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.

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.

Malignant tumors are one of the main causes of death from chronic diseases in China,and their incidence and mortality rates show an in-creasing trend year by year.Advanced non-surgical treatment of malignant tumors is an important means of improving patients'prognosis and en-hancing their quality of life.The traditional Chinese medicine Ganoderma lucidum has anti-tumor ef-fects and plays a role in the treatment of many ma-lignant tumors.In this paper,a systematic review of the effects of Ganoderma lucidum active ingredi-ents on tumors has been conducted at home and abroad in the past five years to explore the anti-tu-mor mechanism of Ganoderma lucidum active in-gredients and to lay a theoretical foundation for the application of Ganoderma lucidum active ingre-dients in clinical practice.

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.

Background Formaldehyde and benzene homologues are common environmental pollutants, and their neurotoxicity has aroused widespread concern. Objective To investigate the effect of taurine on cognitive impairment after exposure to formaldehyde and benzene analogues in young rats. Methods Twenty four-week old SD rats were randomly divided into four groups, with six rats in each group: control group (clean air), model group (5 mg·m⁻³ formaldehyde + 5 mg·m⁻³ benzene + 10 mg·m⁻³ toluene + 10 mg·m⁻³ xylene), low-dose taurine intervention group (5 g·L⁻¹ taurine + mixture of formaldehyde and benzene analogues), and high-dose taurine intervention group (10 g·L⁻¹ taurine + formaldehyde and mixture of benzene analogues), and the exposure was administered by oral and nasal aerosol inhalation for 28 d. At the end of exposure, the learning and memory ability of rats in each group was measured by Morris water maze test. After the behavioral test, the rats were anesthetized and neutralized, and the brain tissue was harvested for histopathological and molecular biological tests. The apoptosis rate of neurons in hippocampal CA1 area was detected by Tunel assay, and the expression levels of apoptosis-related proteins such as caspase 3, bax, and bcl-2 in hippocampal tissue were detected by Western blotting. Results The growth and development of rats in each group were good during inhalation. During the Morris water maze experiment, the escape latencies of rats in the taurine intervention groups were not different from that in the control group (P>0.05) from day 3 to day 5 of training, while the escape latency of rats in the model group was significantly higher than that in the control group (P <0.05). The number of crossing platform and the target quadrant residence time in the high-dose taurine intervention group were not different from those in the control group (P>0.05), while the two variables in the model group and low-dose taurine intervention group were significantly lower than those in the control group (P <0.05). The apoptotic rates of neurons in the hippocampal CA1 area of rats in the control group, model group, and low-dose and high-dose taurine intervention groups were 5.11%, 18.87%, 9.39%, and 4.63%, respectively. The apoptotic rate in the model group was higher than those in the control group and low-dose and high-dose taurine intervention groups (P<0.05). The expression levels of caspase 3, bax, and bcl-2 in the hippocampus of rats in the low-dose and high-dose taurine intervention groups showed no difference compared with the control group (P>0.05). The expression levels of caspase 3 and bax in the model group were higher than those in the control group and low-dose or high-dose taurine intervention groups (P<0.05), and the expression levels of bcl-2 was lower (P<0.05). Conclusion The mixed exposure to formaldehyde and benzene analogues can damage the learning and memory ability of young rats, and increase the apoptosis of neurons in hippocampal CA1 region. Taurine can reverse the damage induced by formaldehyde and benzene analogues.

Objective:To investigate factors associated with acute kidney injury(AKI) in postoperative colorectal cancer patients.Methods:The clinical data of 376 colorectal carcinoma (CRC) patients at Department of General Surgery, Affiliated Cancer Hospital of Zhengzhou University from Jan 2018 to Jun 2021 were retrospectively analyzed. Patients were divided into acute kidney injury (AKI) ( n=29) and non-AKI groups ( n=347). The demographic information, perioperative status, laboratory results and other relevant data of the two groups were compared . Binary logistic regression was used to analyze the independent risk factors for postoperative AKI. Results:Twenty-nine CRC patients (7.7%) had postoperative AKI. Binary Logistic regression analysis showed that preoperative hypertension ( OR=3.487, 95% CI: 1.081-11.251, P=0.037), anemia ( OR=3.158, 95% CI: 1.114-8.953, P=0.031), inadequate intraoperative crystalloid infusion ( OR=0.998, 95% CI: 0.997-0.999, P=0.007), low intraoperative mean arterial pressure ( OR=0.915, 95% CI: 0.863-0.970, P=0.003) and moderate to severe postoperative decline in hemoglobin levels ( OR=4.105, 95% CI: 1.487-11.335, P=0.006) were independent risk factors. Conclusion:Preoperative hypertension, anemia, inadequate intraoperative crystalloid infusion, low intraoperative mean arterial pressure, and moderate to severe postoperative decline in hemoglobin levels were independent risk factors for AKI development in colorectal cancer patients.

【Objective】 To investigate the predictive value of nutritional risk index (NRI), systemic immune inflammatory index (SⅡ) and triglyceride glucose (TyG) index on the condition and prognosis of patients with acute pancreatitis (AP). 【Methods】 A total of 173 AP patients were divided into mild acute pancreatitis (MAP) group (n=79), moderate acute pancreatitis (MSAP) group (n=44), and severe acute pancreatitis (SAP) group (n=50) according to their severity. All the 50 SAP patients were divided into death group (19 cases) and survival group (31 cases) according to the death situation. The NRI, SⅡ and TyG indexes of each group were recorded and compared. The values of NRI, SⅡ and TyG index in predicting the occurrence and death of SAP were analyzed with ROC curve. Pearson correlation analysis of the correlation between NRI, SⅡ, and TyG index in SAP patients was made. 【Results】 NRI was significantly lower in SAP group (89.25±4.50) than in MSAP group (93.40±6.25) and MAP group (97.62±8.60), while SⅡand TyG index in SAP group (2 706.30±1 052.74, 7.84±1.21) were significantly higher than those in MSAP group (1 937.24±983.48, 6.52±1.05) and MAP group (1 280.58±717.36, 4.65±0.58) (P<0.001). NRI in death group (86.40±3.70) was significantly lower than that in survival group (91.46±5.28), while SⅡ and TyG index in death group (3 085.73±1 192.48, 9.05±1.37) were significantly higher than those in survival group (2 270.26±994.53, 6.70±1.10) (P<0.001). The ROC curve showed that the AUC of NRI, SⅡ and TyG index jointly predicting SAP occurrence and death was 0.850 (95% CI: 0.792-0.908) and 0.905 (95% CI: 0.843-0.966), respectively. Correlation analysis showed that NRI was negatively correlated with SⅡ and TyG index in SAP patients (r=-0.761, P<0.001, r=-0.813, P<0.001), while SⅡ was positively correlated with TyG index (r=0.842, P<0.001). 【Conclusion】 NRI, SⅡ and TyG index are related to the severity and death of AP patients, and the combination of the three indexes has good value in predicting the occurrence and prognosis of SAP.

Objective To observe the value of multimodal imaging for diagnosis of cardiac space-occupying lesions.Methods Data of 70 patients with cardiac space-occupying lesions who underwent echocardiography and cardiac CT(CCT)were retrospectively analyzed,among them 35 also underwent cardiac MRI(CMRI).The value of multimodal imaging for diagnosis of cardiac space-occupying lesions were explored according to the results of surgical pathology or clinical diagnosis.Results Among 70 cases,benign tumors were confirmed by surgical pathology in 43 cases,while malignant tumors were confirmed by surgical pathology in 3 cases and clinically diagnosed in 1 case.Meanwhile,non-tumor-occupying lesions were clinically diagnosed in 23 cases,all obviously shrunken after treatments.Among 70 cases,echocardiography correctly diagnosed 57 cases,misdiagnosed 8 cases and unclearly diagnosed 5 cases,with diagnostic accuracy rate of 81.43%(57/70).CCT correctly diagnosed 63 cases,misdiagnosed 4 cases but missed 3 cases,with diagnostic accuracy rate of 90.00%(63/70).CMRI outcomes in all 35 cases were consistent with surgical pathologic results,with diagnostic accuracy rate of 100%(35/35).Conclusion Multimodal imaging might provide objective evidences for diagnosis and treatment of cardiac space-occupying lesions.