Osteoporosis is a common senile bone metabolism disease， clinically characterized by decreased bone mass， destruction of bone microstructure， increased bone fragility， and easy fracture. It tends to occur in the elderly and postmenopausal women， seriously threatening the quality of life and physical and mental health of the elderly. At present， the treatment of osteoporosis is mainly based on oral western medicines， such as calcium， Vitamin D， and bisphosphonates. Still， there are drawbacks such as a long medication cycle and many adverse reactions. In recent years， due to the advantages of multi-component， multi-pathway， and multi-target， some traditional Chinese medicines and effective ingredients can regulate the osteogenic and osteoclastic differentiation process in both directions and are widely used in the prevention and treatment of osteoporosis. Hippophae rhamnoides is a commonly used herbal medicine， and its fruits are rich in flavonoids， polyphenols， fatty acids， vitamins， and trace elements， which have been proven to have a good anti-osteoporosis effect. Isorhamnetin is the main effective ingredient of Hippophae rhamnoides fruits， which has many pharmacological effects such as anti-inflammation， anti-oxidative stress， anti-aging， and anti-tumor. Studies have shown that isorhamnetin can participate in the regulation of bone metabolism and has a good anti-osteoporosis effect. However， the pharmacological effects and related mechanisms of isorhamnetin against osteoporosis have not been systematically summarized. Therefore， this paper reviewed the pharmacological effects and related mechanisms of isorhamnetin against osteoporosis by referring to relevant literature to provide more basis for the development and application of isorhamnetin.

Improving the nitrogen use efficiency (NUE) of Brassica napus is of significant importance for achieving the national goal of zero growth in chemical fertilizer application and ensuring the green development of the rapeseed industry. This study aims to explore the effects of the nitrate transporter gene BnaNRT1.5s on the nitrogen transport and NUE of B. napus, providing excellent genetic resources for the development of nitrogen-efficient B. napus varieties. The spatiotemporal expression of BnaA05.NRT1.5 as a key nitrogen responsive gene was profiled by qRT-PCR at different growth stages and for different tissue samples of B. napus 'Westar'. Subcellular localization was employed to examine its expression pattern in the cells. Additionally, CRISPR/Cas9 was used to create BnaNRT1.5s knockout lines, which were subjected to hydroponic experiments under high nitrogen (12.0 mmol/L) and low nitrogen (0.3 mmol/L) conditions. After the seedlings were cultivated for 21 days, root and shoot samples were collected for weighing, nitrogen content determination, xylem sap nitrate content assessment, and calculation of total nitrogen and NUE. The B. napus nitrate transporter BnaA05.NRT1.5 was localized to the cell membrane. During the seedling and early bolting stages, BnaA05.NRT1.5 was predominantly expressed in roots, while it was highly expressed in old leaves and mature silique skin during the reproductive stage. Compared with the wild type, the mutant BnaNRT1.5s showed significant increases in the dry weight and total nitrogen of seedlings under both high and low nitrogen conditions. Under low nitrogen conditions, NUE in the roots of BnaNRT1.5s significantly improved. Notably, under both high and low nitrogen conditions, the nitrate content in the shoots of BnaNRT1.5s decreased significantly, while that in the roots increased significantly, resulting in a significantly decreased shoot-to-root nitrate content ratio. BnaNRT1.5s is involved in regulating the transport of nitrate from the roots to the shoots, and its mutation enhances nitrogen absorption and utilization in B. napus seedlings, promoting seedling growth. This study not only provides references for understanding the physiological and molecular mechanisms by which BnaNRT1.5s regulates NUE but also offers valuable genetic resources for improving NUE in B. napus.
Brassica napus/genetics* ; Anion Transport Proteins/metabolism* ; Nitrogen/metabolism* ; Nitrate Transporters ; Plant Proteins/metabolism* ; Nitrates/metabolism* ; Gene Expression Regulation, Plant ; Biological Transport

Myocardial ischemia reperfusion injury(MIRI)has become one of the most serious complications affecting the clinical outcome of patients with cardiovascular diseases.The immune inflammatory response of macrophages is closely related to the occurrence and development of MIRI.Many studies have shown that the NF-κB signaling pathway can participate in MIRI regulation by influencing the polarization and inflammatory state of macrophages,pyrodeath,infiltration and other functions,and is a potential target for MIRI therapy.Therefore,this article will review the research progress of NF-κB signaling pathway between macrophage function and MIRI regulation.

Objective To detect the expression of death-associated protein kinase like 1(DAPL1)and mismatch repair gene(Mut L homologue 1,MLH1)methylation level in bronchoalveolar lavage fluid(BALF)of patients with lung cancer,and further investigate the diagnostic value of gene methylation in early lung cancer and its relationship with clinicopathological features.Methods A total of 142 patients with suspected early stage lung cancer admitted the Second People's Hospital of Mengcheng County from January 2022 to January 2024 were retrospectively selected and divided into lung cancer group(n=82)and lung benign lesion group(n=60)according to the final pathological results.Quantitative real time polymerase chain reaction(qRT-PCR)was used to detect the methylation levels of DAPL1 and MLH1 in BALF samples.The clinical diagnostic value of DAPL1 and MLH1 methylation in early stage lung cancer and its relationship with clinicopathological features of lung cancer patients were analyzed.Results The methylation levels of DAPL1 and MLH1 gene in BALF in lung cancer group were 53.66％(44/82)and 56.10％(46/82),respectively,which were significantly higher than those in benign disease group[11.67％(7/60)and 18.33％(11/60)],and the difference was statistically significant(x2=56.544,20.565,all P＜0.05).The sensitivity of DAPL1 andMLH1 gene methylation in the diagnosis of early lung cancer was 53.66％(44/82)and 56.10％(46/82),the specificity was 88.33％(53/60)and 81.67％(49/60),and the accuracy were 68.31％(97/142)and 66.90％(95/142),respectively.The sensitivity and accuracy of DAPL1 methylation combined with MLH1 methylation in the diagnosis of early lung cancer was 86.59％(71/82),and 85.92％(122/142),respectively,both of which were higher than that of a single index(Z=24.411,16.450,all P＜0.05).The methylation levels of DAPL1 and MLH1 genes in BALF of lung cancer patients were closely correlated with clinical stage,smoking history and lymph node metastasis(x2=5.493,13.083;8.167,6.946;9.303,4.523,all P＜0.05).Spearman correlation showed that DAPL1 and MLH1 gene methylation were positively correlated with clinical stage,smoking history and lymph node metastasis in patients with lung cancer(r=0.523,0.602;0.548,0.498;0.630,0.524,all P＜0.05).Conclusion The methylation of DAPL1 and MLH1 genes in BALF has high clinical diagnostic value for early lung cancer,and the methylation levels of both genes are related to the disease progression and smoking history of lung cancer patients.

OBJECTIVE To improve the diagnosis and treatment level of critically ill infectious diseases， standardize the clinical application of nanopore sequencing and promote the sound development of the technology. METHODS Division of Therapeutic Drug Monitoring of Chinese Pharmacological Society and Expert Committee of Precision Medicine for Clinical Treatment of Guangdong Pharmaceutical Association initiated and organized multidisciplinary experts to discuss and determine the consensus writing outline by using the nominal group method， forming a preliminary consensus draft； expert consultation was performed by using Delphi method， and then experts’ opinions were analyzed and revised to form consensus. RESULTS & CONCLUSIONS Consensuses of Experts on the Application of Nanopore Sequencing Technology in the Detection of Pathogenic Microorganisms covers targeted sequencing， metagenomic sequencing and whole genome sequencing， and is standardized in terms of sample collection and storage， detection process， bioinformatics analysis and report interpretation； the recommendations are provided for the key issues.

With the aging of population, the elderly (≥65 years old) cancer patients have become one of the main populations for cancer care. For inoperable locally advanced head and neck squamous carcinomas, cisplatin-based concurrent chemoradiotherapy is the first-line choice. Several large clinical studies have shown that patients under 70 years of age can still benefit from concurrent chemoradiotherapy, while it should be cautious to apply chemotherapy to patients aged 70-80 years. For elderly patients who are intolerant to cisplatin, carboplatin or other regimens with less gastrointestinal and renal toxicity should be considered. Although anti-epidermal growth factor receptor (EGFR) monoclonal antibodies combined with radiotherapy has been proved to be more effective than radiotherapy alone in total patient population, age-subgroup analysis showed limited benefit in elderly patients. The safety of immune checkpoint inhibitors in elderly patients has been validated and those with high programmed death ligand-1 (PD-L1) expression may benefit from concurrent or neoadjuvant immunotherapy, however, high-level evidence is still lacking. For patients older than 80 years, radiotherapy alone may be superior to concurrent chemoradiotherapy, and hypofractionated radiotherapy for palliative purposes can be safely used in this population.

Radiotherapy is an essential part of comprehensive treatment, as well as a radical treatment for head and neck cancer (HNC). The COVID-19 has continued so far, imposing a great impact on cancer care. Since conventional fractionated radiotherapy (CFRT, 2 Gy/F) requires as long as more than six weeks of treatment time, a huge challenge for epidemic control is created for both hospitals and patients. Hypofractionated radiotherapy (Hypo-RT) may be more suitable than CFRT for patients during pandemic by increasing the fraction size, thus reducing fraction number and treatment duration. Early studies have explored the application of Hypo-RT in HNC in palliative setting, which partially proved its safety and effectiveness. Recently, the efforts have been made in definitive treatment using hypofractionated regimen, as well as its combination with systemic treatment and immunotherapy. Indeed, regarding the pandemic of COVID-19, Hypo-RT has been recommended by several expert consensus in the HNC. In this review, relevant research progress was summarized and clinical implication of Hypo-RT in COVID-19 pandemic era was discussed.

Objective:To observe the clinical characteristics and prognosis of patients with rapidly progressive glomerulonephritis (RPGN) caused by lupus nephritis, antineutrophil cytoplasmic antibodies (ANCA) - associated vasculitis, or primary glomerulonephritis who were treated with peritoneal dialysis (PD) and then withdrew PD because of renal recovery.Methods:Data of the above patients were retrospectively analyzed. The patients were diagnosed as RPGN and received PD therapy in Kidney Disease Center, the First Affiliated Hospital, College of Medicine, Zhejiang University from February 2009 to August 2018. The patients were divided into early withdrawal group (PD time≤183 days, n=24) and late withdrawal group (PD time>183 day, n=24). The differences of clinical characteristics between the two groups were compared. The cumulative incidence of adverse events in both groups was analyzed using Kaplan-Meier curves. Cox proportional hazards model was used to analyze the risk factors influencing the prognosis of patients. Results:Forty-eight RPGN patients were included. The median time of maintaining PD was 178(76, 378) days. Compared with the late withdrawal group, the patients in early withdrawal group had lower levels of urine volume, serum albumin and parathyroid hormone, and lower rates of gross hematuria and hypertension at the beginning of PD, and received higher rates of methylprednisolone impulse, combined immunosuppressive agents, and hemodialysis or continuous renal replacement therapy (all P<0.05). At the time of PD withdrawal, the levels of serum creatinine, serum calcium, serum albumin and parathyroid hormone in the early withdrawal group were significantly lower than those in the late withdrawal group (all P<0.05). The Kaplan-Meier curves showed that there was no significant difference in the cumulative survival of patients in both groups (log-rank test χ2=3.485, P=0.062). Cox regression analysis revealed serum creatinine≥209 μmol/L at the time of PD withdrawal was an independent risk factor for poor prognosis ( HR=5.253, 95% CI 1.757-15.702, P=0.003). Conclusions:PD can be used for RPGN patients caused by lupus nephritis, ANCA-associated vasculitis and primary nephritis. Serum creatinine≥209 μmol/L at the time of PD withdrawal is an independent risk factor for poor prognosis.

Objective: To examine the relative factors of transmural intestinal necrosis(TIN) during multidisciplinary stepwise management facilitating the decision making in patients with acute superior mesenteric vein thrombosis (ASMVT). Methods: Clinical data of patients with ASMVT admitted to Department of General Surgery, Jinling Hospital from January 2009 to June 2017 were reviewed retrospectively. There were 52 males and 37 females, aging (45.9±12.6) years (range: 20 to 69 years). According to the postoperative pathological results and follow-up, the patients were divided into TIN group (n=31) and non-TIN group(n=58, including 18 cases of intestinal stricture). The related factors were compared between ASMVT patients with TIN and patients without TIN by univariate analysis using t test, U test and χ² test accordingly, and factors with statistically significance were subsequently submitted to binary Logistic regression analysis. The predictive value and cut-off point of factors were evaluated by receiver operator characteristic(ROC) curve and area under the curve. Results: In univariate analysis, smoking, hypertension, peritonitis, white blood cell count,haemoglobin, international normalized ratio, blood albumin, thrombosis of superior mesenteric branches vein, free intraperitoneal fluid, decrease of bowel wall enhancement and pneumatosis intestinalis were TIN risk factors (all P<0.05). According to the binary Logistic regression analysis, white blood cell count (OR=1.093, 95%CI: 1.010 to 1.182, P=0.027), thrombosis of the superior mesenteric branches vein (OR=11.519, 95%CI: 1.906 to 69.615, P=0.008), pneumatosis intestinalis (OR=11.140, 95%CI: 2.360 to 52.585, P=0.002) were independent relative factors of TIN in patients with AMI, and the area under the ROC curve of the above factors and predictive model was 0.759 (95%CI: 0.647 to 0.871), 0.745 (95%CI: 0.641 to 0.848), 0.737 (95%CI: 0.621 to 0.854), 0.909 (95%CI: 0.847 to 0.971), respectively. The cutoff value of white blood cell count was 18.1×10⁹/L. Conclusion White blood cell levels, superior mesenteric vein branch thrombosis and pneumatosis intestinalis are independent predictors of TIN in ASMVT.

OBJECTIVE: To study the effect of CYP2D610 (c.100 C>T) on plasma trough concentrations of metoprolol and its metabolite α-hydroxy metoprolol, blood pressure and heart rate in patients with coronary artery disease. METHODS: The patients with coronary artery disease taking metoprolol tablets (=128) and those taking metoprolol sustained-release tablets (=126) were genotyped for CYP2D610 using Taqman real-time quantitative PCR. The trough concentrations of metoprolol and α-hydroxy metoprolol were determined with UPLC-MS/MS, and the dose-normalized concentrations (C/D) were compared among the patients with different CYP2D610 genotypes in both groups. Resting blood pressure and heart rate were recorded in all the patients when the concentration of metoprolol reached the steady state and were compared among the patients with different genotypes. RESULTS: In patients taking metoprolol sustained-release tablets, the plasma trough concentration of α-hydroxy metoprolol was significantly associated with the systolic blood pressure (=0.0204). The CYP2D610 poor metabolizers showed a significant association with the C/D of metoprolol and α-hydroxy metoprolol ( < 0.01) in patients receiving metoprolol in both formulations, and in both groups, the C/D of metoprolol was significantly higher in the patients with a TT genotype than in those with a CC or CT genotype ( < 0.01); compared with those with the CT genotype, the patients with the TT genotype had a significantly lower C/D of α-hydroxy metoprolol ( < 0.01). In patients taking metoprolol sustained-release tablets, those with the CT (=0.0281) and TT (=0.0196) genotypes had lower diastolic blood pressure than patients with the CC genotypes, but the systolic blood pressure or heart rate did not differ significantly among them. CONCLUSIONS CYP2D610T allele mutation can reduce the metabolism of metoprolol, increase the C/D of metoprolol and decrease the C/D of α-metoprolol and diastolic blood pressure in patients with coronary artery disease, but CYP2D610 variation does not significantly affect systolic blood pressure or heart rate in the patients when the concentration of metoprolol reaches a steady state.
Adrenergic beta-Antagonists ; Chromatography, Liquid ; Coronary Artery Disease ; Cytochrome P-450 CYP2D6 ; Genotype ; Humans ; Metoprolol ; Tandem Mass Spectrometry