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

Objective:To analyze the clinical and genetic characteristics of ten Chinese pedigrees affected with 7q11.23 duplication syndrome.Methods:From December 2017 to January 2022, ten pedigrees diagnosed with 7q11.23 duplication syndrome at the First Affiliated Hospital of Zhengzhou University were enrolled as the study subjects. Clinical data of all subjects were collected, and some had subjected to copy number variation sequencing or single nucleotide polymorphism array to analyze the pattern of inheritance.Results:The probands had included six fetuses and four adolescents. Four of the six prenatal cases showed abnormal ultrasound indicators, including three with soft indicators and one with abnomal feta structural development. The clinical phenotype of the four adolescent cases had included mental retardation, delayed language development, and attention deficit hyperactivity disorder. The size of the copy number variations had ranged from 1.31 to 1.42 Mb, involving the classic region of 7q11.23 duplication syndrome. Of these, five cases had undergone parental origin testing, three cases were de novo, and two were hereditary. Conclusion:Individuals with 7q11.23 duplication syndrome may show substantial clinical phenotypic heterogeneity, hence the affected families should be provided with pre-pregnancy consultation and reproductive guidance.

To study the correlation between the level of Bordetella pertussis nucleic acid and clinical features of the disease in infants and young children and to investigate the risk factors for the development of severe pertussis. Using retrospective research methods, children aged 1 month-3 years who came to Hunan Children′s Hospital from August 2023 to February 2024 and were diagnosed with pertussis for analysis. According to the logarithmic value of BP-DNA (log 10 copies/ml), 35 cases were divided into the low load group, 78 cases were divided into the medium load group and 94 cases were divided into the high load group; 54 cases were divided into the severe whooping cough group and 153 cases were divided into the general group according to the severity of the disease; the clinical characteristics and laboratory data of the groups were compared, and the risk factors for the occurrence of severe whooping cough were analyzed at the same time. The ROC was used to evaluate the predictive efficacy of BP-DNA and WBC count for the development of severe pertussis. The results showed that in the high-dose group, the WBC count(22.59×10 9/L), L/N ratio(3.31), and hospitalization days(9.0 d) were significantly higher than those in the medium-dose group and low-dose group ( F=6.309, 2.825, 15.149, all P<0.05). The hospitalization rate (100%), combined infection rate (64.96%), incidence of severe whooping cough (31.9%), pyrexia rate (29.8%), and corticosteroid use rate (57.4%) were also significantly higher than the other two groups ( χ2=25.977, 9.163, 9.371, 8.299, 20.332, all P<0.05), and the complete immunity rate (9.6%) was significantly lower than the other two groups ( χ2=11.632, P<0.05). Compared with the group of common whooping cough, the proportion of children under 1 year old (100%, χ2=9.581), the BP-DNA load (6.56 log 10 copies/ml, Z=4.004), the WBC count(31.34×10 9/L, t=7.513), the PCT level(0.07 ng/ml, Z=2.626), the IL-6 level (6.65 ng/ml, Z=4.336), the combined infection rate (88.9%, χ2=36.536), the incidence of wheezing or dyspnea (55.6%, χ2=42.972), the rate of no improvement of symptoms with macrolides prior to the visit (77.8%, χ2=26.266), and the incidence of fever (55.6%, χ2=42.972) were all significantly higher;the complete immunity rate was significantly lower (5.6%, χ2=9.581) in the severe whooping cough group, the differences were all statistically significant(all P<0.05).The result of logistic regression analysis showed severe elevation of BP-DNA, high leukocyte count, co-infection, wheezing or shortness of breath, pyrexia and no improvement of symptoms with macrolides before the treatment were the risk factors for the development of severe pertussis and the logistic regressive model predicts a sensitivity and specificity of 0.83 and 0.90 for severe whooping cough, respectively. The sensitivity of BP-DNA>1.91×10 6 copies/ml, WBC count >19.97×10 9/L and the binominal combined test to predict the occurrence of severe pertussis were 0.87, 0.61 and 0.80, and the specificity were 0.43, 0.86 and 0.73, respectively. In conclusion, nucleic acid load in infants with pertussis correlated with clinical characteristics such as the active immunity status, fever, co-infections and hospitalisation and days in hospital. Children with high nucleic acid load, high white blood cell counts, co-infections, fever and no improvement of symptoms with macrolides prior to seeing a doctor were more likely to develop the severe pertussis. When BP-DNA >1.91×10 6 copies/ml or WBC counts>19.97×10 9/L, they have the highest predictive efficacy for severe pertussis respectively, and combined detection is better.

To study the correlation between the level of Bordetella pertussis nucleic acid and clinical features of the disease in infants and young children and to investigate the risk factors for the development of severe pertussis. Using retrospective research methods, children aged 1 month-3 years who came to Hunan Children′s Hospital from August 2023 to February 2024 and were diagnosed with pertussis for analysis. According to the logarithmic value of BP-DNA (log 10 copies/ml), 35 cases were divided into the low load group, 78 cases were divided into the medium load group and 94 cases were divided into the high load group; 54 cases were divided into the severe whooping cough group and 153 cases were divided into the general group according to the severity of the disease; the clinical characteristics and laboratory data of the groups were compared, and the risk factors for the occurrence of severe whooping cough were analyzed at the same time. The ROC was used to evaluate the predictive efficacy of BP-DNA and WBC count for the development of severe pertussis. The results showed that in the high-dose group, the WBC count(22.59×10 9/L), L/N ratio(3.31), and hospitalization days(9.0 d) were significantly higher than those in the medium-dose group and low-dose group ( F=6.309, 2.825, 15.149, all P<0.05). The hospitalization rate (100%), combined infection rate (64.96%), incidence of severe whooping cough (31.9%), pyrexia rate (29.8%), and corticosteroid use rate (57.4%) were also significantly higher than the other two groups ( χ2=25.977, 9.163, 9.371, 8.299, 20.332, all P<0.05), and the complete immunity rate (9.6%) was significantly lower than the other two groups ( χ2=11.632, P<0.05). Compared with the group of common whooping cough, the proportion of children under 1 year old (100%, χ2=9.581), the BP-DNA load (6.56 log 10 copies/ml, Z=4.004), the WBC count(31.34×10 9/L, t=7.513), the PCT level(0.07 ng/ml, Z=2.626), the IL-6 level (6.65 ng/ml, Z=4.336), the combined infection rate (88.9%, χ2=36.536), the incidence of wheezing or dyspnea (55.6%, χ2=42.972), the rate of no improvement of symptoms with macrolides prior to the visit (77.8%, χ2=26.266), and the incidence of fever (55.6%, χ2=42.972) were all significantly higher;the complete immunity rate was significantly lower (5.6%, χ2=9.581) in the severe whooping cough group, the differences were all statistically significant(all P<0.05).The result of logistic regression analysis showed severe elevation of BP-DNA, high leukocyte count, co-infection, wheezing or shortness of breath, pyrexia and no improvement of symptoms with macrolides before the treatment were the risk factors for the development of severe pertussis and the logistic regressive model predicts a sensitivity and specificity of 0.83 and 0.90 for severe whooping cough, respectively. The sensitivity of BP-DNA>1.91×10 6 copies/ml, WBC count >19.97×10 9/L and the binominal combined test to predict the occurrence of severe pertussis were 0.87, 0.61 and 0.80, and the specificity were 0.43, 0.86 and 0.73, respectively. In conclusion, nucleic acid load in infants with pertussis correlated with clinical characteristics such as the active immunity status, fever, co-infections and hospitalisation and days in hospital. Children with high nucleic acid load, high white blood cell counts, co-infections, fever and no improvement of symptoms with macrolides prior to seeing a doctor were more likely to develop the severe pertussis. When BP-DNA >1.91×10 6 copies/ml or WBC counts>19.97×10 9/L, they have the highest predictive efficacy for severe pertussis respectively, and combined detection is better.

Background::Hypothermia therapy has been suggested to attenuate myocardial necrosis; however, the clinical implementation as a valid therapeutic strategy has failed, and new approaches are needed to translate into clinical applications. This study aimed to assess the feasibility, safety, and efficacy of a novel selective intracoronary hypothermia (SICH) device in mitigating myocardial reperfusion injury.Methods::This study comprised two phases. The first phase of the SICH was performed in a normal porcine model for 30 minutes ( n = 5) to evaluate its feasibility. The second phase was conducted in a porcine myocardial infarction (MI) model of myocardial ischemia/reperfusion which was performed by balloon occlusion of the left anterior descending coronary artery for 60 minutes and maintained for 42 days. Pigs in the hypothermia group ( n = 8) received hypothermia intervention onset reperfusion for 30 minutes and controls ( n = 8) received no intervention. All animals were followed for 42 days. Cardiac magnetic resonance analysis (five and 42 days post-MI) and a series of biomarkers/histological studies were performed. Results::The average time to lower temperatures to a steady state was 4.8 ± 0.8 s. SICH had no impact on blood pressure or heart rate and was safely performed without complications by using a 3.9 F catheter. Interleukin-6 (IL-6), tumor necrosis factor-α, C-reactive protein (CRP), and brain natriuretic peptide (BNP) were lower at 60 min post perfusion in pigs that underwent SICH as compared with the control group. On day 5 post MI/R, edema, intramyocardial hemorrhage, and microvascular obstruction were reduced in the hypothermia group. On day 42 post MI/R, the infarct size, IL-6, CRP, BNP, and matrix metalloproteinase-9 were reduced, and the ejection fraction was improved in pigs that underwent SICH.Conclusions::The SICH device safely and effectively reduced the infarct size and improved heart function in a pig model of MI/R. These beneficial effects indicate the clinical potential of SICH for treatment of myocardial reperfusion injury.

Objective:To evaluate the effect of accelerated rehabilitation surgery (ERAS) under diagnosis-intervention packet (DIP) in patients with early cancer of digestive tract undergoing endoscopic submucosal dissection (ESD).Methods:The 64 patients with early cancer of digestive tract treated with ESD in the Gastroenterology Department of the Second People′s Hospital of Jiaozuo were selected by randomized controlled trial and convenient sampling method. According to random number table method, they were divided into routine group and observation group, 32 patients in each group. All patients in the 2 groups paid their medical expenses by DIP method, the routine group was treated with traditional perioperative nursing, and the observation group was treated with ERAS perioperative management mode. The postoperative complication rate, length of hospital stay, DIP allocation ratio, and patient satisfaction with nursing were compared between the two groups.Results:There were 16 men and women in the routine group, 14 men and 18 women in the observation group.After intervention, the incidence of postoperative complications was 21.88% (7/32) in the routine group and 3.12% (1/32) in the observation group, and the difference between the two groups was statistically significant ( χ2=5.14, P<0.05). The length of stay was (10.93 ± 2.87) d in the routine group and (9.01 ± 1.53) d in the observation group, and the difference between the two groups was statistically significant ( t=4.13, P<0.05). The average hospitalization expenses per case was (20 108.23 ± 6 495.49) yuan in the routine group and (18 589.03 ± 4 439.46) yuan in the observation group, and the difference between the two groups was statistically significant ( t=20.57, P<0.05). The DIP allocation ratio of the observation group was 87.98% (303 419.26/344 872.99), and that of the routine group was 69.33% (244 864.99/353 187.65), and the difference between the two groups was statistically significant ( χ2=4.81, P<0.05). The satisfaction of the observation group was 96.88% (31/32) and the routine group was 78.13% (25/32), and the difference between the two groups was statistically significant ( χ2=5.14, P<0.05). Conclusions:The accelerated rehabilitation surgical nursing can effectively reduce the postoperative complications, the average length of stay, the average hospitalization expenses per case under DIP in patients with early cancer of digestive tract treated by ESD, improve the DIP allocation ratio of ESD diseases and the patient′s nursing satisfaction, which reflects the value of nursing work and can be applied to the nursing management of other surgical diseases.

BACKGROUND:Epigenetics,as an important regulation mode of gene expression network,has been proved to play an important role in the occurrence and development of aortic aneurysm mediated by vascular smooth muscle cell remodeling. OBJECTIVE:To review the epigenetic regulation mechanism underlying vascular smooth muscle cell remodeling during the occurrence and progression of aortic aneurysm. METHODS:Related articles published from 1970 to 2022 were retrieved from PubMed,Web of Science and CNKI databases.The keywords were"Aortic aneurysm,Vascular smooth muscle,Smooth muscle cells,Epigenetic,DNA methylation,Histone modification,Non coding RNA"in English and Chinese.Ultimately,we included 71 articles for review. RESULTS AND CONCLUSION:Epigenetic modification can influence the occurrence and progression of aortic aneurysm by targeting vascular smooth muscle cell remodeling and extracellular matrix degradation.Targeted epigenetic modification can play a key role in aortic aneurysm treatment,delaying the disease and improving the prognosis.Epigenetic related enzymes,such as DNA methylesterases and histone-modifying enzymes,can influence the progression of aortic aneurysm by regulating vascular smooth muscle cell remodeling,including cell proliferation,migration and apoptosis,and can be used as targets for drug therapy.The research of epigenetic modification on aortic aneurysm is still in the basic research stage and some epigenetic modification mechanisms have not yet been explored.With the development of medical research,targeted epigenetic modification is expected to achieve new breakthroughs in the treatment of aortic aneurysm and clinical transformation.

Objective To investigate the impact of anti-reflux modified duodenal exclusion surgery on glucose metabolism in rats with type 2 diabetes mellitus (T2DM), and to elucidate the role of the duodenum in maintaining glucose homeostasis. MethodsForty male Sprague-Dawley rats aged 5 weeks were fed a high-fat diet and induced with T2DM using low-dose streptozotocin. Thirty-six rats that met the T2DM model criteria were randomly divided into three groups: the simple duodenal exclusion surgery group (DE group), the anti-reflux modified duodenal exclusion group (MDE group), and the sham operation group (SO group), with 12 rats in each group. Gastroenterography was performed 4 weeks after surgery, and the body weight, fasting blood glucose levels, and serum glucagon-like peptide-1 (GLP-1) concentrations were measured before surgery and at 1, 2, 4, and 8 weeks post-surgery. Eight weeks post-surgery, the rats were euthanized, and a 1 cm segment of the biliopancreatic loop was collected from each group for pathological sectioning and HE staining to observe the intestinal mucosal villus length under an optical microscope. Results Gastroenterography showed that there was significant reflux of the contrast agent into the duodenal lumen in the DE group, while no reflux was observed in the MDE group. At one week post-surgery, the body weights of rats in all three groups significantly decreased compared to before surgery (P<0.05), and then the body weights of all groups increased over time, with no significant differences between the groups (P>0.05). Compared with the SO group, the fasting blood glucose levels in the MDE and DE groups significantly decreased at all time points post-surgery (P<0.05), while GLP-1 concentrations significantly increased (P<0.05). The fasting blood glucose levels in the MDE group were lower than those in the DE group at all time points post-surgery (P<0.05), but there were no significant differences in serum GLP-1 concentrations between the MDE and DE groups (P>0.05). Regarding intestinal mucosal morphology, the villus lengths of the biliopancreatic loops in the MDE group were significantly shorter than those in the DE and SO groups (P<0.05). Conclusion Anti-reflux modified duodenal exclusion surgery effectively improves glucose metabolism in T2DM rats by preventing the reflux of chyme into the diverted duodenum, thereby enhancing its hypoglycemic effect.

Metastasis accounts for 90% of breast cancer deaths, where the lethality could be attributed to the poor drug accumulation at the metastatic loci. The tolerance to chemotherapy induced by breast cancer stem cells (BCSCs) and their particular redox microenvironment further aggravate the therapeutic dilemma. To be specific, therapy-resistant BCSCs can differentiate into heterogeneous tumor cells constantly, and simultaneously dynamic maintenance of redox homeostasis promote tumor cells to retro-differentiate into stem-like state in response to cytotoxic chemotherapy. Herein, we develop a specifically-designed biomimic platform employing neutrophil membrane as shell to inherit a neutrophil-like tumor-targeting capability, and anchored chemotherapeutic and BCSCs-differentiating reagents with nitroimidazole (NI) to yield two hypoxia-responsive prodrugs, which could be encapsulated into a polymeric nitroimidazole core. The platform can actively target the lung metastasis sites of triple negative breast cancer (TNBC), and release the escorted drugs upon being triggered by the hypoxia microenvironment. During the responsiveness, the differentiating agent could promote transferring BCSCs into non-BCSCs, and simultaneously the nitroimidazole moieties conjugated on the polymer and prodrugs could modulate the tumor microenvironment by depleting nicotinamide adenine dinucleotide phosphate hydrogen (NADPH) and amplifying intracellular oxidative stress to prevent tumor cells retro-differentiation into BCSCs. In combination, the BCSCs differentiation and tumor microenvironment modulation synergistically could enhance the chemotherapeutic cytotoxicity, and remarkably suppress tumor growth and lung metastasis. Hopefully, this work can provide a new insight in to comprehensively treat TNBC and lung metastasis using a versatile platform.

As a neurological disorder in the brain, epilepsy is not only associated with abnormal synchronized discharging of neurons, but also inseparable from non-neuronal elements in the altered microenvironment. Anti-epileptic drugs (AEDs) merely focusing on neuronal circuits frequently turn out deficient, which is necessitating comprehensive strategies of medications to cover over-exciting neurons, activated glial cells, oxidative stress and chronic inflammation synchronously. Therefore, we would report the design of a polymeric micelle drug delivery system that was functioned with brain targeting and cerebral microenvironment modulation. In brief, reactive oxygen species (ROS)-sensitive phenylboronic ester was conjugated with poly-ethylene glycol (PEG) to form amphiphilic copolymers. Additionally, dehydroascorbic acid (DHAA), an analogue of glucose, was applied to target glucose transporter 1 (GLUT1) and facilitate micelle penetration across the blood‒brain barrier (BBB). A classic hydrophobic AED, lamotrigine (LTG), was encapsulated in the micelles via self-assembly. When administrated and transferred across the BBB, ROS-scavenging polymers were expected to integrate anti-oxidation, anti-inflammation and neuro-electric modulation into one strategy. Moreover, micelles would alter LTG distribution in vivo with improved efficacy. Overall, the combined anti-epileptic therapy might provide effective opinions on how to maximize neuroprotection during early epileptogenesis.