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

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.

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.

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.

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 investigate the risk factors,mechanism and treatment strategies of expanding regional brain injury (traumatic intracerebral contusion or hematoma) in patients with acute traumatic epidural hematoma (ATEDH) after surgical evacuation.Methods Fifty-nine patients with ATEDH,admired to and accepted surgical evacuation in our hospital from February 2013 to September 2018,were chosen in this study;their clinical data and CT imaging data were retrospectively analyzed.The volume ofintracranial hematoma was measured by 3D Slicer software.According to the progress of local brain injury revealed by first CT examination after surgical evacuation,patients with ATEDH were divided into progressive group and non-progressive group.Risk factors of patients with expanding regional brain injury after surgery were analyzed by univariate and multivariate Logistic regression analyses.Results After surgery,22 showed expanding regional brain injury,accounting for 37.29％:9 occurred expanding intracerebral hematoma,and 2 of them died after conservative treatment;two had both expanding intracerebral contusion and hematoma;11 expanding intracerebral contusion patients developed into hematoma,and three of them occurred delayed intracerebral hematoma adjacent to the area of ATEDH,and two underwent secondary craniotomy with good recovery.As compared with patients from the non-progressive group,progressive group had significantly higher percentages of patients with preoperative hyperglycemia (＞9.1 mmol/L),patients with preoperative abnormal coagulation and patients accepted decompressive craniectomy (P＜0.05).Multivariate Logistic regression analysis revealed that preoperative abnormal coagulation was an independent risk factor for expanding intracerebral contusion or hematoma after surgery (OR=6.498,95％CI:1.076-39.253,P=0.041).Conclusion Expanding regional brain injury has high morbidity in patients with ATEDH after surgery evacuation;preoperative abnormal coagulation is an independent risk factor for its occurrence.

Objective To explore the risk factors,mechanism and treatment strategies of secondary brain injury (cerebral hemorrhage or cerebral infarction/encephaledema) adjacent to acute epidural hematoma after surgical evacuation.Methods Forty-four patients with acute epidural hematoma underwent craniotomy in our hospital from March 2013 to December 2018 were chosen in this study.According to postoperative CT or MR imaging examination results,patients were divided into group of secondary brain injury (n=11) and group of non-secondary brain injury (n=33).The clinical data of the two groups were compared,and the significance of epidural hematoma thickness in assessing secondary brain injury was analyzed by receiver operating characteristic (ROC) curve.Binary Logistic regression analysis was used to analyze the independent risk factors affecting secondary brain injury.Results After surgery,11 showed secondary brain injury:3 occurred cerebral hemorrhage,one of whom was diagnosed as having cerebral venous hemorrhage in the cortical vein drainage area caused by traumatic cerebral venous circulation disorder;6 had cerebral infarction/encephaledema,and 2 occurred hemorrhagic cerebral infarction/encephaledema;two underwent secondary craniotomy and both achieved satisfactory effect.As compared with patients from the non-secondary brain injury group,patients fromsecondary brain injury group had significantly higher percentage of patients with epidural hematoma thickness ≥ 33.5 mm (P＜0.05).ROC curve analysis showed that the thickness of epidural hematoma had predictive value in secondary brain injury after surgery (P＜0.05),and area under the curve was 0.722 and diagnostic threshold was 33.5 mm.Binary Logistic regression analysis revealed that epidural hematoma thickness ≥33.5 mm was an independent risk factor for secondary brain injury adjacent to epidural hematoma after surgery (odds ratio=7.367,P=0.024,95％CI=1.298-41.797).Conclusions Acuteepidural hematoma thickness ≥33.5 mm is a high-risk factor associated with secondary brain injury adjacent to epidural hematoma after surgery.Intracranial venous circulatory disorders have non-negligible effect on occurrence of secondary brain injury.