Objective To explore the changes and comparisons of the four biochemical indicator detection for the early renal im‐pairment in multiple myeloma patients .Methods The 54 patients with multiple myeloma of early onset(MM group) and 54 healthy peoples(control group) were retrospectively analyzed .The levels of serum Cystatin C(Cys C) ,creatinine(Cr) ,β2‐microglobulin(β2‐MG) ,and lactate dehydrogenase(LDH) were detected .And the results for statistical analysis .Results The levels of serum Cys C , Cr ,β2‐MG and LDH were higher significantly in the MM group than in the control group ,the difference was statistically significant (P<0 .05) .In the MM group ,the positive rate of Cys C ,Cr ,β2‐MG ,LDH ,combined detection of Cys C and Cr ,combined detection of β2‐MG and LDH ,combined detection of Cys C ,Cr ,β2‐MG and LDH was 63 .0% ,42 .6% ,74 .1% ,61 .1% ,66 .7% ,85 .2% and 96 .3% respectively .The positive rate of Cys C was higher than Cr ,the difference was statistically significant(P<0 .05) .Between the positive rate of combined detection of β2‐MG ,LDH and Cys C ,Cr ,the difference was statistically significant(P<0 .05) .The positive rate of combined detection of the four biochemical tests was the most highest .Conclusion In the early stage of the renal in‐jury in the patients with MM ,the combined detection of the four biochemical tests is most sensitive to discovery the early stage of the renal glomerular function injury .

OBJECTIVE ToobservetheprotectiveeffectandmechanismofCompoundGinkgo biloba(CGB)againstalcohol-inducedliverinjury.METHODS MiceweregivenCGB0.125,0.25and 0.75 g·kg -1 ,Ginkgo biloba extract (GBE)0.1 25 g·kg -1 and bifendate(Bif)0.1 5 g·kg -1 for 8 weeks, respectively.At the end of 4th week the mice were given wine by gavage (56% V/V,0.01 L·kg -1 ), and (56% V/V,0.016 L·kg -1 )at the end of the 8th week.The serum was obtained to measure alanine transaminase (GPT),aspartate aminotransaminase (GOT),mitochondrial aspartate aminotransferase (mGOT)and tumor necrosis factor-α(TNF-α).Liver histopathology was revealed by HE staining.The protein expression of cytochrome P450 (CYP)2E1 ,NF-E2-related factor 2 (Nrf2)and TNF-αin the liverwasanalyzedbyWesternblotting.RESULTS Comparedwithnormalcontrolgroup,theactivitiesof GOT and mGOT were increased in model group (P<0.01 ).Compared with model group,CGB 0.25 and 0.75 g·kg -1 groups and Bif 0.1 5 g·kg -1 group significantly decreased the activity of GOT and mGOT in serum (P<0.05,P<0.01 ),while there was no significant difference between these groups in serum GPT activity (P>0.05).Fatty degeneration and neutrophil infiltration were significantly ameliora-ted in CGB 0.25 and 0.75 g·kg -1 groups.Preliminary mechanism research showed CGB not only increased the protein expression of Nrf2 with a positive dose-effect relationship (r=0.942,P<0.01 ), but reduced the protein expression of hepatic CYP2 E1 and the level of TNF-αin hepatic tissue with a negative dose-effect relationship (r=-0.987,P<0.05;r=-0.940,P<0.05).In addition.The level ofTNF-αwasalsosignificantlydecreasedintheserum(P<0.05,P<0.01).CONCLUSION CGB may protect the liver fro m acute alcoholic injury and the mechanis m may be that it increases the protein expression of Nrf2,restrains the protein expression of hepatic CYP2E1 and TNF-αand reduces the TNF-αlevel in the serum.

The paper is to report the pharmacokinetics of furosemide in rats living at plain area and high altitude. After intragastric administration of furosemide (2.87 mg x kg(-1)), serial blood samples (0.5 mL) were collected by retro-orbital puncture at 0, 20 min, 40 min, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 h, samples were determined by LC-MS/MS, and plasma concentration-time data were analyzed by DAS 2.0 software to get the related pharmacokinetic parameters. The main pharmacokinetic parameters: area under curve (AUC), mean residence time (MRT), the biological half-life (t1/2) and the peak concentration (C(max)) of furosemide, were significantly increased at high altitude, the time to reach peak concentration (t(max)) and clearance (CL) was significantly decreased. This study found significant changes on the pharmacokinetics of furosemide under the special environment of high altitude. This finding may provide some references for clinical rational application of furosemide at high altitude.

Objective:To study the pharmacokinetics of propranolol in Wistar rats after acute exposure to high altitude.
Methods:Fourteen male Wistar rats (200±20) g were selected. After administration of propranolol tablets (0.05 g/kg, i.g.), blood samples (3 mL) were collected at 0, 20, 40 min,1, 1.5, 2, 4, 6, 8, 12 and 24 h, respectively. The pharmacokinetic parameters were determined by LC-MS/MS and DAS 2.0 software.
Results:The main pharmacokinetic area under concentration-time curve (AUC), mean retention time (MRT), half-life (t1/2) and peak plasma concentration (Cmax) of propranolol were increased by 442.61%, 47.45%, 73.13%and 352.97%, respectively, whereas Tmax and clearance (CL) were decreased by 80.87%and 68.94%, respectively.
Conclusion:This study displays significant changes in the pharmacokinetics of propranolol under high altitude, which may provide evidence for clinical rational application of propranolol at high altitude.

Passive leg raising is widely used in clinic, but it lacks of specialized mechanical raise equipment. It requires medical staff to raise leg by hand or requires a multi-functional bed to raise leg, which takes time and effort. Therefore we have developed a new medical electric leg-raising machine. The equipment has the following characteristics: simple structure, stable performance, easy operation, fast and effective, safe and comfortable. The height range of the lifter is 50-120 cm, the range of the angle of raising leg is 10°-80°, the maximum supporting weight is 40 kg. Because of raising the height of the lower limbs and making precise angle, this equipment can completely replace the traditional manner of lifting leg by hand with multi-functional bed to lift patients' leg and can reduce the physical exhaustion and time consumption of medical staff. It can change the settings at any time to meet the needs of the patient;can be applied to the testing of PLR and dynamically assessing the hemodynamics; can prevent deep vein thrombosis and some related complications of staying in bed; and the machine is easy to be cleaned and disinfected, which can effectively avoid hospital acquired infection and cross infection; and can also be applied to emergency rescue of various disasters and emergencies.

Objective:To observe the clinical effect of arthrocentesis combined with liquid phase con-centrated growth factor(CGF)injection in the treatment of unilateral temporomandibular joint osteoarthri-tis(TMJOA),in order to provide a new treatment option for TMJOA patients.Methods:In this non-randomized controlled study,patients diagnosed with unilateral TMJOA who visited the center for tem-poromandibular joint disorder and orofacial pain of Peking University School and Hospital of Stomatology from June 2021 to January 2023 were selected as research objects.The patients were divided into experi-mental group and control group,which were selected by patients themselves.The experimental group re-ceived arthrocentesis combined with liquid phase CGF injection and the control group received arthrocen-tesis combined with HA injection.Both groups were treated 3 times,once every two weeks.The clinical effect was evaluated by the maximum mouth opening,pain value and the degree of mandibular function limitation 6 months after treatment.The change of condylar bone was evaluated by cone beam CT(CBCT)image fusion technology before and after treatment.Results:A total of 20 patients were included in the experimental group,including 3 males and 17 females,with an average age of(34.40± 8.41)years.A total of 15 patients were included in the control group,including 1 male and 14 females,with an average age of(32.20±12.00)years.There was no statistical difference in general information between the two groups(P＞0.05).There were no statistical differences in the mouth opening,pain value and the degree of jaw function limitation between the two groups before treatment(P＞0.05),and all of them improved 6 months after treatment compared with before treatment(P＜0.05).However,the mouth opening of experimental group was significantly higher than that of control group 6 months after treatment(P＜0.05),and the degree of jaw function limitation was significantly lower than that of con-trol group(P＜0.05).CBCT 2D images showed that the condylar bone of both groups was smoother after treatment than before treatment,and image fusion results showed that 10 patients(50.0％)in the experimental group and 5 patients(33.3％)in the control group had reparative remodeling area of con-dylar bone,and there was no statistical difference between them(P＞0.05).Except for one CGF pa-tient,the other patients in both groups had some absorption areas of condylar bone.Conclusion:The ar-throcentesis combined with liquid phase CGF injection can improve the clinical symptoms and signs of unilateral TMJOA patients in short term,and is better than HA in increasing mouth opening and impro-ving jaw function.CBCT fusion images of both patient groups show some cases of condylar bone repara-tive remodeling and its relevance to treatment plans still requires further study.

OBJECTIVETo investigate the influence of a sudden increase of altitudes (within 2500 m) in winter on cardiomyocyte functions in rats.

METHODSThirty male Wistar rats were randomly divided into groups A (55 m), B (1520 m), and C (2260 m) and subjected to simulated conditions at the indicated altitudes in winter for 3 days. Blood gas analysis, venous blood biochemistry, and measurements of SOD activity and myocardial concentrations of MDA and NO were performed. Histopathological changes in the left ventricle were observed with HE staining and electron microscopy.

RESULTSBlood pH and PCO2 did not differ significantly between the 3 groups, but PO2 and BE in groups B and C decreased significantly compared with those in group A (P<0.01). Compared with group A, the rats in group C showed obviously increased myocardial enzymes, MYB, Tn-I, and MDA contents (P<0.01) with significantly decreased SOD activity (P<0.05); both groups B and C showed significantly decreased NO content in the myocardium (P<0.01). Histopathologically, the myocardial fiber in group C showed irregular alignment, disruption, and mitochondrial expansion.

CONCLUSIONA sudden increase of altitude to 2260 m in winter can potentially cause hypoxic cardiomyocyte damage as a result of oxidative and environmental stresses.

Altitude ; Animals ; Hypoxia ; pathology ; Male ; Malondialdehyde ; metabolism ; Myocardium ; metabolism ; pathology ; Nitric Oxide ; metabolism ; Oxidative Stress ; Rats ; Rats, Wistar ; Superoxide Dismutase ; metabolism

OBJECTIVETo study the pharmacokinetics of propranolol and metoprolol in rats after acute exposure to high altitude.

METHODSWistar rats were randomly assigned into 4 groups for treatment with intragastric administration of propranolol or metoprolol after acute exposure to high altitude (4010 m) or normal altitude (50 m). Venous blood samples were collected from the rats at different time points after drug administration to determine the drug concentrations in the plasma and plasma ultrafiltrate using liquid chromatography-mass spectrometry (LC-MS/MS).

RESULTSThe protein binding rate of propranolol was significantly increased but that of metoprolol remained unchanged after acute exposure to high altitude. Compared with the rats exposed to normal altitude, the rats with acute exposure to high altitude showed significant alterations in the pharmacokinetic parameters of the drugs, shown by increased Cmax and AUC, prolonged t1/2 and MRT, and lowered Clz/F of propranolol, and by increased Tmax and prolonged t1/2 and MRT of metoprolol without obvious changes of the parameters of the compartmental model.

CONCLUSIONSignificant changes in the pharmacokinetics of propranolol and metoprolol occur in rats after acute exposure to high altitude possibly in relation to, apart from the changes in plasma protein binding ratio and blood gas, alterations in metabolic enzyme activities, increased blood viscosity, and species and general conditions of the animals.

Altitude ; Animals ; Chromatography, Liquid ; Metoprolol ; pharmacokinetics ; Propranolol ; pharmacokinetics ; Protein Binding ; Rats ; Rats, Wistar ; Tandem Mass Spectrometry

OBJECTIVETo investigate the changes in hepatic functions and activities of CYP1A2 and CYP3A4 in rats after acute exposure to high altitude.

METHODSTwelve healthy male Wistar rats were randomly divided into control group and exposure group for acute exposure to normal and high altitude (4010 m) environment. Blood samples were collected from the vena orbitalis posterior for detection of the hepatic function. Hepatic pathologies of the rats were examined microscopically with HE staining. Liver microsomes were extracted by differential centrifugation to assess the activities of CYP1A2 and 3A4 using P450-GloTM kit.

RESULTSIn rats with acute exposure to high altitude, AST, ALT, and ALP all increased significantly by 48.50%, 47.90%, and 103.02%, respectively, and TP decreased significantly by 17.80% as compared with those in rats maintained in normal altitude environment (P<0.05). Pathological examination of the liver revealed edema of the central vein of the liver and hepatocyte karyopyknosis in rats after acute exposure to high altitude, which also resulted in significantly lowered activities of CYP1A2 and 3A4 in the liver (by 96.56% and 43.53%, respectively).

CONCLUSIONAcute exposure to high altitude can cause obvious liver injuries and lowered activities of CYP1A2 and 3A4 in rats to severely affect drug metabolism in the liver and result in increased concentration, prolonged half-life and reduced clearance of drugs.

Altitude ; Animals ; Cytochrome P-450 CYP1A2 ; Cytochrome P-450 CYP3A ; metabolism ; Cytochromes ; metabolism ; Liver ; pathology ; Male ; Microsomes, Liver ; enzymology ; Rats ; Rats, Wistar

LncRNA H19 encoded by the H19 imprinting gene plays an important regulatory role in the cell. Recently study has found that in hypoxic cells, the expression of H19 gene changes, and the transcription factors and protein involved in the expression change accordingly. Through the involvement of specific protein 1 (SP1), hypoxia-inducible factor-1α (HIF-1α) binds directly to the H19 promoter and induces the up-regulation of H19 expression under hypoxic conditions. The tumor suppressor protein p53 may also mediate the expression of the H19 gene, in part by interfering with HIF-la activity under hypoxia stress. The miR675-5p encoded by exon 1 of H19 promotes hypoxia response by driving the nuclear accumulation of HIF-1α and reducing the expression of VHL gene, which is a physiological HIF-1α inhibitor. In addition, under the condition of hypoxia, the expression of transporter on cell membrane changes, and the transition of the intracellular glucose metabolism pathway from aerobic oxidation to anaerobic glycolysis is also involved in the involvement of H19. Therefore, H19 may be a key gene that maintains intracellular balance under hypoxic conditions and drives adaptive cell survival under conditions of hypoxia stress.
Cell Hypoxia ; genetics ; Genes, Tumor Suppressor ; physiology ; Humans ; Hypoxia-Inducible Factor 1, alpha Subunit ; genetics ; RNA, Long Noncoding ; Up-Regulation ; physiology ; Von Hippel-Lindau Tumor Suppressor Protein ; genetics