[ABSTRACT]AIM:Toexploretheeffectoftheelasticmodulusandsizesofliquidcrystal(LC)phasesonosteo-genic differentiation based on OPC/PU composite substrate by mimicking the microenvironment in rat bone mesenchymal stem cells (rBMSCs).METHODS: A series of composite substrates with different elastic modulus were constructed via modulation of LC content in the composites .The surface phase structure was observed by polarized microscopy , and the mechanical property was measured by a universal material testing machine .Furthermore, the laser confocal microscope was employed to observe the spreading , polarization and the cytoskeleton arrangement of the rBMSCs .The proliferation of rBM-SCs was evaluated by CCK-8 assay.The specific mRNA expression of osteogenic differentiation such as collagen Ⅰ, and osteopontin on the composite membranes was detected by real-time PCR.RESULTS:The size and number of LC phase in-creased and the elastic modulus of the composite substrates decreased with the increase of the LC content .The rBMSCs ex-hibited better characteristics of initial adhesion , spreading and proliferation on the OPC 10-PU and OPC30-PU in the early and medium culturing .The rBMSCs displayed higher expression of collagen Ⅰ and osteopontin on the OPC10-PU in the early and medium osteogenic induction , while the high expression of these osteogenic genes occured on the OPC 30-PU and OPC50-PU in later osteogenic induction .The emphasis of genetic expression was switched from collagen Ⅰin the early and medium osteogenic induction to osteopontin in the later stage .CONCLUSION:When the content of LC remained low in the composite substrates , rBMSCs mainly responded to the mechanical stimuli induced by substrate stiffness and exhibited distinguished cellular behaviors;with the increase in the LC content , rBMSCs had strong interactions with LC by sensing the viscoelasticity of LC , probably resulted from the contribution of both substrate stiffness and the viscoelasticity of LC phase .

Objective： ：To detect the gene mutation in cholangiocarcinoma patients using the next generation sequencing (NGS) technology, and to analyze its correlation to the prognosis of the patients. Methods: From June 2016 to June 2018, 40 patients diagnosed with cholangiocarcinoma received NGS examination to screen the possible mutations (single base mutation, structural variation, copy number variation and gene fusion, etc.). The disease control rates (DCR), progression-free survival (PFS) and overall survival (OS) of the patients, who received the first line therapy, were retrospectively reviewed to analyze the relationship between signaling pathway as well as its genetic variation and the prognosis of cholangiocarcinoma patients. Results: The median PFS of patients with and without TP53 mutation was 11.0 and 8.3 months, respectively (P=0.332), while OS was 14.3 and 32.9 months, respectively (P=0.041). The median PFS of patients with and without PI3K mutations was 8.3 and 11.0 months, respectively (P=0.285), while OS was 14.3 and 37.0 months, respectively (P=0.020). The median PFS of patients with and without mTOR pathway mutations was 6.3 and 10.3 months, respectively (P=0.020), while OS was 15.6 and 19.6 months, respectively (P=0.892). There was no significant effect of pathway-related gene mutations on patients’survival. Conclusion: The prognosis of cholangiocarcinoma patients with TP53 and PI3K pathway activation had obviously poor prognosis than those without. No significant difference was observed between the patients with and without mTOR pathway activation and IDH mutation.

Objective To study the protective effect of shenfu injection on cerebral ischemia reperfusion injury in rats.Methods 120 male Sprague Dawley (SD) rats(320-350 g) were randomly divided into sham operation group,model control group,Nimodipine injection group,low,medium and high dose group of shenfu injection according to gender weight.20 males in each group were given medicine once a day for 7 days before operation.The cerebral ischemia model was established by thread embolization after 5 days of administration.In the sham operation group,the other operations were the same as those in the model group except for carotid artery ligation and thread insertion.After 24 hours of perfusion,the neurological score,abdominal aorta blood flow,malondialdehyde (MDA),superoxide dismutase (SOD) and glutathione (GHS) levels in brain tissues were measured.Triphenyltetrazolium chloride (TTC) staining was used to calculate the area of cerebral infarction and pathological examination of brain tissues.Results Compared with the model control group,the middle and high dosage of shenfu injection could obviously improve the nerve function and increase the percentage of cerebral infarction area (P ＜ 0.05);the high dosage group of shenfu injection could obviously decrease the whole blood viscosity (P ＜ 0.01);the middle and high dosage of shenfu injection could obviously reduce the level of MDA in rat brain tissue (P ＜ 0.01) while increasing the levels of SOD and GSH (P ＜0.01),finally could significantly improve the pathological changes of brain tissues such as mild swelling of nerve fibers,mild neuronal degeneration,inflammatory interstitial edema and inflammation.Conclusions Shenfu injection has obvious protective effect on cerebral ischemia reperfusion model in rats.

Objective To investigate the clinical features and treatment of chronic invasive fungal rhinosinusitis(CIFRS).Methods From June 2006 to August 2011,seven patients were pathologically diagnosed as CIFRS in otorhinolaryngology department of Peking university first hospital and included in this study.The clinical records were reviewed.The clinical features,clinical course,symptoms,clinical signs,CT/MRI scan of the sinuses,surgical approach,postoperative pathology and medications were analyzed retrospectively.These 7 patients received both surgical and systemic anti-fungal treatment.Among them,2 cases with characteristically clinical features were addressed into further analyses to explore the clinical feature and treatment of CIFRS.Results Among the 7 patients,5 were female and 2 were male.The course of diseases were from 2 months to 8 years.All patients had no systemic immune diseases and history of diabetes mellitus,while 1 case had a history of facial trauma,and another 1 case had received antibiotics for long-stay in bed after a car accident.The onset lesions of 6 cases were in unilateral maxillary sinus and 1 in unilateral ethmoid sinus.Aspergillus fungi were detected in 6 cases and mold fungi were detected in 1 case by pathology or fungal culture.After follow-up for 1-5 years,6 patients were cured,and 1 was died.Conclusions CIFRS are often diagnosed in patients with normal immune function.Lesions alwasys occur in single sinus,and maxillary sinus is the most commonly involved.Aspergillus is the most common pathogens.Early clinical manifestation and sinus CT images are lack of specificity.Surgery associated with adequate antifungal treatment might be the best treatment strategy.

BACKGROUND:With the variation of disease treatment modes and the in-depth research on senile osteoporosis in recent years,increasing studies have confirmed that traditional Chinese medicine has a significant effect on the prevention and treatment of senile osteoporosis. OBJECTIVE:To investigate the effect of Yishen Gushu Formula on bone metabolic markers in patients with osteoporosis of kidney deficiency and blood stasis type. METHODS:102 patients with senile osteoporosis of kidney deficiency and blood stasis type who were treated at Ruikang Hospital Affiliated to Guangxi University of Traditional Chinese Medicine from July 2020 to March 2022 were enrolled,including 32 males and 70 females,aged 71-93 years.All patients were randomly divided into two groups,with 51 patients in each group.The control group was treated with calcium carbonate D3 granules and sodium alendronate tablets,while the treatment group was treated with Yishen Gushu Formula beyond the control group.Treatments in each group lasted 3 months.Bone mineral density of the L1-4 lumbar vertebrae and left femoral neck,visual analog scale score,and serum levels of osteocalcin,osteopontin,type Ⅰ collagen cross-linked C-terminal peptide and tartrate resistant acid phosphatase were measured before and 3 months after treatment.Traditional Chinese medicine syndrome score and therapeutic efficiency were also assessed. RESULTS AND CONCLUSION:After 3 months of treatment,the bone mineral density of the lumbar vertebrae(L1-4)and left femoral neck was significantly increased in both two groups(P<0.05),and the bone mineral density of the lumbar vertebrae(L1-4)and left femoral neck was significantly higher in the treatment group than the control group(P<0.05).The visual analog scale scores of both groups after 3 months of treatment were lower than those before treatment(P<0.05),and the visual analog scores of the treatment group after 3 months of treatment were lower than those of the control group(P<0.05).After 3 months of treatment,the serum levels of osteocalcin,osteopontin,type Ⅰ collagen cross-linked C-terminal peptide and tartrate resistant acid phosphatase were significantly improved in both two groups,while compared with the control group,the serum levels of osteocalcin and osteopontin were significantly higher(P<0.05)and the serum levels of type Ⅰ collagen cross-linked C-terminal peptide and tartrate resistant acid phosphatase were significantly lower in the treatment group(P<0.05).After 3 months of treatment,the Traditional Chinese medicine syndrome scores were decreased in both two groups,while the Traditional Chinese medicine syndrome scores in the treatment group were lower than those in the control group.After 3 months of treatment,no significant adverse reactions occurred in both groups.The total effective rate was 88.2%and 70.6%in the treatment and control groups respectively,and there was a significant difference between the two groups(P<0.05).To conclude,Yishen Gushu Formula combined with anti-osteoporosis drugs can significantly improve the clinical symptoms of patients with senile osteoporosis of kidney deficiency and blood stasis type and prevent disease progression by regulating bone metabolism,increasing bone mineral density,and relieving pain.

Objective To evaluate the treatment outcome advanced hypopharyngeal carcinoma by surgery with laryngeal function preservation.Methods Twenty cases with squamous cell carcinoma of the hypopharynx who were treated by the function preserved surgery between January 2000 and March 2012 were reviewed.Of the patients 19 were males and 1 female,and their median age was 62.0 years.Eight cases were only applied with total or subtotal hypopharyngectomy,and others received total or subtotal hypopharyngectomy with partial-laryngectomy.Postoperative functional training was performed.Radiotherapy was used in all cases from 2 to 4 weeks after surgery.Results Speech intelligibility remained in all 20 patients and 80.0％ of the patients were extracted the trachea tube in the average 60 days.Conclusions Laryngeal functions of larynx can be preserved in advanced hypopharyngeal carcinoma by total or subtotal hypopharyngectomy alone or plus partial laryngectomy with functional reconstruction,and the patients can maintain their rational speech and swallowing functions.

BACKGROUND:Some studies have found that ferroptosis of osteoblasts can be an important mechanism to induce the occurrence and development of hormone-induced femoral head necrosis.With the development of Chinese medicine,some scholars have found that some Chinese medicine monomer,Chinese medicine compound and Chinese patent medicine can regulate the ferroptosis of osteoblasts through various pathway mechanisms,and finally play a role in the treatment of steroid-induced avascular necrosis of femoral head. OBJECTIVE:To investigate the relationship between ferroptosis and steroid-induced avascular necrosis of femoral head and the mechanism of Chinese medicine regulating ferroptosis of osteoblasts in the treatment of steroid-induced avascular necrosis of femoral head,so as to provide new ideas for the diagnosis and treatment of steroid-induced avascular necrosis of femoral head. METHODS:With"ferroptosis,steroid-induced avascular necrosis of femoral head,osteoblast,Chinese herbal medicine,glucocorticoid,iron metabolism,reactive oxygen species,glutathione peroxidase"as Chinese search terms,and"ferroptosis,hormonal necrosis of the femoral head,osteoblast,Chinese herbal medicine,glucocorticoid,iron metabolism,ROS,GPX4"as English search terms,the search was conducted on CNKI,PubMed,WanFang,VIP and other databases.The relevant articles on osteoblast ferroptosis and steroid-induced avascular necrosis of femoral head and the regulation of Chinese herbal medicine intervention from the establishment of each database to 2023 were screened.Finally,76 articles were systematically analyzed. RESULTS AND CONCLUSION:(1)Ferroptosis of osteoblasts plays an important role in the pathogenesis of steroid-induced avascular necrosis of femoral head.(2)The occurrence of ferroptosis in osteoblasts is regulated by a variety of mechanisms,such as intracellular iron overload causing ferroptosis.Lipid peroxidation damages cell membrane and causes ferroptosis.Cystine/glutamate reverse transporter induced ferroptosis by influencing glutathione level and glutathione peroxidase 4 activity.Fenton reaction in the cell produces a large number of reactive oxygen species and causes ferroptosis.(3)Chinese medicine monomer icariin,Chinese medicine compound Qinge pills and Chinese patent medicine Bushen Huoxue granules can regulate the occurrence of osteoblast ferroptosis,and help to prevent and treat steroid-induced avascular necrosis of femoral head.(4)The mechanism of ferroptosis in osteoblasts is still unclear.Further investigation on the mechanism of action of both is expected to provide a new choice for clinical treatment of steroid-induced avascular necrosis of femoral head.

To study the protective effect of Xingnaojing Injection on early global brain ischemia-induced deep coma in rats.
 Methods: The deep coma model was induced by global brain ischemia by using four-vessel occlusion method in male SD rats. According to the body weight, the rats were randomly divided into 8 groups: a model control group, three different dose of Xingnaojing Injection (1.8, 3.6 and 5.4 mL.kg-1) groups, a Xingnaojing Injection (3.6 mL.kg-1) plus PI3K inhibitor group, a naloxone injection (0.04 mL.kg-1) group and a naloxone injection (0.04 mL.kg-1) plus Xingnaojing Injection (3.6 mL.kg-1) group (n=8 per group). In addition, eight animals served as the sham group were performed same operation with the model group excepting no blockage of the blood vessels. After the operation, three different doses of Xingnaojing Injection and/or naloxone injection were given intravenously once a day for three days. Ten μL PI3K inhibitor (LY294002, 10 mmol/L) was injected via anterior cerebral ventricle at once after global brain ischemia. The awakening time after the first drug treatment, the grasping power and the autonomous activity within 10 min after the last drug treatment were recorded. The levels of both dopamine (DA) and glutamate (Glu) in cerebrospinal fluid were detected by ELISA. The pathological changes were observed in brain tissue slices with HE staining and the protein levels of Akt/p-Akt and cAMP-response element binding protein (CREB)/p-CREB in hippocampus were detected by Western blotting.
 Results: Comparing with the model group, single administration of Xingnaojing Injection could significantly shorten the waking time (P<0.05) and continuous administration of Xingnaojing Injection for 3 d could increase grasping power, distance, frequency and duration of autonomous activities (P<0.05 or P<0.01) in the deep coma rat. Also, Xingnaojing Injection could inhibit these increases in neurotransmitters DA and Glu contents (P<0.05 or P<0.01), and improve pathological changes of hippocampal tissue. Xingnaojing Injection significantly induced protein phosphorylation of both Akt and CREB (P<0.05 or P<0.01); this effect was inhibited by PI3K inhibitor (P<0.05 or P<0.01). Moreover, the protective effects of naloxone on awakening time, grasping power, the autonomous activity and hippocampus damage in global brain ischemia-induced deep coma could be enhanced by joint use of Xingnaojing Injection (P<0.05 or P<0.01).
 Conclusion: Xingnaojing Injection could significantly improve deep coma induced by global brain ischemia in rat, which is related to inducing PI3K/Akt-dependent protein phosphorylation of CREB, and reducing hippocampal damage. The protective effect of Xingnaojing Injection is synergistically enhanced by naloxone.
Animals ; Brain ; Brain Ischemia ; Coma ; Drugs, Chinese Herbal ; Male ; Phosphatidylinositol 3-Kinases ; Rats ; Rats, Sprague-Dawley

Adipocytokines are polypeptides or proteins that are secreted by fat cells with a wide range of biological activities. Adiponectin is a fatty cytokine with insulin sensitization. It possesses the function of anti- diabetes, atherosclerosis and anti-inflammation. Adiponectin may participate in regulating the development of cognitive impairment, which is considered as a new regulatory factor for cognitive impairment.
Adiponectin ; Cognitive Dysfunction ; Diabetes Mellitus ; Humans ; Insulin ; Insulin Resistance