Non-alcoholic fatty liver disease (NAFLD) is one of the most common chronic liver diseases. However, due to its complex pathogenesis, there are no officially approved drugs for NAFLD treatment currently. Therefore, it is extremely urgent to find safe and effective anti-NAFLD drugs. Nowadays, lipid-lowering drugs are the main option for NAFLD therapy, but the clinical efficacy of chemical drugs is also very limited, as well as the frequent side effects or adverse reactions. Traditional Chinese medicine (TCM) has attracted more and more attention in the treatment of NAFLD due to its unique advantages through multiple targets and pathways with few side effects. In recent years, numerous studies have demonstrated that the imbalance of gut microbiota plays an important role in the occurrence and development of NAFLD. This review systematically summarizes the experimental and clinical evidences of TCM active compounds and TCM prescription involved in the regulation of intestinal flora in the treatment of NAFLD in recent years, so as to provide a reference for further exploring the pathogenesis of NAFLD and exploring TCM treatment methods.

Objective To discuss the diagnosis and treatment of renal pelvic carcinoma associated with renal stone.Methods A total of 13 patients,aged from 49 to 73 years old and averaged 59years old.The history of renal stone was 16 years.13 patients accepted B ultrasound check and 1 was found soft tissue occupying.8 patients accepted IVU check and none was found soft tissue occupying.7 patients accepted CT scan and 4 were found soft tissue occupying.The fluorescence in situ hybridization (FISH) examination was done for 2 patients and both were positive.6 patients were found lesions at renal pelvis mucous membrane during the operation of percutaneous nephrolithotripsy,4 accepted radical operations of renal pelvic carcinoma and 2 patients accepted radical nephrectomy according to the biopsy pathology.4 were found soft tissue occupying before operation and accepted radical operation of renal pelvic carcinoma ultimately.1 patient suffered gross hematuria and renal insufficiency accepted the renal pelvic carcinoma vaporization under the ureteroscope.Results The pathology showed that 7 cases were transitional cell carcinoma,4 were transitional cell carcinoma combined squamous cell carcinoma (SCC) metaplasia and 2 were squamous cell carcinoma.6 of 8 patients' stone chemical composition were infection stone and 2 were calcic blended stone.3 patients were followed up 1 to 2 years and survival with no tumor recurrence.The tumor recurred 10 months of the patient accepted the operation of renal pelvic carcinoma vaporization and accepted vaporization again.1 patient bsuffered SCC and local lymph node metastasis.He died 13 months post-operation.Conclusions For the patient who had long history of stone,combining infection with symptoms of severe hematuria and postoperation hematuria,the possibility of renal pelvic carcinoma should be considered.CT scan and urine FISH may help for diagnosis.The biopsy should routinely perform for the doubtful mucosa lesion during the cavity stone operation.Early and timely diagnosis and operation is the key for the patients with pelvic carcinoma associated with renal stone.

Objective To investigate the expressions of Transforming Growth Factorβ2 (TGF-β2) and Smad3 in human gliomas associated with pathologic grading. Methods The expressions of TGFβ2 and Smad3 protein were detected with SP immunhistochemistry in 80 human glioma specimens. The Kapan-Meier survival curves of progression-free survival time and overall survival time in different expression levels was compared with log-rank. Results The expression of TGFβ2 and Smad3 correlated with the pathological grading (r=0.545, r=0.570, P<0.01). Both progression-free survival time and overall survival time were significantly different between low expression group and high expression group (P<0.05). Conclusion Both TGF-β2 and Smad3 correlate well with the occurrence and differentiation of human gliomas,which help for the diagnosis, treatment and prognosis judgment．

Objective:To investigate variety pattern of expression level of TCRV?subfamilies in mononuclear cell in spleen tissue of rats with dampness pathogenic factors and normal rats by using FQ-PCR technique. Methods:32 SD rats were divided into four groups: normal group, external dampness group, internal dampness group, external and internal dampness group. Observing period was 20 days. 3 Rats were randomly selected from each group in order to exam the TCRV? subfamilies expression level. Results:The expression of TCRV?1, TCRV?7, TCRV?9 and TCRV?13 in external dampness group were higher than those in normal group (P

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.

AIMTo set up an artificial neural network system and optimize by genetic algorithm (GA) to predict drug bioavailability.

METHODSGenetic algorithm was used to optimize weights of the artificial neural network. The optimal solution of the artificial neural network model at a specific condition was obtained using the good search ability of genetic algorithm in order to predict drug bioavailability. Volume, refractivity, lgP(c), hydration, polarizability, E(HOMO) and E(LUMO) are inputs of the drug bioavailability prediction neural network, and its output is average drug bioavailability.

RESULTSThe prediction precision of average drug bioavailability of the GA- neural network model is 95.9%.

CONCLUSIONThis model can be used in the forecasting of drug bioavailability.

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

Objective To investigate the effects of antihypertension and reversing left ventricular hypertro- phy by carvedilol or bisoprolol in patients with mild to moderate essential hypertension.Methods 40 cases of mild to moderate essential hypertension patients were selected for this random single-blind,paralleling controlled clinical study.Results Patients were randomized to take 12.5～25mg carvedilol tablet orlce daily or bisoprolol 2.5～5mg once daily if DBP was still in the range of 12.0～14.6kPa(90～110mmHg)after 2 weeks' placebo baseline. Carvedilol group included 20 cases,bisoprolol group included 20 cases,and the course was 24 weeks.Blood pressure and heart rate were measured and symptoms and signs were recorded.At the end of placebo and in 24 weeks heart ultrasound,blood routine,serum glucose,blood lipid,hepatic function and renal function were examined.SBP,DBP and heart rate of patients in two groups decreased obviously.There were significant differences between the two groups.Ventricular hypertrophy of carvedilol group improved than that in pretherapy.There were significant differ- ences between the two groups.Conclusion Carvedilol was well-tolerated with less side effects such as mild headache,tiredness,dizziness,slightly elevating of serum glucose.Carvedilol could well treat the mild moderate essen- tial hypertension effectively and safely by 12.5～25mg once daily.