OBJECTIVE:To establish a simple individualized dosage regimen of multiple oral dosing of Theophyllin. METHODS:Based on pharmacokinetic parameters,Excel function was used to design the dosage regimen of multiple oral dosing extravascular administration of one-compartment model with Theophylline as an example. RESULTS:The following parameters such as plasma drug concentration at any time (t) since administration of Theophylline,peak time,maximum steady plasma-drug concentration,minimum steady plasma-drug concentration,accumulation coefficient,fluctuation percentage,fluctuation amplitude,and dosage for children and the old could be obtained and the concentration-time curves were able to be drawn from the input data including physical and pathological parameters,dosage (X0) of Theophylline,interval ?,absorption rate constant (Ka),drug clearance rate (CL),absorption fraction (F) and apparent volume of distribution (Vd). CONCLUSION:The method adopted in our study is simple,reliable and intuitive,and it is applicable for the design of the individualized dosage regimen of Theophyllin.

Objective To assess the outcome of de-epithelialied ileocystoplasty combined with strengthened pelvic floor in patients with neurogenic bladder.Methods Twelve patients (9 male,3 female) aged from 18 -27 years (averaged 25 years) with neurogenic bladder received de-mucosalized seromuscular ileocystoplasty combined with strengthened pelvic floor,and were evaluated by urodynamic parmeters,upper urinary tract image appearance,and serum creatinine before and one year after operation.Results After operation,the max cystometric capacity (412 ± 32 ml),bladder compliance (26.2 ± 4.0ml/H2O),relative safety cystometric capacity (368 ±26 ml) and max flow rate (20 ±3 ml/s) were respectively significantly higher than those preoperation(247 ±27 ml,4.4 ± 1.2 ml/cm H2O,206 ±24 ml,11 ±2ml/s,P ＜ 0.05).Moreover,the post voided residual (26 ± 8 ml) and detmsor leakage point pressure (17.8 ±3.6 cm H2O) were significantly lower than those of preoperation (136 ± 25 ml,63.1 ± 4.9cm H2O,P ＜0.05).The vesicoureteral reflux disappeared in five (63％) cases,and was relieved in the remaining three cases.Of the five cases with renal insufficiency,three (60％) cases had normal serum creatinine level,none had increased serum creatinine levels.After operation,late healing occurred in two ( 17％ ) cases,intestinal obstruction in one (8％),vesicoabdominal fistula in one (8％),and no cases had mucous urine.Clean intermittent self-catheterization was performed in one case (8％) to empty the bladder due to a fever resulting from urinary tract infection,the remaining 12 (92％) cases could empty their bladders through abdominal pressure.Conclusions De-mucosalized seromuscular ileocystoplasty combined with strengthened pelvic floor results in a good outcome for the patients with neurogenic bladder.

Epimutations are errors in the normal process of epigenetic regulation which can result in aberrant transcriptional silencing of a normally active gene or reactivation of a normally silent gene.Epimutations are generally considered to be somatic events and to be confined in affected tissues.However, recent studies of patients with hereditary nonpolyposis colorectal cancer(HNPCC) have showed that allele-specific hypermethylation of CpG islands in the promoter region of the MLH1 gene, one of the causes of the tumor,existed in all the tissues examined.In addition,germ-line epimutations of other tumor suppressor genes(TSGs),such as MSH2 and BRCA1,have also been reported,demonstrating that epimutations might arise in the germline(during gametogenesis or early embryonic development).The role of germ-line epimutations might be as important as germ-line mutations in human disease.We reviewed the update on germ-line epimutations of TSGs including the possible mechanisms underlying germ-line epimutations,the possibility of transgenerational inheritance.and their impact on our understanding of human disease.

OBJECTIVEThe experiment was conducted to study the effect of soaking seeds with biogas slurry on seed germination and growth of Tagetes erecta so that we can provide theory base for cultivation management of T. ercta.

METHODIn order to find the best combine of biogas slurry concentration (25%, 50%, 75%, 100%) and soaking time (2, 3, 4, 5 h), completely randomized design was selected, germination percentage, seedling height, root length, root activity, content of chlorophyll (a, b) and MDA were analyzed and principle component analysis was adopted.

RESULTBoth soaking for 5 h in 25% biogas slurry and soaking for 4 h in 50% biogas slurry had the highest germination percentage (81.3%). Soaking for 5 h in 50% biogas slurry had the longest root, and soaking for 4 h in 50% biogas slurry had the highest root activity. They were significant higher than other 19 treatments. Soaking for 5 h in 50% biogas slurry had the highest content of chlorophyll a, chlorophyll b, chlorophyll (a + b) and ratio of chlorophyll a/ chlorophyll b. It was significant higher in these index, except b, than other 19 treatment. Soaking for 5 h in 25% biogas slurry had the lowest MDA content (0.0280 micromol x L(-1)), then was Soaking for 4 h in 50% biogas slurry (0.0286 micromol x L(-1) in MDA content).

CONCLUSIONAppropriate biogas slurry concentration combined with seed soaking time can improve the germination and growth of T. erecta. As a whole, soaking for 5 h in 50% biogas slurry had the best effects on germination and growth in seedling stage for T. erecta.

Biofuels ; Germination ; Immersion ; Seedlings ; anatomy & histology ; growth & development ; Seeds ; anatomy & histology ; growth & development ; Tagetes ; anatomy & histology ; growth & development ; Time Factors

Objective To investigate whether the percutaneous ethanol injection (PEI)under sedation and analgesia can in-crease the energy deposition and curative efficiency of the high intensity focused ultrsound(HIFU)in treating unresectable middle and advanced stages of primary liver cancer.Methods Thirty-six cases of clinically diagnosed unresectable middle and advanced sta-ges of primary liver cancer were randomly divided into the PEI+ HIFU group(combination group,n = 23)and the simple HIFU group (HIFU group,n=13);10mL of the mixture of 99.7% ethanol and iodized oil (9:1)was given by intratumoral injection at 30 min before ablation in the PEI+HIFU group,while 0.9% physiological saline 10mL was replaced in the simple HIFU group.The ablation energy efficiency factor(EEF)and irradiation time were compared between the two groups.Results The ablation EEF in the PEI+HIFU group and the simple HIFU group were (13.82+4.26)J/mm3 and (25.63+6.31)J/mm3 respectively,the PEI+HIFU group was significantly lower than the simple HIFU group (P <0.05);the irradiation time were (1 468.28+253.21)s and (2 352.56+463.34)s respectively;which in the PEI+ HIFU group was significantly shortened (P <0.05).Conclusion PEI can enhance the HIFU ablation energy deposition and improve the efficiency of HIFU for treating unresectable primary liver cancer.

KRAS is one of the most frequently mutated human oncogenes. In spite of mounting efforts on the development of direct or indirect inhibition targeting KRAS, little has been achieved because of insurmountable difficulties, titling KRAS "undruggable". Recently, subtype-specific inhibitors have shown great hope. Some KRAS^G12C inhibitors have entered clinical trials, including adagrasib and sotorasib, and have shown preliminary clinical effectiveness. Experiences from the inhibitors targeting the downstream factors of RAS pathways show that the anticancer activity of these drugs will be limited due to the development of drug resistance. Preclinical studies of KRAS^G12C inhibitors have revealed that the application of these agents might be hampered by the drug resistance issue. The current review aims to describe the current status of KRAS^G12C inhibitors, and discuss the mechanisms underlying KRAS^G12C inhibitor resistance, so as to provide the clues for the combat of drug resistance.

OBJECTIVETo study the effects and mechanism of hydrogen peroxide (H2O2) of low concentration on dynamic changes of intracellular free calcium contents ([Ca2+]i) in cultural rat liver oval cells (WB-F344 cells).

METHODSUsing Fluo-3/Am as fluorescent indicator of [Ca2+]i and it was measured by laser scanning confocal microscope system.

RESULTSThe results showed that: (1) A rapid transient spiking of [Ca2+]i occurred after the stimulation of H2O2 of low concentration (800 nmol/L). (2) The [Ca2+]i increase was abolished by pretreated with catalase (CAT) or by incubated in D-Hank's solution containing EGTA, the chelate of extracellular Ca2+. (3) The [Ca2+]i increase was not inhibited by pretreated nifedipine, Ca2+ channel blocker, but was abolished by pretreated with anthracere-9-cardoxylic acid (A9C), the Cl-channel blocker and which also blocked calcium activated non-selective cation channel (CAN).

CONCLUSIONSThese results suggest that the increase of [Ca2+]i induced by H2O2 of low concentration may be due to the influx of extracellular Ca2+ through CAN.

Animals ; Calcium ; metabolism ; Cells, Cultured ; Hepatocytes ; metabolism ; Hydrogen Peroxide ; pharmacology ; Ion Channels ; drug effects ; Microscopy, Confocal ; Rats

Pancreatic malignant tumor with more complex diagnosis and treatment is one of digestive system tmnors,especially pancreatic cancer (PC) continues to have high malignancy and poor curative effect and prognosis."Pancreas" conference is currently held every.two years,and it is acknowledgedas a distinguished gathering of the pancreatic tumor field through showing abundant leading-edge achievements.Authors summarized contents and features of the Pancreas 2018 conference sponsored by Johns Hopkins Hospital,and made some analyses based on translational medicine,evidence-based medicine,multidisciplinary team,new surgical technology and domestic teams' harvests,meanwhile,they also will disseminate and share leading-edge information with domestic doctors,and provide new ideas for diagnosis and treatment of PC and basic and clinical researches.

T,and 916-917 ins G were SLC26A4 mutations unreported hitherto, which may be specific to the Chinese population. CONCLUSION The EVA syndrome is a typical autosomal recessivehereditary disease caused by mutations in SLC26A4 gene. Genetic testing of SLC26A4 is the one of the important diagnostic methods for EVA syndrome.

Objective To elucidate the electrophysiological features of POEMS syndrome. Methods We retrospectively analyzed the electrophysiological findings of 22 patients of POEMS, and compared their results with those of 22 patients with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). Results Compared with the CIDP group, the motor nerve conduction velocity was decreased in the POEMS group, but the difference was not significantstatistically (P>0.05); whereas, distal motor latency (DML) was significantly decreased (P<0.05), and terminal latency index (TLI) was significantly increased (P<0.05). The incidence rate of the nerve conduction block in the POEMS group was lower than that in the CIDP group (P<0.05). Compound muscle action potential (CMAP) of the tibial nerve was decreased significantly in the POEMS group as compared with the CIDP group (P<0.05), whereas CMAP of the median nerve was not significantly different (P>0.05). Abnormal electrophysiology was frequently observed in muscles of lower limbs in the POEMS group, and in comparison of upper limbs, the difference was not significant statistically (P<0.05).Conclusion In POEMS syndrome, slowing of nerve conduction velocity is more predominant in the intermediate segments of the peripheral nerve, and conduction block is rare. Abnormal nerve conduction may be correlated with limbs.