A HPLC-MS/MS multiple-reaction monitoring (MRM) quantitative analysis was made to establish a determination method for drug concentrations of costunolide (Co) and dehydrocostuslactone (De) in blood samples in the positive ion mode, with diazepam as the internal standard substance, in order to study the pharmacokinetic process of sesquiterpene lactones costunolide and dehydrocostuslactone after the oral administration of Weichang'an pills, and provide an theoretical basis for further studies on the substance basis for the anti-diarrhea effect of Weichang'an pills. In the blood samples, Co and De showed a good linearity within concentration ranges 0.700 0-769.7, 2.510-956.0 μg x L(-1), respectively. The results of precision, stability and recovery experiences proved the stability and reliability of the plasma concentration determination method. After the oral administration, the concentrations of Co and De in plasma increased with the increase in dose, with T(max) between 10.65-12.98 h, indicating a long time to reach peak plasma concentrations; C(max) of costunolide and dehydrocostuslactone ranged between 3.750-5.450,15.34-44.52 μg x L(-1), respectively. The in vivo adsorption of Co and De conformed to the one-compartment model, with a longer time to attain the peak plasma concentrations. These results provided an experimental basis for revealing the active substance basis and clinical medication of Weichang'an pills.
Administration, Oral ; Animals ; Drugs, Chinese Herbal ; administration & dosage ; chemistry ; pharmacokinetics ; Lactones ; administration & dosage ; blood ; pharmacokinetics ; Male ; Rats ; Rats, Wistar ; Sesquiterpenes ; administration & dosage ; blood ; pharmacokinetics ; Tablets ; administration & dosage ; chemistry ; pharmacokinetics

Intraperitoneal administration of timosaponin A-III (TA-III) has therapeutic effects on high-fat diet-induced metabolic dysfunction-associated steatotic liver disease (MASLD), but oral administration has no effect. This suggests that gut microbiota may affect the oral bioavailability of TA-III. Metabolic dysfunction-associated steatohepatitis (MASH) is an inflammatory subtype of MASLD. To investigate the therapeutic effect of different administration modes of TA-III on MASH and its relationship with gut microbiota metabolism. In this study, a MASH mouse model was induced by choline-deficient, L-amino acid-defined, high-fat diet (CDAHFD). Comparing the therapeutic effect of intraperitoneal injection (10 mg·kg^-1, ip) and intragastric administration (100 mg·kg^-1, ig) of TA-III. The concentration of TA-III in serum of rats under the two administration modes was analyzed. On this basis, the metabolic effect of gut microbiota on TA-III in mice was verified by the experiment of metabolism of gut microbiota in vitro. The pharmacokinetic experiment of combined antibiotic intervention in mice further verified the metabolism of TA-III by gut microbiota in mice. Finally, the concentration of TA-III in serum of mice after the administration of TA-III by intragastric administration under different antibiotic intervention conditions was compared, and 16S rRNA sequencing analysis was combined to find the key bacteria that may participate in the metabolism of TA-III. The animal welfare and experimental procedures in this paper were in accordance with the provisions of the Animal Ethics Committee of Shanghai University of Traditional Chinese Medicine. The ethics approval number is PZSHUTCM2307030004 and PZSHUTCM2310200003. The results showed that TA-III (10 mg·kg^-1, ip) had definite therapeutic effect on MASH mice, but TA-III (100 mg·kg^-1, ig) was ineffective. The analysis showed that the prototype concentration of TA-III in serum and liver of mice in TA-III (100 mg·kg^-1, ig) was significantly lower than TA-III (10 mg·kg^-1, ip), suggesting that the oral administration of TA-III may be metabolized by gut microbiota. The concentration of TA-III in serum of streptomycin (Str) treated mice was higher than normal mice. Combined with 16S rRNA gene sequencing analysis, it was found that the abundance of Akkermansia_muciniphila (A. muciniphila) was significantly reduced in the Str group. In vitro experiments showed that A. muciniphila could metabolize TA-III. In conclusion, gut microbiota is an important factor affecting the efficacy of TA-III administration through the gastrointestinal tract, in which A. muciniphila may play an important role.

Objective To explore the clinical,radiological findings and pathogenic factor of spondylometaphyseal dysplasia.Methods Five cases were reported and the relevant documents were studied retrospectively.Plain X-ray film was performed in all patients.Results There were 4 male and 1 female,age ranged from 4 to 15 years with average of 9 years.The main features of 5 cases included delayed bone age,stature short,short trunk,waddling gait noted,scoliosis in 2 cases,kyphoscoliosis in 1 case,severe genu valgum in 2 cases.The main X-ray appearance of 5 cases is multiple irregularities of long bones metaphyses associated with platyspondylia,epiphysis is normal.Type Ⅰ SMD in 2 cases,Type Ⅱ SMD in 1 case,Type Ⅲ SMD in 2 cases.Conclusion When we meet children with delayed bone age and stature short,and muhiple irregularities of long bones metaphyses associated with platyspondylia were seen in X-ray plain film.we should think about spondylometaphyseal dysplasia.

Humans ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/diagnosis* ; Death, Sudden/etiology*

OBJECTIVETo evaluate the application of temporal fascia flaps in the correction of severe depression deformities at lower eyelids.

METHODSSevere depression deformities at lower eyelid were corrected with temporal fascia flaps pedicled with superficial temporal artery in 9 cases.

RESULTSAll flaps survived with good appearance. All patients were followed up for 6-12 months with good long-term results. The donor sites had no obvious scalp scar.

CONCLUSIONSTemporal fascia flap is an optimal choice for correction of the severe depression deformities at lower eyelid. It is easily performed with good result and less donor site morbidity.

Adolescent ; Adult ; Blepharoplasty ; methods ; Eyelids ; abnormalities ; surgery ; Female ; Follow-Up Studies ; Humans ; Male ; Reconstructive Surgical Procedures ; methods ; Skin Transplantation ; Surgical Flaps ; Young Adult

OBJECTIVETo develop a RP-HPLC method to determine plumbagin in Plumbago zeylanica, and to investigate contents of plumbagin in different parts of. P. zeylanica.

METHODThe analysis was carried out at 30 degrees C on a Kromasil C18, column eluted with a mobile phase consisting of a mixture of methanol-water (65: 35). The flow rate was 1 mL x min(-1), the detector wavelength was 213 nm.

RESULTThe calibration curve was linear within the concentration ranges of 0.020 8-0. 104 microg (r = 0. 9999). The average recovery was 98.7%. The contents in the root, stem and leaf were 0.394 5%, 0.050 8%, 0.031 4% respectively.

CONCLUSIONThis method is simple, accurate, replicate and suitable for the determination of plumbagin in P. zeylanica.

Chromatography, High Pressure Liquid ; methods ; Naphthoquinones ; analysis ; Plant Leaves ; chemistry ; Plant Roots ; chemistry ; Plant Stems ; chemistry ; Plants, Medicinal ; chemistry ; Plumbaginaceae ; chemistry ; Quality Control ; Reproducibility of Results

Objective To analyze the different risks of cardia neoplasms in the immediate relatives of the cardia cancer patients,through a case-control study.Methods A case-control study was adopted on 772 cases and 772 controls,and relative risk (RR) were measured to compare the results from patemal or matrilineal groups.Results (1)Risk of the 1st grade kinship to the male cardia-cancer-patient group was obviously higher than that of the control group with RR=2.61 (95％CI:1.44-4.73,P＜0.01).(2) The risks of both paternal (P＜0.05) and matrilineal (P＜0.05) in the male cardia-cancer-patients were obviously higher than that of the control groups while the risk of those male cardia-cancer-patients in the paternal was higher than that of the control group (P＜0.05),so as the case for female patients in the matrilineal group (P＜0.05).(3) Data from the 1st grade kinship of cardia-cancer-patient group showed that parents and siblings had a higher risk than the control group (P＜0.05).(4) No significant genetic differences were found between the patemal of either the cancer group or the control group (P＞ 0.05),but statistical difference was observed that the risk of someone being the matrilineal of the cancer group was higher than that of the control group (P＜0.05).Conclusion The risks of cardia-cancer were higher in the 1st grade kinship,which including parents,brothers,sisters,maternal grandmother,mother,and maternal aunt.It was suggested that prevention programs should be focused on both earlier detection and treatment of the patients.New strategy for cancer prevention also need to be further developed.

Objective To explore the relationship between esophagus cancer patients and both environmental and genetic factors,through analyzing the data on birth orders from esophagus cancer patients of Shanxi province.Methods Both Greenwood and Haldane methods on birth order were used to study the 1101 cases with esophagus cancer from Shanxi province.All the patients had received surgery and were diagnosed,by pathological evidence.First certificates of the patients were confirmed through the standard genetic epidemiologic investigation.Birth order was investigated on probands of the 1101 cases with esophagus cancer and their 44 siblings.Results Results form the Greenwood method showed that there was a tendency for cases with esophagus cancer in birth orders First to Third.However,the Haldane method showed that the results were quite different between actual value and the average theory value of 6A (6A(actual value)=17 118,(X)6A(average theory value) =19 290,X=∣6A-(X)6A∣/√V6A =7.63,X ＞ 2) which suggested that the birth order had some effects on the occurrence of esophagus cancer.In addition,the actual value of 6A was lower than the theoretic average value,and the parents at younger productive age or baby at the first birth was easy to develop esophagus cancer.Conclusion Esophagus cancer was related with the birth order,especially at early order,which was not consistent with the national reports on esophagus cancer.Results from this study suggested that there were certain effects of environmental risk factors on esophagus cancer patients.

Adult ; Humans ; Leukocytes, Mononuclear ; metabolism ; Lupus Erythematosus, Systemic ; genetics ; Proto-Oncogene Protein c-ets-1 ; genetics ; Reverse Transcriptase Polymerase Chain Reaction

This study was aimed to investigate the expression of c-FLIPL, c-FLIPS and DLK1 mRNA in the patients with myelodysplastic syndrome (MDS) and its clinical significance. The mRNA expression of c-FLIPL, c-FLIPS and DLK1 in bone marrow mononuclear cells (BMMNC) of 16 patients with MDS and 3 controls were detected by RT-PCR. The results indicated that the expression of DLK1 mRNA was up-regulated in MDS, including RA and RAEB, as compared with controls (p < 0.05). There was no significant difference in expression of DLK1 between RA and RAEB patients (p > 0.05); the expression of c-FLIPL mRNA both in RA and RAEB patients was higher than that in controls (p < 0.05). There was no significant difference in expression of c-FLIPL between RA and RAEB patients (p > 0.05); the expression of c-FLIPS mRNA was not significantly different between MDS patients and controls (p > 0.05), but its expression in RAEB patients was significantly higher as compared with RA patients and controls (p < 0.05). It is concluded that the mRNA expressions of DLK1, c-FLIPL and c-FLIPS in MDS patients are abnormal, some of which may be useful as an important indicator for the evaluation of development in MDS.
Aged ; Bone Marrow Cells ; metabolism ; CASP8 and FADD-Like Apoptosis Regulating Protein ; genetics ; metabolism ; Case-Control Studies ; Female ; Gene Expression ; Humans ; Intercellular Signaling Peptides and Proteins ; genetics ; metabolism ; Male ; Membrane Proteins ; genetics ; metabolism ; Myelodysplastic Syndromes ; genetics ; RNA, Messenger ; genetics