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 investigate the effect and mechanism of Panax notoginseng saponins （PNS） on wound healing after anal fistula surgery in rats by regulating the hypoxia-inducible factor-1α （HIF-1α）/vascular endothelial growth factor （VEGF）/ vascular endothelial growth factor receptor-2 （VEGFR2） signaling pathway. METHODS SD rats were selected to establish a postoperative rat model of anal fistula by infecting wound with Escherichia coli. The model rats were randomly grouped into model group， PNS low-dose and high-dose groups （15， 30 mg/cm2）， high-dose of PNS+2-methoxyestradiol （2ME2） group （PNS 30 mg/cm2+HIF-1α inhibitor 2ME2 4 mg/kg）， with 10 rats in each group. Another 10 normal rats were selected for back hair removal treatment as the control group. Each drug group was injected with the corresponding drug solution intramuscularly or （and） intraperitoneally， once a day， for 3 weeks. After the last administration， the wound healing rate （excluding the control group）， microvascular density （MVD）， the expression of collagen Ⅰ and fibronectin （FN） in the wound tissue were detected in each group； the levels of angiogenic factors [VEGF， E-mail：842710813@qq.com angiopoietin-Ⅰ （Ang-Ⅰ）， Ang-Ⅱ] in serum， the levels of inflammatory factors [interleukin-6 （IL-6） and IL-2] in serum binggui7183@163.com and wound tissue as well as the expressions of the related proteins of HIF-1α/VEGF/VEGFR2 signaling pathway in the wound tissue of rats were also detected in each group. RESULTS The MVD， the expression of collagen Ⅰ and FN in the wound tissue， and the levels of IL-6 and IL-2 in serum and wound tissue of rats increased significantly in the model group， compared to the control group （P＜0.05）， while the serum levels of VEGF， Ang- Ⅰ and Ang-Ⅱ decreased significantly （P＜0.05）. The wound healing rate， the MVD in wound tissue， the serum levels of VEGF， Ang-Ⅰ and Ang-Ⅱ， the expressions of collagen Ⅰ and FN in the wound tissue， and protein expressions of HIF-1α， VEGF and VEGFR2 in the PNS low-dose and high-dose groups increased significantly， compared to the model group （P＜0.05）， while the levels of IL-6 and IL-2 in serum and wound tissue decreased significantly （P＜0.05）； the high-dose PNS had a stronger effect （P＜ 0.05）. 2ME2 could weaken the effect of PNS on above indicators of rats after anal fistula surgery （P＜0.05）. CONCLUSIONS PNS can promote the production of angiogenic factors and inhibit the production of pro-inflammatory factors， thereby promoting wound healing in rats after anal fistula surgery. The above effects are related to the activation of HIF-1α/VEGF/VEGFR2 signaling pathway.

In recent years， data mining algorithms have been widely employed in scientific research within the field of traditional Chinese medicine （TCM）. The data mining algorithms are used to effectively handle and analyze the complex data in TCM formulas， providing a rational explanation for the mechanism of action. This method has proven particularly useful in uncovering patterns of compatibility and frequent combinations of herbs in TCM， thereby enhancing the reliability and accuracy of clinical diagnosis， target screening， and the study of new drugs. This paper reviews and analyzes 147 papers on TCM formula research that utilize data mining algorithms. The results indicate that data mining algorithms play a unique advantage in six sub- areas， including the study on the mechanism of action in TCM formula， the dose-efficacy of TCM formulas， the identification of core drugs pairs/groups， mining the relationships among “formulas-drug-symptom”， the discovery of new formulas， and mining the compatibility law. Notably， association rules and clustering algorithms are the most representative.

Gliomas are the most common central nervous system tumours; they are highly aggressive and have a poor prognosis. RGS16 belongs to the regulator of G-protein signalling (RGS) protein family, which plays an important role in promoting various cancers, such as breast cancer, pancreatic cancer, and colorectal cancer. Moreover, previous studies confirmed that let-7c-5p, a well-known microRNA, can act as a tumour suppressor to regulate the progression of various tumours by inhibiting the expression of its target genes. However, whether RGS16 can promote the progression of glioma and whether it is regulated by miR let-7c-5p are still unknown. Here, we confirmed that RGS16 is upregulated in glioma tissues and that high expression of RGS16 is associated with poor survival. Ectopic deletion of RGS16 significantly suppressed glioma cell proliferation and migration both in vitro and in vivo. Moreover, RGS16 was validated as a direct target gene of miR let-7c-5p. The overexpression of miR let-7c-5p obviously downregulated the expression of RGS16, and knocking down miR let-7c-5p had the opposite effect. Thus, we suggest that the suppression of RGS16 by miR let-7c-5p can promote glioma progression and may serve as a potential prognostic biomarker and therapeutic target in glioma.
Humans ; Phosphatidylinositol 3-Kinases/metabolism* ; Proto-Oncogene Proteins c-akt/metabolism* ; MicroRNAs/metabolism* ; Glioma/genetics* ; Genes, Tumor Suppressor ; Cell Proliferation ; Gene Expression Regulation, Neoplastic ; Cell Line, Tumor

Objective To evaluate the effect of donor age on short-term survival of patients with idiopathic pulmonary fibrosis (IPF) after lung transplantation. Methods Clinical data of 235 IPF donors and recipients of lung transplantation were retrospectively analyzed. Univariate and multivariate Cox proportional hazard regression models were employed to analyze the correlation between donor age and short-term mortality rate of IPF patients after lung transplantation. Kaplan-Meier was used to draw the survival curve. Results Univariate Cox regression analysis showed that donor age was correlated with the 1-year fatality of IPF patients after lung transplantation. The 1-year fatality of recipients after lung transplantation was increased by 0.020 times if donor age was increased by 1 year (P=0.009). Oxygenation index of the donors, preoperative oxygenation index, preoperative lung allocation score, preoperative N-terminal pro brain natriuretic peptide, pattern of transplantation, pattern of intraoperative extracorporeal membrane oxygenation and intraoperative blood transfusion volume of the recipients were correlated with 1-year fatality after lung transplantation (all P < 0.1). Multivariate Cox regression analysis demonstrated that there was no correlation between donor age and 30-, 90-, 180-d and 1-year fatality of IPF patients after lung transplantation (all P > 0.05). Sensitivity analysis showed that there was no significant difference in 30-, 90-, 180-d and 1-year fatality after lung transplantation among donors aged < 18, 18-33, 34-49 and ≥50 years (all P > 0.05). Conclusions Donor age exerts no effect upon short-term survival of IPF patients after lung transplantation. Considering the mechanical ventilation time, oxygenation index, infection and other factors of donors, the age range of lung transplant donors may be expanded.

The clinical features, examination findings and genetic testing results of a newborn with neurobehavioral developmental abnormality caused by the PAK3 gene mutation in the Department of Neonatology, Anhui Provincial Children′s Hospital were retrospectively analyzed in November 11, 2021.The male 9-day-old newborn presented with the difficult-to-wean for 9 days after birth.The child had repeated startle reflexes, decreased muscle tension in the extremities, and partial primitive reflexes.Amplitude-integrated electroencephalogram (aEEG) showed the lower and upper boundary voltage of 10 μV and 40 μV, respectively.Obvious mature sleep-wake cycles were not found, and 2 electric seizures were recorded.The aEEG suggested the moderate-to-severe abnormal aEEG.Magnetic resonance imaging showed that the corpus callosum was slightly thinner.The family-centered diagnostic exosome sequencing showed a missense mutation of the PAK3 gene[c.1327 (exon18) G>A, p.G443R], which has not been previously reported at home and abroad.This case enriched the clinical phenotype of the PAK3 gene mutation and suggested the potential value of whole genome sequencing in clinical diagnosis and genetic guidance.

OBJECTIVE To explore the effects of pterostilbene （PTE） on wound healing in diabetic skin ulcer model rats and its mechanism. METHODS Ten SD rats were grouped into control group； after diabetic skin ulcer model of other rats was induced by giving high-fat and high-sugar diet+intraperitoneal injection of streptozotocin+cutting off the skin and subcutaneous tissue in the marked area of the back， model rats were randomly divided into model group， PTE low-dose group （40 mg/kg）， PTE high-dose group （80 mg/kg）， PTE high-dose+PP2 group （80 mg/kg PTE+2 mg/kg SRC inhibitor PP2）， with 10 rats in each group. On the second day after modeling， the rats in each drug group were intraperitoneally injected with corresponding drug solutions， while the rats in control group and model group were intraperitoneally injected with normal saline， once a day， for 14 consecutive days. The wound healing rate of rats in each group was measured on the 7th and 14th day of administration； the contents of interleukin-1β （IL-1β）， IL-6， tumor necrosis factor-α （TNF-α） and vascular endothelial growth factor （VEGF） in the serum of rats were detected； the pathological changes of wound granulation tissue were observed， and the expressions of SRC/mitogen-activated protein kinase kinase （MEK）/extracellular signal-regulated kinase （ERK） signaling pathway-related proteins in wound granulation tissue were detected. RESULTS Compared with control group， the wound healing rate， serum content of VEGF， the phosphorylation levels of SRC， MEK1/2 and ERK1/2 were decreased significantly （P＜0.05）， while serum contents of IL- 1β， IL-6 and TNF-α were increased significantly （P＜0.05）； there was obvious infiltration of inflammatory cells in the wound granulation tissue， and the number of new blood vessels decreased. Compared with model group， above indexes of PTE low-dose and high-dose groups were improved significantly （P＜0.05）， and the pathological injury of granulation tissue in wound was improved. PP2 significantly reversed the improvement effects of PTE on the above indexes （P＜0.05）. CONCLUSIONS PTE can promote the wound healing of diabetic skin ulcer model rats， the mechanism of which may be related to activating SRC/MEK/ERK signaling pathway.

OBJECTIVE: To evaluate the application of surgical strategies for the treatment of cervical ossification of the posterior longitudinal ligament (OPLL) involving the C ₂ segment. METHODS: The literature about the surgery for cervical OPLL involving C ₂ segment was reviewed, and the indications, advantages, and disadvantages of surgery were summarized. RESULTS: For cervical OPLL involving the C ₂ segments, laminectomy is suitable for patients with OPLL involving multiple segments, often combined with screw fixation, and has the advantages of adequate decompression and restoration of cervical curvature, with the disadvantages of loss of cervical fixed segmental mobility. Canal-expansive laminoplasty is suitable for patients with positive K-line and has the advantages of simple operation and preservation of cervical segmental mobility, and the disadvantages include progression of ossification, axial symptoms, and fracture of the portal axis. Dome-like laminoplasty is suitable for patients without kyphosis/cervical instability and with negative R-line, and can reduce the occurrence of axial symptoms, with the disadvantage of limited decompression. The Shelter technique is suitable for patients with single/double segments and canal encroachment >50% and allows for direct decompression, but is technically demanding and involves risk of dural tear and nerve injury. Double-dome laminoplasty is suitable for patients without kyphosis/cervical instability. Its advantages are the reduction of damage to the cervical semispinal muscles and attachment points and maintenance of cervical curvature, but there is progress in postoperative ossification. CONCLUSION OPLL involving the C ₂ segment is a complex subtype of cervical OPLL, which is mainly treated through posterior surgery. However, the degree of spinal cord floatation is limited, and with the progress of ossification, the long-term effectiveness is poor. More research is needed to address the etiology of OPLL and to establish a systematic treatment strategy for cervical OPLL involving the C ₂ segment.
Humans ; Longitudinal Ligaments/surgery* ; Ossification of Posterior Longitudinal Ligament/surgery* ; Treatment Outcome ; Osteogenesis ; Decompression, Surgical/methods* ; Cervical Vertebrae/surgery* ; Laminoplasty/methods* ; Kyphosis/surgery* ; Retrospective Studies

Objective:To explore the effect of acute kidney injury(AKI)on near-term survival after lung transplantation(LT)in patients with idiopathic pulmonary fibrosis(IPF).Methods:Through consulting electronic medical records, anesthetic modes and Chinese Lung Transplant Registration System, clinical data are retrospectively reviewed for 275 IPF patients undergoing LT at Affiliated Wuxi People's Hospital of Nanjing Medical University from January 2017 to April 2021.According to the diagnostic criteria of Kidney Disease: Improving Global Outcomes(KDIGO), they are divided into two groups of AKI(169 cases)and non-AKI(106 cases).Perioperative findings of two groups are recorded.Then univariate and multivariate Cox regression models are employed for determining whether or not inter-group differences existed in survival rates post-LT.Also AKI is staged according to the KDIGO.And the effect of stage 1/2/3 AKI on near-term postoperative prognosis is examined.Results:The differences are significantly different in recipient gender, creatinine, 6-minute walking test, forced vital capacity(FVC), lung allocation score, oxygenation index, N-terminal pro-brain natriuretic peptide(NT-Pro BNP), preoperative hormone use and volume of crystal infusion( P<0.05).After multivariate Cox regression correcting for covariates, no statistical significance exists in effect of AKI stage 1 on near-term postoperative survival rate( P<0.05).AKI stage 2/3 still has statistical significance in risk of mortality at Day 30/90/180/365 post-operation( P>0.05). Conclusions:As a common complication post-LT, AKI significantly affects near-term postoperative prognosis of transplant IPF patients.Stage 2/3 AKI impacts near-term postoperative survival while stage 1 AKI is not associated with higher mortality.

Objective:To investigate the risk factors of early death after lung transplantation in patients with idiopathic pulmonary fibrosis (IPF) complicated with pulmonary arterial hypertension (PAH).Methods:A retrospective cohort study was conducted. The clinical data of 134 patients with IPF and PAH who underwent lung transplantation at Wuxi People's Hospital Affiliated to Nanjing Medical University from January 2017 to December 2020 were collected. The donor's gender, age, duration of mechanical ventilation, and cold ischemia time, the recipient's gender, age, body mass index (BMI), smoking, history of hypertension and diabetes, preoperative usage of hormones, mean pulmonary arterial pressure (mPAP), cardiac echocardiography and cardiac function, serum creatinine (SCr), N-terminal pro-brain natriuretic peptide (NT-proBNP) as well as surgical type, extracorporeal membrane oxygenation (ECMO) treatment, duration of operation, and plasma and red blood cell infusion ratio were collected. The cumulative survival rates of patients at 30, 60, and 180 days after lung transplantation were calculated by Kaplan-Meier method. The univariate and multivariate Cox proportional hazards regression models were used to analyze the effects of donor, recipient, and surgical factors on early survival in donors after lung transplantation.Results:The majority of donors were male (80.6%). There was 63.4% of the donors older than 35 years old, 80.6% of the donors had mechanical ventilation duration less than 10 days, and the median cold ischemia time was 465.00 (369.25, 556.25) minutes. The recipients were mainly males (83.6%). Most of the patients were younger than 65 years old (70.9%). Most of them had no hypertension (75.4%) or diabetes (67.9%). The median mPAP of recipients was 36 (30, 43) mmHg (1 mmHg≈0.133 kPa). There were 73 patients with single lung transplantation (54.5%), and 61 with double lung transplantation (45.5%). The survival rates of 134 IPF patients with PAH at 30, 60, 180 days after lung transplantation were 81.3%, 76.9%, and 67.4%, respectively. Univariate Cox proportional risk regression analysis showed that recipient preoperative use of hormone [hazard ratio ( HR) = 2.079, 95% confidence interval (95% CI) was 1.048-4.128], mPAP ≥ 35 mmHg ( HR = 2.136, 95% CI was 1.129-4.044), NT-proBNP ≥ 300 ng/L ( HR = 2.411, 95% CI was 1.323-4.392), New York Heart Association (NYHA) cardiac function classification Ⅲ-Ⅳ ( HR = 3.021, 95% CI was 1.652-5.523) were the risk factors of early postoperative death in patients with IPF complicated with PAH (all P < 0.05). In the multivariable Cox proportional risk regression analysis, recipient preoperative hormone usage (model 1: HR = 2.072, 95% CI was 1.044-4.114, P = 0.037; model 2: HR = 2.098, 95% CI was 1.057-4.165, P = 0.034), NT-proBNP ≥ 300 ng/L ( HR = 2.246, 95% CI was 1.225-4.116, P = 0.009) and NYHA cardiac function classification Ⅲ-Ⅳ ( HR = 2.771, 95% CI was 1.495-5.134, P = 0.001) were independent risk factors of early postoperative death in patients with IPF. Conclusions:Preoperative hormone usage, NT-proBNP ≥ 300 ng/L, NYHA cardiac function classification Ⅲ-Ⅳ are independent risk factors for early death in patients with IPF and PAH after lung transplantation. For these patients, attention should be paid to optimize their functional status before operation. Preoperative reduction of receptor hormone usage and improvement of cardiac function can improve the early survival rate of such patients after lung transplantation.