyze the correlation between serum IGF-1 and resistin levels and bone mineral density in patients with osteoporosis. Receiver operating characteristic (ROC) curve was applied to evaluate the application value of IGF-1 and resistin in predicting osteoporosis in patients with T2DM. Patients with T2DM complicated with osteoporosis were followed up for 2 years, and the occurrence of fractures was assessed. After univariate analysis, multivariate logistic regression analysis was applied to screen the risk factors for fractures in T2DM patients with osteoporosis. Results The incidence rate of osteoporosis in patients with T2DM was 53.59% (164/306). The IGF-1 level and bone mineral density level in the osteoporosis group were lower than those in the non-osteoporosis group, while the level of resistin was higher than that in the non-osteoporosis group (P<0.05). Serum IGF-1 in patients with osteoporosis was positively correlated with bone mineral density, and serum resistin was negatively correlated with bone mineral density (P<0.05). The AUC, sensitivity and specificity of combination of IGF-1 and resistin in predicting osteoporosis were 0.888, 82.93% and 62.68% respectively, which were all higher than those of single factor prediction (P<0.05). The 164 T2DM patients with osteoporosis were followed up for two years, and 15 patients developed fragility fractures, with the incidence of fracture of 9.15% (15/164). Multivariate analysis showed that hypoproteinemia, high-intensity exercise, lack of nutritional management, low IGF-1, and high resistin were risk factors for fractures in patients with T2DM complicated with osteoporosis (P<0.05). Conclusion For patients with T2DM, the incidence rates of osteoporosis and fractures are high. The levels of IGF-1 and resistin are closely related to bone mineral density, which can be combined to predict osteoporosis. Hypoproteinemia, high-intensity exercise, lack of nutritional management, low IGF-1 and high resistin are risk factors for fractures in T2DM patients with osteoporosis. It is necessary to carry out targeted preventive measures in clinical practice to reduce the incidence rate of fractures.

Objective:To investigate the efficacy of two types of micro-focused ultrasound devices combined with botulinum toxin type A (BoNT-A) injection for facial rejuvenation.Methods:A retrospective study was conducted, including 60 female patients aged 28-70 (41.3±7.9) years, who received facial rejuvenation treatment at the Department of Plastic and Reconstructive Surgery, Zhongnan Hospital of Wuhan University, from April 2023 to April 2024. Patients were divided into two groups based on the treatment method: the control group (received only micro-focused ultrasound treatment, n=30) and the combined group (received both micro-focused ultrasound and BoNT-A injection, n=30). Additionally, patients were further categorized into four subgroups based on the type of micro-focused ultrasound device used: Peninsula Microultra? (PM) device group ( n=15), Intelligent Ultrasound? (IU) device group ( n=15), PM device + BoNT-A injection group ( n=15), and IU device + BoNT-A injection group ( n=15). The severity of facial wrinkles was assessed using the wrinkle severity rating scale (WSRS), the Merz aesthetic scale (MAS), and the global aesthetic improvement scale (GAIS) at baseline and 6 months post-treatment. Adverse event rates were also recorded. Results:At 6 months post-treatment, the combined group showed significantly lower WSRS and MAS scores than the control group (both P<0.001). No significant differences were found between the PM and IU device groups, or between the PM + BoNT-A and IU + BoNT-A groups regarding WSRS and MAS scores (all P>0.05). Self-reported GAIS improvement was 56.7% (17/30) for the control group and 80.0% (24/30) for the combined group, with the combined group showing superior results ( P=0.015). The physician-assessed GAIS improvement was 70.0% (21/30) for the control group and 96.7% (29/30) for the combined group, again with the combined group showing superior results ( P=0.007). No significant differences were found in self-reported or physician-assessed GAIS improvement between the PM and IU device groups, or between the PM + BoNT-A and IU + BoNT-A groups (all P>0.05). No severe adverse reactions, such as blisters, scabbing, purpura, bruising, scarring, peripheral facial paralysis, allergies, muscle weakness, dysphagia, or dysphonia, were observed in any patient. Conclusion:The combination of micro-focused ultrasound and BoNT-A injection for facial rejuvenation is more effective than micro-focused ultrasound alone, while there are no significant differences in efficacy between the two micro-focused ultrasound devices.